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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT03891524
Registration number
NCT03891524
Ethics application status
Date submitted
25/03/2019
Date registered
27/03/2019
Titles & IDs
Public title
A Study of JNJ-70033093 (BMS-986177) Versus Subcutaneous Enoxaparin in Participants Undergoing Elective Total Knee Replacement Surgery
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Scientific title
A Randomized, Open-Label, Study Drug-Dose Blind, Multicenter Study to Evaluate the Efficacy and Safety of JNJ-70033093 (BMS-986177), an Oral Factor XIa Inhibitor, Versus Subcutaneous Enoxaparin in Subjects Undergoing Elective Total Knee Replacement Surgery
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Secondary ID [1]
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70033093THR2001
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Secondary ID [2]
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CR108600
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Universal Trial Number (UTN)
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Trial acronym
AXIOMATIC-TKR
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Arthroplasty, Replacement, Knee
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Condition category
Condition code
Skin
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Dermatological conditions
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Skin
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0
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Other skin conditions
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Inflammatory and Immune System
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0
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Other inflammatory or immune system disorders
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Cancer
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Malignant melanoma
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Cancer
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Brain
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - JNJ-70033093 25 mg
Treatment: Drugs - JNJ-70033093 50 mg
Treatment: Drugs - JNJ-70033093 100 mg
Treatment: Drugs - JNJ-70033093 200 mg
Treatment: Drugs - Placebo
Treatment: Drugs - Enoxaparin 40 mg
Experimental: Group A: JNJ-70033093 25 mg + Placebo BID - Participants will receive JNJ-70033093 25 milligram (mg) (1\*25 mg capsule) and 1 placebo capsule twice daily (BID), orally for 10 to 14 postoperative days.
Experimental: Group B: JNJ-70033093 50 mg BID - Participants will receive JNJ-70033093 50 mg (2\*25 mg capsules) BID orally for 10 to 14 postoperative days.
Experimental: Group C: JNJ-70033093 100 mg + Placebo BID - Participants will receive JNJ-70033093 100 mg (1\*100 mg capsule) and 1 placebo capsule BID orally for 10 to 14 postoperative days.
Experimental: Group D: JNJ-70033093 200 mg BID - Participants will receive JNJ-70033093 200 mg (2\*100 mg capsules) BID orally for 10 to 14 postoperative days.
Experimental: Group E: JNJ-70033093 25 mg Once Daily + Placebo - Participants will receive JNJ-70033093 25 mg (1\*25 mg capsule) once daily and 1 placebo capsule in the morning and 2 placebo capsules in the evening, orally for 10 to 14 postoperative days.
Experimental: Group F: JNJ-70033093 200 mg Once Daily + Placebo - Participants will receive JNJ-70033093 200 mg (2\*100 mg capsules in the morning) once daily and 2 placebo capsules in the evening, orally for 10 to 14 postoperative days.
Experimental: Group G: JNJ-70033093 50 mg once daily + Placebo - Participants will receive JNJ-70033093 50 mg (2\*25 mg capsules in the morning) once daily and 2 placebo capsules in the evening, orally for 10 to 14 postoperative days.
Active comparator: Group I: Enoxaparin 40 mg Once Daily - Participants will receive enoxaparin 40 mg once daily subcutaneously for 10 to 14 postoperative days.
Treatment: Drugs: JNJ-70033093 25 mg
Participants will receive JNJ-70033093 25 mg (1\*25 mg capsule) BID (in Group A) or once daily (in Group E), orally for 10 to 14 postoperative days.
Treatment: Drugs: JNJ-70033093 50 mg
Participants will receive JNJ-70033093 50 mg (2\*25 mg capsules) BID orally for 10 to 14 postoperative days.
Treatment: Drugs: JNJ-70033093 100 mg
Participants will receive JNJ-70033093 100 mg (1\*100 mg capsule) BID, orally for 10 to 14 postoperative days.
Treatment: Drugs: JNJ-70033093 200 mg
Participants will receive JNJ-70033093 200 mg (2\*100 mg capsules) BID (in Group D) or once daily (in Group F), orally for 10 to 14 postoperative days.
Treatment: Drugs: Placebo
Participants will receive placebo matching to JNJ-70033093, orally.
Treatment: Drugs: Enoxaparin 40 mg
Participants will receive enoxaparin 40 mg once daily subcutaneously for 10 to 14 postoperative days.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Number of Participants With Total Venous Thromboembolism (VTE) (CEC-adjudicated)
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Assessment method [1]
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Total VTE was defined as the composite of clinical events committee (CEC)-adjudicated proximal and/or distal Deep Vein Thrombosis (DVT) (asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic), nonfatal pulmonary embolism (PE), or any death.
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Timepoint [1]
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Up to Day 14
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Primary outcome [2]
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Number of Participants With Dose Limiting Toxicities (DLTs): Safety Lead-in (SLI) Phase
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Assessment method [2]
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DLT: any adverse event (AE) or laboratory abnormality not explained by underlying disease/disease progression/intercurrent illness/concomitant therapies/resulting in inability to tolerate 75% of planned dose of binimetinib or encorafenib during Cycle 1. Left ventricular ejection fraction (LVEF) \>10%, Grade (G)\>=3 cardiac disorders; G3/4 hypertension vascular disorders; G3/4 rash, hand foot skin reaction, photosensitivity; G3/4 diarrhea, nausea/vomiting Total bilirubin (TBL) G\>=3 (\>3.0\*upper limit of normal \[ULN)\]);AST/ALT\>5-8\*ULN\>5 days,\>8\*ULN,\>3\*ULN concurrent TBL\>2\*ULN;G\>=3 serum creatinine, CK elevation, ECG QTcF prolonged,G3 troponin, electrolyte\>72 hours,G3/4 amylase/lipase.G4 ANC, platelet count\>7 days;G3/4 platelet count, other AE except lymphopenia. G\>=3 retinopathy, other disorder\>21 days; G2 uveitis/eye pain/blurred vision/decreased visual acuity; G4 other disorder; Other hematologic/non hematologic G\>=3 AE. This outcome measure was planned to be analyzed in SLI phase only.
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Timepoint [2]
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Cycle 1 of SLI phase (up to 28 days)
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Primary outcome [3]
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Number of Participants With Treatment Emergent Adverse Events Graded by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI _CTCAE) Version (v) 4.03: SLI Phase
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Assessment method [3]
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AE: any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs: events between first dose of study drug up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state or start of subsequent anticancer drug therapy minus 1 day, whichever occurred first. Grades by NCI CTCAE v.4.03: Grade 1= asymptomatic or mild , clinical or diagnostic observations only, intervention not indicated; Grade 2= moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3= severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4= life-threatening consequence, urgent intervention indicated; Grade 5= death related to AE. Number of participants with AEs per maximum grades were reported.
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Timepoint [3]
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Day 1 of dosing up to 30 days after last dose of study drug in SLI Phase, maximum duration up to 10.4 months
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Primary outcome [4]
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Number of Participants With Hepatology Laboratory Test Abnormalities: SLI Phase
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Assessment method [4]
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Hepatology laboratory abnormalities included following parameters: alanine aminotransferase (ALT), aspartate aminotransferase (AST), ALT or AST greater than or equal to (\>=) 3\*upper limit normal (ULN), \>=5\*ULN, \>=10\*ULN, \>=20\*ULN; total bilirubin (TBILI): \>=2\*ULN; ALT \>=3\*ULN and TBILI \>=2\*ULN; AST \>=3\*ULN and TBILI \>=2\*ULN; ALT or AST \>=3\*ULN and TBILI \>=2\*ULN; ALT or AST \>=3\*ULN and TBILI \>=2\*ULN and ALP \>2\*ULN; ALT or AST \>=3\*ULN and TBILI \>=2\*ULN and ALP \<=2\*ULN or missing. Only those laboratory test parameters in which at least 1 participant had data were reported.
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Timepoint [4]
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Baseline (Day 1) up to 30 days after last dose of study drug in SLI Phase, maximum duration up to 10.4 months
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Primary outcome [5]
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Number of Participants With Shift From Baseline for Hematology and Coagulation Laboratory Test Abnormalities Based on NCI-CTCAE v4.03: SLI Phase
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Assessment method [5]
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Hematology and coagulation laboratory test included: activated partial thromboplastin time prolonged, anemia, hemoglobin increased, international normalized ratio (INR) increased, leukocytosis, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased, and white blood cell decreased. Laboratory results were categorically summarized according to the NCI-CTCAE criteria v4.03. Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Grade 0 was assigned for all non-missing values not graded as 1 or higher per CTCAE criteria. Number of participants with shift from baseline for hematology and coagulation laboratory test were assessed. Only those laboratory test parameters in which at least 1 participant had data were reported.
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Timepoint [5]
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Baseline (Day 1) up to 30 days after last dose of study drug in SLI Phase, maximum duration up to 10.4 months
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Primary outcome [6]
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Number of Participants With Shift From Baseline for Biochemistry Laboratory Test Abnormalities Based on NCI-CTCAE v4.03: SLI Phase
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Assessment method [6]
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Biochemistry laboratory test included: alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, creatine kinase (CK) increased, creatinine increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia, lipase increased, and serum amylase increased. Laboratory results were categorically summarized according to the NCI-CTCAE criteria v4.03. Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Grade 0 was assigned for all non-missing values not graded as 1 or higher per CTCAE criteria. Number of participants with shift from baseline for biochemistry laboratory test were assessed. Only those laboratory test parameters in which at least 1 participant had data were reported.
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Timepoint [6]
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Baseline (Day 1) up to 30 days after last dose of study drug in SLI Phase, maximum duration up to 10.4 months
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Primary outcome [7]
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Number of Participants With Notable Abnormal Vital Signs: SLI Phase
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Assessment method [7]
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Vital signs included: systolic and diastolic blood pressure (BP),pulse rate,weight and temperature.Systolic and diastolic BP was measured in millimeters of mercury (mmHg) based on criteria:High Systolic BP:\>=160 mmHg and increase \>=20 mmHg from baseline;High Diastolic BP:\>=100 mmHg and increase\>=15 mmHg from baseline;Low Systolic BP:\<=90 mmHg with decrease from baseline of \>=20 mmHg;Low Diastolic BP:\<=50 mmHg with decrease from baseline of \>=15 mmHg;Pulse rate was measured in beats per minute (bpm) based on criteria:High pulse rate \>=120 bpm with increase from baseline of \>=15 bpm;Low pulse rate \<=50 bpm with decrease from baseline of \>=15 bpm;Weight was measured in in kilogram (kg) based on criteria:Increase from baseline of \>=10%,:\>=20% decrease from baseline;Temperature was measured in degree Celsius (C) based on criteria:High body temperature \>=37.5 degree C,Low body temperature \<=36 degree C.Only those vital signs parameters in which at least 1 participant had data were reported.
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Timepoint [7]
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Baseline (Day 1) up to 30 days after last dose of study drug in SLI Phase, maximum duration up to 10.4 months
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Primary outcome [8]
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Number of Participants With Notable Abnormal Electrocardiogram (ECG) Values: SLI Phase
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Assessment method [8]
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In this outcome measure, number of participants with notable abnormal ECG values included: Fridericia's Correction Formula (QTcF) values in millisecond (msec) based on following criteria: 1) Increase from baseline \>30 msec; 2) Increase from baseline \>60 msec; 3) New \>450 msec; 4) New \>480 msec; and 5) New \>500 msec; heart rate values in bpm based on following criteria: 1) Increase from baseline \>25% and to a value \>100; 2) Decrease from baseline \>25% and to a value \<50. Only those ECG parameters in which at least 1 participant had data were reported.
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Timepoint [8]
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Baseline (Day 1) up to 30 days after last dose of study drug in SLI Phase, maximum duration up to 10.4 months
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Primary outcome [9]
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Number of Participants With Incidence of Dose Interruptions, Dose Modifications and Discontinuations Due to AEs: SLI Phase
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Assessment method [9]
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An AE is any untoward medical occurrence in clinical investigation participant administered a product or medical device; event need not necessarily to have a causal relationship with treatment or usage. In this outcome measure, number of participants with incidence of dose interruptions, dose modifications and discontinuations due to AEs were reported.
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Timepoint [9]
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Baseline (Day 1) up to 30 days after last dose of study drug in SLI Phase, maximum duration up to 10.4 months
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Primary outcome [10]
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Brain Metastasis Response Rate (BMRR) Based on Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (mRECIST v1.1): Phase 2
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Assessment method [10]
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BMRR was reported in terms of percentage of participants who achieved a confirmed best overall response (BOR) of confirmed complete response (CR) or partial response (PR) in brain metastasis per mRECIST v1.1 from date of first dose until disease progression, death due to any cause, or start of subsequent anticancer therapy, whichever occurred first. BOR: best response recorded from date of first dose of study treatment until progression by investigator assessment at each time point. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
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Timepoint [10]
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From date of first dose until disease progression, death due to any cause or subsequent therapy initiation, whichever occurred first in Phase 2 (approximately up to 8.3 months)
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Secondary outcome [1]
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Number of Participants With Any Bleeding Event (CEC-adjudicated)
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Assessment method [1]
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Any bleeding was defined as the composite of major bleeding according to the International Society on Thrombosis and Haemostasis (ISTH) criteria modified for the surgical setting, clinically relevant nonmajor bleeding events, or minimal bleeding events as assessed by the CEC.
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Timepoint [1]
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Up to Day 14; Up to Day 52
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Secondary outcome [2]
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Number of Participants With Total VTE (CEC-adjudicated)
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Assessment method [2]
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Total VTE was defined as the composite of (CEC-adjudicated) proximal and/or DVT (asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic), nonfatal PE, or any death.
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Timepoint [2]
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Up to Day 52
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Secondary outcome [3]
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Number of Participants With Composite of Major and Clinically Relevant Nonmajor Bleeding (CRNM) Events (CEC-adjudicated)
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Assessment method [3]
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Composite of Major bleeding event (BE): Fatal bleeding; bleeding that is symptomatic and occurs in critical area/organ and/or; extrasurgical site bleeding causing fall in Hemoglobin (Hb) level of 20 grams per liter (g/L) or more, or leading to transfusion of 2 or more units of whole blood or red cells with temporal association within 24-48 hours to bleeding, and/or; surgical site bleeding that requires second intervention open, arthroscopic, endovascular,or hemarthrosis resulting in prolonged hospitalization, deep wound infection and/or either unexpected and prolonged and/or sufficiently large to cause hemodynamic instability. CRNM bleeding: acute clinically overt bleeding that does not satisfy additional criteria required for bleeding event to be defined as major BE is still considered clinically relevant for example: Epistaxis, Gastrointestinal bleed,Hematuria,Bruising/ecchymosis,Hemoptysis,Hematoma.
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Timepoint [3]
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Up to Day 14, Up to Day 52
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Secondary outcome [4]
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Number of Participants With Major Bleeding Events (CEC-adjudicated)
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Assessment method [4]
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Number of participants with major BE (adjudicated by CEC) were reported. Major Bleeding events were defined as: fatal bleeding; bleeding that is symptomatic and occurs in critical area/organ and/or; extrasurgical site bleeding causing fall in Hb level of 20 g/L or more, or leading to transfusion of 2 or more units of whole blood or red cells with temporal association within 24-48 hours to bleeding, and/or; requires second intervention open, arthroscopic, endovascular, or hemarthrosis resulting in prolonged hospitalization or a deep wound infection and/or; either unexpected and prolonged and/or sufficiently large to cause hemodynamic instability.
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Timepoint [4]
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Up to Day 14; Up to Day 52
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Secondary outcome [5]
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Number of Participants With CRNM Bleeding Events (CEC-adjudicated)
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Assessment method [5]
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Number of participants with CRNM bleeding events (adjudicated by CEC) were reported. CRNM bleeding: acute clinically overt bleeding that does not satisfy additional criteria required for bleeding event to be defined as major BE is still considered clinically relevant for example: epistaxis, gastrointestinal bleed, hematuria, bruising/ecchymosis, hemoptysis, hematoma.
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Timepoint [5]
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Up to Day 14; Up to Day 52
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Secondary outcome [6]
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Number of Participants With Minimal Bleeding Events (CEC-adjudicated)
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Assessment method [6]
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Number of participants with minimal bleeding events (adjudicated by CEC) were reported. Minimal bleeding event was defined as any bleeding event not met major or CRNM criteria. CRNM bleeding: acute clinically overt bleeding that does not satisfy additional criteria required for bleeding event to be defined as major BE is still considered clinically relevant for example: epistaxis, gastrointestinal bleed, hematuria, bruising/ecchymosis, hemoptysis, hematoma.
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Timepoint [6]
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Up to Day 14; Up to Day 52
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Secondary outcome [7]
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Number of Participants With Major or CRNM Bleeding Events (CEC-adjudicated)
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Assessment method [7]
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Major Bleeding events were defined as: fatal bleeding; bleeding that is symptomatic and occurs in critical area/organ and/or; extrasurgical site bleeding causing fall in Hb level of 20 g/L or more, or leading to transfusion of 2 or more units of whole blood or red cells with temporal association within 24-48 hours to bleeding, and/or; requires second intervention open, arthroscopic, endovascular, or hemarthrosis resulting in prolonged hospitalization or a deep wound infection and/or; either unexpected and prolonged and/or sufficiently large to cause hemodynamic instability. CRNM bleeding: acute clinically overt bleeding that does not satisfy additional criteria required for bleeding event to be defined as major BE is still considered clinically relevant for example: epistaxis, gastrointestinal bleed, hematuria, bruising/ecchymosis, hemoptysis, hematoma.
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Timepoint [7]
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Up to Day 14; Up to Day 52
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Secondary outcome [8]
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Number of Participants With Major VTE (CEC-adjudicated)
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Assessment method [8]
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Number of participants with major VTE (adjudicated by CEC) were reported. Major VTE was defined as a composite of proximal DVT (asymptomatic confirmed by venography or objectively confirmed symptomatic), nonfatal PE, or any death.
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Timepoint [8]
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0
Up to Day 52
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Secondary outcome [9]
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0
Number of Participants With Major VTE (CEC-adjudicated)
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Assessment method [9]
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Number of participants with major VTE (adjudicated by CEC) were reported. Major VTE was defined as a composite of proximal DVT (asymptomatic confirmed by venography or objectively confirmed symptomatic), nonfatal PE, or any death.
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Timepoint [9]
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Up to Day 14
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Secondary outcome [10]
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Number of Participants With Proximal Deep Vein Thrombosis (DVT) (CEC-adjudicated)
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Assessment method [10]
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Number of participants with proximal DVT (adjudicated by CEC) were reported. DVT asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic.
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Timepoint [10]
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0
Up to Day 14
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Secondary outcome [11]
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Number of Participants With Proximal DVT (CEC-adjudicated)
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Assessment method [11]
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Number of participants with proximal DVT (CEC-adjudicated) were reported. DVT asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic.
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Timepoint [11]
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Up to Day 52
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Secondary outcome [12]
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Number of Participants With Distal DVT (CEC-adjudicated)
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Assessment method [12]
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Number of participants with distal DVT (CEC-adjudicated) were reported. DVT asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic.
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Timepoint [12]
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0
Up to Day 14
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Secondary outcome [13]
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0
Number of Participants With Distal DVT (CEC-adjudicated)
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Assessment method [13]
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Number of participants with distal DVT (adjudicated by CEC) were reported. DVT asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic.
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Timepoint [13]
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0
Up to Day 52
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Secondary outcome [14]
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Number of Participants With Nonfatal Pulmonary Embolism (PE) (CEC-adjudicated)
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Assessment method [14]
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Number of participants with nonfatal PE (adjudicated by CEC) were reported.
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Timepoint [14]
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0
Up to Day 14
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Secondary outcome [15]
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0
Number of Participants With Nonfatal Pulmonary Embolism (PE) (CEC-adjudicated)
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Assessment method [15]
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0
Number of participants with nonfatal PE (adjudicated by CEC) were reported.
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Timepoint [15]
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0
Up to Day 52
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Secondary outcome [16]
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0
Number of Participants With Deaths (CEC-adjudicated)
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Assessment method [16]
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0
Number of participants with deaths (CEC-adjudicated) were reported.
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Timepoint [16]
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Up to Day 14
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Secondary outcome [17]
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0
Number of Participants With Deaths (CEC-adjudicated)
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Assessment method [17]
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Number of participants with deaths (CEC-adjudicated) were reported.
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Timepoint [17]
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0
Up to Day 52
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Secondary outcome [18]
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0
Apparent Clearance (CL/F) of JNJ-70033093
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Assessment method [18]
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0
Apparent clearance of a drug was defined as a measure of the rate at which a drug got metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.
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Timepoint [18]
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0
Up to Day 14
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Secondary outcome [19]
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Apparent Volume of Distribution (V/F) of JNJ-70033093
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Assessment method [19]
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V/F was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug.
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Timepoint [19]
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0
Up to Day 14
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Secondary outcome [20]
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Impact of Selected Demographics: Apparent Clearance (CL/F) Based on Sex
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Assessment method [20]
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0
Impact of demographic character (sex) on CL/F was assessed.
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Timepoint [20]
0
0
Up to Day 14
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Secondary outcome [21]
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0
Impact of Selected Demographic: Age on CL/F
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Assessment method [21]
0
0
Impact of age on CL/F was assessed.
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Timepoint [21]
0
0
Up to Day 14
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Secondary outcome [22]
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0
Impact of Selected Demographic: Weight on CL/F
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Assessment method [22]
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0
Impact of weight on CL/F was assessed.
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Timepoint [22]
0
0
Up to Day 14
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Secondary outcome [23]
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0
Impact of Selected Laboratory Values: Renal Function on CL/F
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Assessment method [23]
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0
Impact of renal function on CL/F was assessed. The outcome measure was reported based on CRCL.
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Timepoint [23]
0
0
Up to Day 14
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Secondary outcome [24]
0
0
Impact of Selected Demographics: Sex on Apparent Volume of Distribution (V/F)
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Assessment method [24]
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0
Impact of sex on V/F was assessed.
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Timepoint [24]
0
0
Up to Day 14
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Secondary outcome [25]
0
0
Impact of Selected Demographics : Age on V/F
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Assessment method [25]
0
0
Impact of age on V/F was assessed.
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Timepoint [25]
0
0
Up to Day 14
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Secondary outcome [26]
0
0
Impact of Selected Demographics : Weight on V/F
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Assessment method [26]
0
0
Impact of weight on V/F was assessed.
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Timepoint [26]
0
0
Up to Day 14
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Secondary outcome [27]
0
0
Impact of Selected Laboratory Values: Renal Function on V/F
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Assessment method [27]
0
0
Impact of renal function on V/F was assessed. The outcome measure is reported based on CRCL.
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Timepoint [27]
0
0
Up to Day 14
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Secondary outcome [28]
0
0
Trend Test for Primary Efficacy Event Rate (CEC Adjudicated) by Multiple Comparison Procedure - Modelling (MCP-Mod) Approach
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Assessment method [28]
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The dose-response trend test based on the MCP-Mod framework consisted of contrast tests defined by prespecified candidate models (4 Emax dose-response models with varying degrees of ED50). Each model was evaluated for significance of trend, based on its optimal contrast, resulting in four t-test statistics, one for each candidate model. The t-test statistics were adjusted for the fact that 4 candidate models were included in the trend testing. The dose response of the drug was then established if the maximum of the t-test statistics exceeded the 95th percentile critical value. Here 'number' signifies the estimated response rate.
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Timepoint [28]
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0
Up to 14 days
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Secondary outcome [29]
0
0
Trend Test for the Composite of On-Treatment Major and Clinically Relevant Nonmajor Bleeding (CEC Adjudicated) by MCP-Mod Approach
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Assessment method [29]
0
0
The dose-response trend test based on the MCP-Mod framework consisted of contrast tests defined by prespecified candidate models (4 Emax dose-response models with varying degrees of ED50). Each model was evaluated for significance of trend, based on its optimal contrast, resulting in four t-test statistics, one for each candidate model. The t-test statistics were adjusted for the fact that 4 candidate models were included in the trend testing. The dose response of the drug was then established if the maximum of the t-test statistics exceeded the 95th percentile critical value. Here 'number' signifies the estimated response rate.
Query!
Timepoint [29]
0
0
Up to 14 days
Query!
Secondary outcome [30]
0
0
Extracranial Response Rate Based on RECIST v1.1: SLI Phase and Phase 2
Query!
Assessment method [30]
0
0
Extracranial response rate was defined as the percentage of participants with a BOR of confirmed CR or confirmed PR in extracranial lesions by investigator assessment per RECIST v1.1. BOR: best response recorded from date of first dose of study treatment until progression by investigator assessment at each time point. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Query!
Timepoint [30]
0
0
From date of first dose until disease progression, death due to any cause or subsequent therapy initiation, whichever occurred first in SLI Phase (approximately up to 10.4 months) and Phase 2 (approximately up to 8.3 months)
Query!
Secondary outcome [31]
0
0
Global Response Rate: SLI Phase and Phase 2
Query!
Assessment method [31]
0
0
Global response rate was defined as the percentage of participants with a BOR of confirmed CR or confirmed PR by investigator assessment in brain metastasis and extracranial lesions per combined mRECIST v1.1 and RECIST v1.1, respectively. BOR: best response recorded from date of first dose of study treatment until progression by investigator assessment at each time point. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum of the diameters (e.g., percent change from baseline).
Query!
Timepoint [31]
0
0
From date of first dose until disease progression, death due to any cause or subsequent therapy initiation, whichever occurred first in SLI Phase (approximately up to 10.4 months) and Phase 2 (approximately up to 8.3 months)
Query!
Secondary outcome [32]
0
0
Disease Control Rate (DCR) for Brain Metastasis Response Based on mRECIST v1.1: SLI Phase and Phase 2
Query!
Assessment method [32]
0
0
DCR was defined as the percentage of participants with a BOR of CR, PR or stable disease (SD) by Investigator assessment per mRECIST v1.1. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters recorded since the treatment started.
Query!
Timepoint [32]
0
0
From date of first dose until disease progression, death due to any cause or subsequent therapy initiation, whichever occurred first in SLI Phase (approximately up to 10.4 months) and Phase 2 (approximately up to 8.3 months)
Query!
Secondary outcome [33]
0
0
DCR for Extracranial Response Based on RECIST v1.1: SLI Phase and Phase 2
Query!
Assessment method [33]
0
0
DCR was defined as the percentage of participants with a BOR of CR, PR or SD by Investigator assessment per RECIST v1.1. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum demonstrates an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression.
Query!
Timepoint [33]
0
0
From date of first dose until disease progression, death due to any cause or subsequent therapy initiation, whichever occurred first in SLI Phase (approximately up to 10.4 months) and Phase 2 (approximately up to 8.3 months)
Query!
Secondary outcome [34]
0
0
DCR for Global Response: SLI Phase and Phase 2
Query!
Assessment method [34]
0
0
DCR was defined as the percentage of participants with a BOR of CR, PR or SD by Investigator assessment per RECIST v1.1. CR: disappearance of all target lesions. Any pathological lymph nodes must be \<10 mm on the short axis. PR: at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum of the diameters (e.g., percent change from baseline). SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to quality for PD. PD: at least a 20% increase in the sum of the diameters of target lesions, taking as a reference the smallest sum of diameters recorded since the treatment started (i.e., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of at least 5 mm.
Query!
Timepoint [34]
0
0
From date of first dose until disease progression, death due to any cause or subsequent therapy initiation, whichever occurred first in SLI Phase (approximately up to 10.4 months) and Phase 2 (approximately up to 8.3 months)
Query!
Secondary outcome [35]
0
0
Duration of Response (DOR) for Brain Metastasis Response Based on mRECIST v1.1: SLI Phase and Phase 2
Query!
Assessment method [35]
0
0
DOR: time from date of first radiographic response (CR or PR) to earliest documented disease progression or death due to any cause. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. DOR (months) = (date of event or censoring - date of first CR or PR + 1)/30.4375. If a participant with a CR or PR did not have an event at time of analysis cutoff or with an event more than 16 weeks (for first 11 cycles after treatment start date) or 24 weeks (after Cycle 11) after last adequate tumor assessment, participant was censored on date of last adequate tumor assessment that documented no progression.
Query!
Timepoint [35]
0
0
From date of first radiographic response (CR or PR) to earliest documented disease progression or death due to any cause in SLI Phase (approximately up to 10.4 months) and Phase 2 (approximately up to 8.3 months)
Query!
Secondary outcome [36]
0
0
DOR for Global Response: SLI Phase and Phase 2
Query!
Assessment method [36]
0
0
DOR: time from date of first radiographic response (CR or PR) to earliest documented disease progression or death due to any cause. CR: disappearance of all target lesions. Any pathological lymph nodes must be \<10 mm on the short axis. PR: at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum of the diameters (e.g., percent change from baseline). DOR (months) = (date of event or censoring - date of first CR or PR + 1)/30.4375. If a participant with a CR or PR did not have an event at time of analysis cutoff or with an event more than 16 weeks (for first 11 cycles after treatment start date) or 24 weeks (after Cycle 11) after last adequate tumor assessment, participant was censored on date of last adequate tumor assessment that documented no progression.
Query!
Timepoint [36]
0
0
From date of first radiographic response (CR or PR) to earliest documented disease progression or death due to any cause in SLI Phase (approximately up to 10.4 months) and Phase 2 (approximately up to 8.3 months)
Query!
Secondary outcome [37]
0
0
DOR for Extracranial Response Based on RECIST v1.1: SLI Phase and Phase 2
Query!
Assessment method [37]
0
0
DOR: time from date of first radiographic response (CR or PR) to earliest documented disease progression or death due to any cause. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. DOR (months) = (date of event or censoring - date of first CR or PR + 1)/30.4375. If a participant with a CR or PR did not have an event at time of analysis cutoff or with an event more than 16 weeks (for first 11 cycles after treatment start date) or 24 weeks (after Cycle 11) after last adequate tumor assessment, participant was censored on date of last adequate tumor assessment that documented no progression.
Query!
Timepoint [37]
0
0
From date of first radiographic response (CR or PR) to earliest documented disease progression or death due to any cause in SLI Phase (approximately up to 10.4 months) and Phase 2 (approximately up to 8.3 months)
Query!
Secondary outcome [38]
0
0
Progression Free Survival (PFS) for Brain Metastasis Based on mRECIST v1.1: SLI Phase and Phase 2
Query!
Assessment method [38]
0
0
PFS was defined as the time from date of the first dose of study treatment to the earliest documented disease progression (PD) by Investigator assessment, or death due to any cause, whichever occurs first. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase of at least 5 mm. If a participant did not had a PFS event at the time of the analysis cutoff or at the start of any new anticancer therapy, PFS was censored at the date of last adequate tumor assessment.
Query!
Timepoint [38]
0
0
From date of first dose of study treatment to the earliest documented disease progression by investigator assessment, or death due to any cause, whichever occurs first in SLI (approximately up to 10.4 months) and Phase 2 (approximately up to 8.3 months)
Query!
Secondary outcome [39]
0
0
PFS for Global Tumor Assessment: SLI Phase and Phase 2
Query!
Assessment method [39]
0
0
PFS was defined as the time from date of the first dose of study treatment to the earliest documented disease progression (PD) by Investigator assessment, or death due to any cause, whichever occurs first. PD: at least a 20% increase in the sum of the diameters of target lesions, taking as a reference the smallest sum of diameters recorded since the treatment started (i.e., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of at least 5 mm. Global tumor assessment consists of brain metastasis and extracranial lesions. If a participant did not had a PFS event at the time of the analysis cutoff or at the start of any new anticancer therapy, PFS was censored at the date of last adequate tumor assessment.
Query!
Timepoint [39]
0
0
From date of first dose of study treatment to the earliest documented disease progression by investigator assessment, or death due to any cause, whichever occurs first in SLI (approximately up to 10.4 months) and Phase 2 (approximately up to 8.3 months)
Query!
Secondary outcome [40]
0
0
BMRR Based on mRECIST v1.1: SLI Phase
Query!
Assessment method [40]
0
0
BMRR: percentage of participants who achieved a confirmed best overall response (BOR) of confirmed CR or PR in brain metastasis per mRECIST v1.1 from date of first dose until disease progression, death due to any cause, or start of subsequent anticancer therapy, whichever occurs first. BOR: best response recorded from date of first dose of study treatment until progression by investigator assessment at each time point. CR: Disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters (e.g., percent change from baseline).
Query!
Timepoint [40]
0
0
From date of first dose until disease progression, death due to any cause or subsequent therapy initiation, whichever occurred first in SLI Phase (approximately up to 10.4 months)
Query!
Secondary outcome [41]
0
0
Overall Survival: SLI Phase and Phase 2
Query!
Assessment method [41]
0
0
Overall survival (OS) was defined as the time from date of the first dose of study treatment to the date of death due to any cause. If a death was not observed by the date of the analysis cutoff, OS was censored at the date of last contact. OS (months) = (date of death or censoring - date of first dose +1)/30.4375
Query!
Timepoint [41]
0
0
From date of first dose of study treatment to the earliest documented disease progression by investigator assessment, or death due to any cause, whichever occurs first in SLI (approximately up to 10.4 months) and Phase 2 (approximately up to 8.3 months)
Query!
Secondary outcome [42]
0
0
Number of Participants With Treatment Emergent AEs of Maximum Severity Grades Based on NCI CTCAE v4.03: Phase 2
Query!
Assessment method [42]
0
0
AE was any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship.TEAEs were events between 1st dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state or start of subsequent anticancer drug therapy minus 1 day, whichever occurs first.Severity was graded by NCI CTCAE v.4.03.Grade 1:asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated;Grade 2:moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL;Grade 3:severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL;Grade 4:life-threatening consequence, urgent intervention indicated; Grade 5:death related to AE. Only those categories in which at least 1 participant had data were reported.
Query!
Timepoint [42]
0
0
Day 1 of dosing up to 30 days after last dose of study drug in Phase 2, maximum duration up to 8.3 months
Query!
Secondary outcome [43]
0
0
Number of Participants With Hepatology Laboratory Test Abnormalities: Phase 2
Query!
Assessment method [43]
0
0
Hepatology laboratory abnormalities included following parameters: ALT, AST, ALT or AST \>=3\*ULN, \>=5\*ULN, \>=10\*ULN, \>=20\*ULN; TBILI: \>=2\*ULN; ALT \>=3\*ULN and TBILI \>=2\*ULN; AST \>=3\*ULN and TBILI \>=2\*ULN; ALT or AST \>=3\*ULN and TBILI \>=2\*ULN; ALT or AST \>=3\*ULN and TBILI \>=2\*ULN and ALP \>2\*ULN; ALT or AST \>=3\*ULN and TBILI \>=2\*ULN and ALP \<=2\*ULN or missing. Only those laboratory test parameters in which at least 1 participant had data were reported.
Query!
Timepoint [43]
0
0
Baseline (Day 1) up to 30 days after last dose of study drug in Phase 2, maximum duration up to 8.3 months
Query!
Secondary outcome [44]
0
0
Number of Participants With Shift From Baseline for Hematology and Coagulation Laboratory Test Abnormalities Based on NCI-CTCAE v4.03: Phase 2
Query!
Assessment method [44]
0
0
Hematology and coagulation laboratory test included: activated partial thromboplastin time prolonged, anemia, hemoglobin increased, INR increased, leukocytosis, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased, and white blood cell decreased. Laboratory results were categorically summarized according to the NCI-CTCAE criteria v4.03. Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Grade 0 was assigned for all non-missing values not graded as 1 or higher per CTCAE criteria. Number of participants with shift from baseline for hematology and coagulation laboratory test were assessed. Only those laboratory test parameters in which at least 1 participant had data were reported.
Query!
Timepoint [44]
0
0
Baseline (Day 1) up to 30 days after last dose of study drug in Phase 2, maximum duration up to 8.3 months
Query!
Secondary outcome [45]
0
0
Number of Participants With Shift From Baseline for Biochemistry Laboratory Test Abnormalities Based on NCI-CTCAE v4.03: Phase 2
Query!
Assessment method [45]
0
0
Biochemistry laboratory test included: alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, CK increased, creatinine increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia, lipase increased, and serum amylase increased. Laboratory results were categorically summarized according to the NCI-CTCAE criteria v4.03. Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Grade 0 was assigned for all non-missing values not graded as 1 or higher per CTCAE criteria. Number of participants with shift from baseline for biochemistry laboratory test were assessed. Only those laboratory test parameters in which at least 1 participant had data were reported.
Query!
Timepoint [45]
0
0
Baseline (Day 1) up to 30 days after last dose of study drug in Phase 2, maximum duration up to 8.3 months
Query!
Secondary outcome [46]
0
0
Number of Participants With Clinically Significant Change in Notable Abnormal Vital Signs: Phase 2
Query!
Assessment method [46]
0
0
In this outcome measure, number of participants with notable abnormal vital signs included: systolic and diastolic BP in mmHg based on following criteria: 1) High Systolic BP: \>=160 mmHg and an increase \>=20 mmHg from baseline; 2) High Diastolic BP: \>=100 mmHg and an increase \>=15 mmHg from baseline; 3) Low Systolic BP: \<=90 mmHg with decrease from baseline of \>=20 mmHg; 4) Low Diastolic BP: \<=50 mmHg with decrease from baseline of \>=15 mmHg; pulse rate in bpm based on following criteria: 1) High pulse rate \>=120 bpm with increase from baseline of \>=15 bpm; 2) Low pulse rate \<=50 bpm with decrease from baseline of \>=15 bpm; weight in kg based on following criteria: 1) Weight: Increase from baseline of \>=10%, 2) Weight: \>=20 % decrease from baseline; temperature in degree C based on following criteria: 1) High body temperature \>=37.5 degree C, 2) Low body temperature \<=36 degree C. Only those vital signs parameters in which at least 1 participant had data were reported.
Query!
Timepoint [46]
0
0
Baseline (Day 1) up to 30 days after last dose of study drug in Phase 2, maximum duration up to 8.3 months
Query!
Secondary outcome [47]
0
0
Number of Participants With Notable Abnormal Electrocardiogram (ECG) Values: Phase 2
Query!
Assessment method [47]
0
0
In this outcome measure, number of participants with notable abnormal ECG values included: QTcF values in msec based on following criteria: 1) increase from baseline \>30 msec; 2) increase from baseline \>60 msec; 3) new \>450 msec; 4) new \>480 msec; and 5) new \>500 msec; heart rate values in bpm based on following criteria: 1) Increase from baseline \>25% and to a value \>100; 2) Decrease from baseline \>25% and to a value \<50. Only those vital ECG parameters in which at least 1 participant had data were reported.
Query!
Timepoint [47]
0
0
Baseline (Day 1) up to 30 days after last dose of study drug in Phase 2, maximum duration up to 8.3 months
Query!
Secondary outcome [48]
0
0
Plasma Concentrations of Encorafenib and Its Metabolite LHY746: SLI Phase
Query!
Assessment method [48]
0
0
In this outcome measure, plasma concentrations (in nanogram per milliliter \[ng/mL\]) of encorafenib and its metabolite LHY746 at Cycle 1 Day 1 (C1D1), Cycle 1 Day 15 (C1D15), Cycle 2 Day 1 (C2D1), and Cycle 3 Day 1 (C3D1) at different time points were reported.
Query!
Timepoint [48]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose; Pre-dose on Cycle 2 Day 1, Cycle 3 Day 1
Query!
Secondary outcome [49]
0
0
Plasma Concentrations of Binimetinib and Its Metabolite AR00426032: SLI Phase
Query!
Assessment method [49]
0
0
In this outcome measure, plasma concentrations of binimetinib and its metabolite AR00426032 at C1D1, C1D15, C2D1, and C3D1 at different time points were reported.
Query!
Timepoint [49]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose; Pre-dose on Cycle 2 Day 1, Cycle 3 Day 1
Query!
Secondary outcome [50]
0
0
Area Under the Plasma Concentration-Time Curve From Time Zero to 6 Hours (AUC 0-6) of Encorafenib and Its Metabolite LHY746: SLI Phase
Query!
Assessment method [50]
0
0
In this outcome measure, area under the plasma concentration-time curve from zero to 6 hours (AUC 0-6) after administration of encorafenib and its metabolite LHY746 in nanogram\*hour per milliliter (ng\*hr/mL) at C1D1, and C1D15 were assessed.
Query!
Timepoint [50]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Query!
Secondary outcome [51]
0
0
AUC0-6 of Binimetinib and Its Metabolite AR00426032: SLI Phase
Query!
Assessment method [51]
0
0
In this outcome measure, area under the plasma concentration-time curve from zero to 6 hours (AUC 0-6) after administration of binimetinib and its metabolite AR00426032 at C1D1, and C1D15 were assessed.
Query!
Timepoint [51]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Query!
Secondary outcome [52]
0
0
Area Under the Plasma Concentration-time Curve From Time Zero to Last Time Point (AUClast) of Encorafenib and Its Metabolite LHY746: SLI Phase
Query!
Assessment method [52]
0
0
In this outcome measure, area under the plasma concentration-time curve from zero to the last measurable time point (AUClast) after administration of encorafenib and its metabolite LHY746 at C1D1, and C1D15 were assessed.
Query!
Timepoint [52]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Query!
Secondary outcome [53]
0
0
AUClast of Binimetinib and Its Metabolite AR00426032: SLI Phase
Query!
Assessment method [53]
0
0
In this outcome measure, area under the plasma concentration-time curve from zero to the last measurable time point (AUClast) after administration of binimetinib and its metabolite AR00426032 at C1D1, and C1D15 were assessed.
Query!
Timepoint [53]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Query!
Secondary outcome [54]
0
0
Area Under the Plasma Concentration-time Curve From Time Zero to Tau (AUCtau) of Encorafenib and Its Metabolite LHY746: SLI Phase
Query!
Assessment method [54]
0
0
In this outcome measure, area under the plasma concentration-time curve from time zero to the last measurable time point Tau (AUCtau) of encorafenib and its metabolite LHY746 over a dosing interval (6 hours as appropriate) of C1D15 were assessed.
Query!
Timepoint [54]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Query!
Secondary outcome [55]
0
0
AUCtau of Binimetinib and Its Metabolite AR00426032: SLI Phase
Query!
Assessment method [55]
0
0
In this outcome measure, area under the plasma concentration-time curve from time zero to the last measurable time point Tau (AUCtau) of encorafenib and its metabolite LHY746 over a dosing interval (6 hours as appropriate) of C1D15 were assessed.
Query!
Timepoint [55]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Query!
Secondary outcome [56]
0
0
Maximum Observed Plasma Concentration (Cmax) After Drug Administration of Encorafenib and Its Metabolite LHY746: SLI Phase
Query!
Assessment method [56]
0
0
In this outcome measure, maximum observed plasma concentration (Cmax) after administration of encorafenib and its metabolite LHY746 at C1D1, and C1D15 were assessed.
Query!
Timepoint [56]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Query!
Secondary outcome [57]
0
0
Cmax of Binimetinib and Its Metabolite AR00426032: SLI Phase
Query!
Assessment method [57]
0
0
In this outcome measure, maximum observed plasma concentration (Cmax) after administration of binimetinib and its metabolite AR00426032 at C1D1, and C1D15 were assessed.
Query!
Timepoint [57]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Query!
Secondary outcome [58]
0
0
Minimum Observed Plasma Concentration (Cmin) at the End of a Dosing Interval at Steady State of Encorafenib and Its Metabolite LHY746: SLI Phase
Query!
Assessment method [58]
0
0
In this outcome measure, minimum observed plasma concentration (Cmin) after administration of encorafenib and its metabolite LHY746 at C1D15 were assessed.
Query!
Timepoint [58]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Query!
Secondary outcome [59]
0
0
Cmin of Binimetinib and Its Metabolite AR00426032: SLI Phase
Query!
Assessment method [59]
0
0
In this outcome measure, minimum observed plasma concentration (Cmin) after administration of binimetinib and its metabolite AR00426032 at C1D15 were assessed.
Query!
Timepoint [59]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Query!
Secondary outcome [60]
0
0
Ctrough of Encorafenib and Its Metabolite LHY746: SLI Phase
Query!
Assessment method [60]
0
0
In this outcome measure, measured concentration at the end of a dosing interval (Ctrough) of encorafenib and its metabolite LHY746 at C1D15 were assessed.
Query!
Timepoint [60]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose; Pre-dose on Cycle 2 Day 1, Cycle 3 Day 1
Query!
Secondary outcome [61]
0
0
Ctrough of Binimetinib and Its Metabolite AR00426032: SLI Phase
Query!
Assessment method [61]
0
0
In this outcome measure, measured concentration at the end of a dosing interval (Ctrough) of binimetinib and its metabolite AR00426032 at C1D15 were assessed.
Query!
Timepoint [61]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose; Pre-dose on Cycle 2 Day 1, Cycle 3 Day 1
Query!
Secondary outcome [62]
0
0
Time to Reach Maximum Concentration (Tmax) of Encorafenib and Its Metabolite LHY746: SLI Phase
Query!
Assessment method [62]
0
0
In this outcome measure, time to reach maximum concentration (Tmax) of encorafenib and its metabolite LHY746 at C1D1, and C1D15 were assessed.
Query!
Timepoint [62]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Query!
Secondary outcome [63]
0
0
Tmax of Binimetinib and Its Metabolite AR00426032: SLI Phase
Query!
Assessment method [63]
0
0
In this outcome measure, time to reach maximum concentration (Tmax) of binimetinib and its metabolite AR00426032 at C1D1, and C1D15 were assessed.
Query!
Timepoint [63]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hrs (+/- 20 minutes [min]) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs (+/- 20 min) post-dose
Query!
Secondary outcome [64]
0
0
Time of Last PK Sample (Tlast) of Encorafenib and Its Metabolite LHY746: SLI Phase
Query!
Assessment method [64]
0
0
In this outcome measure, time of last PK sample (Tlast) of encorafenib and its metabolite LHY746 at C1D1, and C1D15 were assessed. As outlined in the prespecified Statistical Analysis Plan for the study, since encorafenib was administered in continuous cycles, the pre-dose sample on Cycle 2 Day 1 was assumed to be at steady state and was interpolated as the concentration on 24 hours for encorafenib and LHY746 on Cycle 1 Day 15 during the analysis. In doing so, the reported Tlast values from the noncompartmental analysis (NCA) are 24 hours for encorafenib and LHY746.
Query!
Timepoint [64]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6, 24 hrs post-dose
Query!
Secondary outcome [65]
0
0
Tlast of Binimetinib and Its Metabolite AR00426032: SLI Phase
Query!
Assessment method [65]
0
0
In this outcome measure, time of last PK sample (Tlast) of binimetinib and its metabolite AR00426032 at C1D1, and C1D15 were assessed. As outlined in the prespecified Statistical Analysis Plan for the study, since binimetinib was administered in continuous cycles, the pre-dose sample on Cycle 2 Day 1 was assumed to be at steady state and was interpolated as the concentration for 12 hours for binimetinib and AR00426032 on Cycle 1 Day 15 for the noncompartmental analysis. In doing so, the reported Tlast values from the noncompartmental analysis (NCA) are 12 hours for binimetinib and AR00426032.
Query!
Timepoint [65]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6, 12 hrs post-dose
Query!
Secondary outcome [66]
0
0
Accumulation Ratio Between AUClast,ss and AUClast (RAUC) of Encorafenib and Its Metabolite LHY746: SLI Phase
Query!
Assessment method [66]
0
0
In this outcome measure, accumulation ratio of encorafenib and its metabolite LHY746 calculated as: C1D15 AUC0-6 divided by C1D1 AUC0-6 was assessed.
Query!
Timepoint [66]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Query!
Secondary outcome [67]
0
0
RAUC of Binimetinib and Its Metabolite AR00426032: SLI Phase
Query!
Assessment method [67]
0
0
In this outcome measure, accumulation ratio of binimetinib and its metabolite AR00426032 calculated as: C1D15 AUC0-6 divided by C1D1 AUC0-6 was assessed.
Query!
Timepoint [67]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Query!
Secondary outcome [68]
0
0
Accumulation Ratio Between Cmax,ss and Cmax (RCmax) of Encorafenib and Its Metabolite LHY746: SLI Phase
Query!
Assessment method [68]
0
0
In this outcome measure, accumulation ratio of encorafenib and its metabolite LHY746 calculated as: C1D15 Cmax divided by C1D1 Cmax was assessed.
Query!
Timepoint [68]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Query!
Secondary outcome [69]
0
0
Rcmax of Binimetinib and Its Metabolite AR00426032: SLI Phase
Query!
Assessment method [69]
0
0
In this outcome measure, accumulation ratio of binimetinib and its metabolite AR00426032 calculated as: C1D15 Cmax divided by C1D1 Cmax was assessed.
Query!
Timepoint [69]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Query!
Secondary outcome [70]
0
0
Ratio of AUClast Values of the Metabolite Compared to Parent (MRAUClast) of LHY746: SLI Phase
Query!
Assessment method [70]
0
0
In this outcome measure, ratio of AUClast values of the metabolite compared to parent, corrected for molecular weight, for LHY746/encorafenib at C1D1, and C1D15 was assessed.
Query!
Timepoint [70]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Query!
Secondary outcome [71]
0
0
MRAUClast of AR00426032: SLI Phase
Query!
Assessment method [71]
0
0
In this outcome measure, ratio of AUClast values of the metabolite compared to parent, corrected for molecular weight, for AR00426032/binimetinib at C1D1, and C1D15 was assessed.
Query!
Timepoint [71]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Query!
Secondary outcome [72]
0
0
Ratio of Cmax Values of the Metabolite Compared to Parent (MRCmax) of LHY746: SLI Phase
Query!
Assessment method [72]
0
0
In this outcome measure, ratio of Cmax values of the metabolite compared to parent, corrected for molecular weight, for LHY746/encorafenib at C1D1, and C1D15 was assessed.
Query!
Timepoint [72]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Query!
Secondary outcome [73]
0
0
MRCmax of AR00426032: SLI Phase
Query!
Assessment method [73]
0
0
In this outcome measure, ratio of Cmax values of the metabolite compared to parent, corrected for molecular weight, for AR00426032/ binimetinib at C1D1, and C1D15 was assessed.
Query!
Timepoint [73]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Query!
Eligibility
Key inclusion criteria
* Medically stable and appropriate for anticoagulant prophylaxis as determined by the investigator on the basis of physical examination, medical history, and vital signs performed as part of screening for elective total knee replacement (TKR) surgery
* Medically stable and appropriate for anticoagulant prophylaxis on the basis of clinical laboratory tests performed as part of local standard-of-care as part of screening for elective TKR surgery
* Has plans to undergo an elective primary unilateral TKR surgery
* A woman must be- a) Not of childbearing potential; b) Of childbearing potential and practicing a highly effective method of contraception (failure rate of less than [<]1 percent [%] per year when used consistently and correctly) and agrees to remain on a highly effective method for the duration of study drug with JNJ-70033093 plus 5 half-lives of study drug plus 30 days (duration of ovulatory cycle) for a total of 34 days after the completion of treatment, pregnancy testing (serum or urine) prior to the first dose of study drug
* Willing and able to adhere to the lifestyle restrictions specified in this protocol
Query!
Minimum age
50
Years
Query!
Query!
Maximum age
No limit
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
Key exclusion criteria
* History of any condition for which the use of low molecular-weight heparin (LMWH) is not recommended in the opinion of the investigator (for example, previous allergic reaction, creatinine clearance <30 milliliter per minute [mL/minute])
* History of severe hepatic impairment
* Planned bilateral revision or unicompartmental procedure
* Unable to undergo venography (for example, due to contrast agent allergy, poor venous access, or impaired renal function that would increase the risk of contrast-induced nephropathy
* Known previous pulmonary embolism (PE) or deep vein thrombosis (DVT) in either lower extremity
Query!
Study design
Purpose of the study
Prevention
Query!
Allocation to intervention
Randomised controlled trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Blinded (masking used)
Query!
Who is / are masked / blinded?
The people assessing the outcomes
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Phase 2
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Completed
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
17/06/2019
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
Query!
Actual
6/04/2021
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
1242
Query!
Recruitment in Australia
Recruitment state(s)
NSW
Query!
Recruitment hospital [1]
0
0
Crows Nest Eye Surgery - Crows Nest
Query!
Recruitment hospital [2]
0
0
Melanoma Institute Australia - North Sydney
Query!
Recruitment hospital [3]
0
0
Royal north shore center hospital dermatology clinics - st Leonards
Query!
Recruitment hospital [4]
0
0
Mater Imaging - Wollstonecraft
Query!
Recruitment postcode(s) [1]
0
0
2065 - Crows Nest
Query!
Recruitment postcode(s) [2]
0
0
2060 - North Sydney
Query!
Recruitment postcode(s) [3]
0
0
2065 - st Leonards
Query!
Recruitment postcode(s) [4]
0
0
2065 - Wollstonecraft
Query!
Recruitment outside Australia
Country [1]
0
0
Germany
Query!
State/province [1]
0
0
Berlin
Query!
Country [2]
0
0
United States of America
Query!
State/province [2]
0
0
Alabama
Query!
Country [3]
0
0
United States of America
Query!
State/province [3]
0
0
Arizona
Query!
Country [4]
0
0
United States of America
Query!
State/province [4]
0
0
Arkansas
Query!
Country [5]
0
0
United States of America
Query!
State/province [5]
0
0
California
Query!
Country [6]
0
0
United States of America
Query!
State/province [6]
0
0
Colorado
Query!
Country [7]
0
0
United States of America
Query!
State/province [7]
0
0
Florida
Query!
Country [8]
0
0
United States of America
Query!
State/province [8]
0
0
Texas
Query!
Country [9]
0
0
Argentina
Query!
State/province [9]
0
0
Caba
Query!
Country [10]
0
0
Argentina
Query!
State/province [10]
0
0
Ciudad Autonoma de Buenos Aires
Query!
Country [11]
0
0
Argentina
Query!
State/province [11]
0
0
Córdoba
Query!
Country [12]
0
0
Argentina
Query!
State/province [12]
0
0
La Plata
Query!
Country [13]
0
0
Argentina
Query!
State/province [13]
0
0
Rosario
Query!
Country [14]
0
0
Argentina
Query!
State/province [14]
0
0
San Martín
Query!
Country [15]
0
0
Belgium
Query!
State/province [15]
0
0
Antwerpen
Query!
Country [16]
0
0
Belgium
Query!
State/province [16]
0
0
Genk
Query!
Country [17]
0
0
Belgium
Query!
State/province [17]
0
0
Hasselt
Query!
Country [18]
0
0
Belgium
Query!
State/province [18]
0
0
Merksem
Query!
Country [19]
0
0
Brazil
Query!
State/province [19]
0
0
Belo Horizonte
Query!
Country [20]
0
0
Brazil
Query!
State/province [20]
0
0
Santo André
Query!
Country [21]
0
0
Bulgaria
Query!
State/province [21]
0
0
Pleven
Query!
Country [22]
0
0
Bulgaria
Query!
State/province [22]
0
0
Sofa
Query!
Country [23]
0
0
Bulgaria
Query!
State/province [23]
0
0
Sofia
Query!
Country [24]
0
0
Bulgaria
Query!
State/province [24]
0
0
Stara Zagora
Query!
Country [25]
0
0
Canada
Query!
State/province [25]
0
0
Ontario
Query!
Country [26]
0
0
Greece
Query!
State/province [26]
0
0
Kifisia
Query!
Country [27]
0
0
Greece
Query!
State/province [27]
0
0
Nea Ionia
Query!
Country [28]
0
0
Greece
Query!
State/province [28]
0
0
Patra
Query!
Country [29]
0
0
Greece
Query!
State/province [29]
0
0
Thessaloniki
Query!
Country [30]
0
0
Hungary
Query!
State/province [30]
0
0
Budapest
Query!
Country [31]
0
0
Hungary
Query!
State/province [31]
0
0
Debrecen
Query!
Country [32]
0
0
Hungary
Query!
State/province [32]
0
0
Gyõr
Query!
Country [33]
0
0
Hungary
Query!
State/province [33]
0
0
Kaposvar
Query!
Country [34]
0
0
Hungary
Query!
State/province [34]
0
0
Kecskemét
Query!
Country [35]
0
0
Hungary
Query!
State/province [35]
0
0
Szeged
Query!
Country [36]
0
0
Hungary
Query!
State/province [36]
0
0
Szekesfehervar
Query!
Country [37]
0
0
Hungary
Query!
State/province [37]
0
0
Szolnok
Query!
Country [38]
0
0
Israel
Query!
State/province [38]
0
0
Haifa
Query!
Country [39]
0
0
Israel
Query!
State/province [39]
0
0
Kfar Saba
Query!
Country [40]
0
0
Israel
Query!
State/province [40]
0
0
Rehovot
Query!
Country [41]
0
0
Italy
Query!
State/province [41]
0
0
Bergamo
Query!
Country [42]
0
0
Italy
Query!
State/province [42]
0
0
Bologna
Query!
Country [43]
0
0
Italy
Query!
State/province [43]
0
0
Pavia
Query!
Country [44]
0
0
Italy
Query!
State/province [44]
0
0
Rozzano
Query!
Country [45]
0
0
Italy
Query!
State/province [45]
0
0
Torino
Query!
Country [46]
0
0
Japan
Query!
State/province [46]
0
0
Chiba
Query!
Country [47]
0
0
Japan
Query!
State/province [47]
0
0
Hakodate
Query!
Country [48]
0
0
Japan
Query!
State/province [48]
0
0
Hamamatsu
Query!
Country [49]
0
0
Japan
Query!
State/province [49]
0
0
Itami-shi
Query!
Country [50]
0
0
Japan
Query!
State/province [50]
0
0
Kagoshima-shi
Query!
Country [51]
0
0
Japan
Query!
State/province [51]
0
0
Kitakyushu-shi,
Query!
Country [52]
0
0
Japan
Query!
State/province [52]
0
0
Matsumoto
Query!
Country [53]
0
0
Japan
Query!
State/province [53]
0
0
Nagoya
Query!
Country [54]
0
0
Japan
Query!
State/province [54]
0
0
Nerima-Ku
Query!
Country [55]
0
0
Japan
Query!
State/province [55]
0
0
Okayama
Query!
Country [56]
0
0
Japan
Query!
State/province [56]
0
0
Okinawa, Tomigusuku-shi
Query!
Country [57]
0
0
Japan
Query!
State/province [57]
0
0
Saitama-shi
Query!
Country [58]
0
0
Japan
Query!
State/province [58]
0
0
Saitama
Query!
Country [59]
0
0
Japan
Query!
State/province [59]
0
0
Suzaka
Query!
Country [60]
0
0
Japan
Query!
State/province [60]
0
0
Tokyo
Query!
Country [61]
0
0
Poland
Query!
State/province [61]
0
0
Bielsk Podlaski
Query!
Country [62]
0
0
Poland
Query!
State/province [62]
0
0
Grajewo
Query!
Country [63]
0
0
Poland
Query!
State/province [63]
0
0
Kielce
Query!
Country [64]
0
0
Poland
Query!
State/province [64]
0
0
Krakow
Query!
Country [65]
0
0
Poland
Query!
State/province [65]
0
0
Lodz
Query!
Country [66]
0
0
Poland
Query!
State/province [66]
0
0
Lublin
Query!
Country [67]
0
0
Poland
Query!
State/province [67]
0
0
Tarnow
Query!
Country [68]
0
0
Poland
Query!
State/province [68]
0
0
Warszawa
Query!
Country [69]
0
0
Poland
Query!
State/province [69]
0
0
Wroclaw
Query!
Country [70]
0
0
Portugal
Query!
State/province [70]
0
0
Aveiro
Query!
Country [71]
0
0
Portugal
Query!
State/province [71]
0
0
Cascais
Query!
Country [72]
0
0
Portugal
Query!
State/province [72]
0
0
Porto
Query!
Country [73]
0
0
Portugal
Query!
State/province [73]
0
0
Setubal
Query!
Country [74]
0
0
Portugal
Query!
State/province [74]
0
0
Viana do Castelo
Query!
Country [75]
0
0
Russian Federation
Query!
State/province [75]
0
0
Kurgan
Query!
Country [76]
0
0
Russian Federation
Query!
State/province [76]
0
0
Moscow
Query!
Country [77]
0
0
Russian Federation
Query!
State/province [77]
0
0
Nizhniy Novgorod
Query!
Country [78]
0
0
Russian Federation
Query!
State/province [78]
0
0
Saint-Petersburg
Query!
Country [79]
0
0
Russian Federation
Query!
State/province [79]
0
0
Samara
Query!
Country [80]
0
0
Russian Federation
Query!
State/province [80]
0
0
Smolensk
Query!
Country [81]
0
0
Russian Federation
Query!
State/province [81]
0
0
Sochi
Query!
Country [82]
0
0
South Africa
Query!
State/province [82]
0
0
Pretoria
Query!
Country [83]
0
0
South Africa
Query!
State/province [83]
0
0
Worcester
Query!
Country [84]
0
0
Spain
Query!
State/province [84]
0
0
Alcorcón
Query!
Country [85]
0
0
Spain
Query!
State/province [85]
0
0
Badalona
Query!
Country [86]
0
0
Spain
Query!
State/province [86]
0
0
Barcelona
Query!
Country [87]
0
0
Spain
Query!
State/province [87]
0
0
Jaen
Query!
Country [88]
0
0
Spain
Query!
State/province [88]
0
0
Madrid
Query!
Country [89]
0
0
Spain
Query!
State/province [89]
0
0
Sabadell
Query!
Country [90]
0
0
Spain
Query!
State/province [90]
0
0
Valencia
Query!
Country [91]
0
0
Turkey
Query!
State/province [91]
0
0
Adana
Query!
Country [92]
0
0
Turkey
Query!
State/province [92]
0
0
Ankara
Query!
Country [93]
0
0
Turkey
Query!
State/province [93]
0
0
Antalya
Query!
Country [94]
0
0
Turkey
Query!
State/province [94]
0
0
Istanbul
Query!
Country [95]
0
0
Turkey
Query!
State/province [95]
0
0
Izmir
Query!
Country [96]
0
0
Ukraine
Query!
State/province [96]
0
0
Ivano-Frankivsk
Query!
Country [97]
0
0
Ukraine
Query!
State/province [97]
0
0
Kharkiv
Query!
Country [98]
0
0
Ukraine
Query!
State/province [98]
0
0
Kyiv
Query!
Country [99]
0
0
Ukraine
Query!
State/province [99]
0
0
Lviv-Vynnyky
Query!
Country [100]
0
0
Ukraine
Query!
State/province [100]
0
0
Odesa
Query!
Country [101]
0
0
Ukraine
Query!
State/province [101]
0
0
Vinnytsia
Query!
Country [102]
0
0
Germany
Query!
State/province [102]
0
0
Bielefeld
Query!
Country [103]
0
0
Germany
Query!
State/province [103]
0
0
Bonn
Query!
Country [104]
0
0
Germany
Query!
State/province [104]
0
0
Frankfurt
Query!
Country [105]
0
0
Germany
Query!
State/province [105]
0
0
Hamburg
Query!
Country [106]
0
0
Germany
Query!
State/province [106]
0
0
Mahlow
Query!
Country [107]
0
0
Germany
Query!
State/province [107]
0
0
Schwerin
Query!
Country [108]
0
0
Hungary
Query!
State/province [108]
0
0
Kecskemet
Query!
Country [109]
0
0
Hungary
Query!
State/province [109]
0
0
Miskolc
Query!
Country [110]
0
0
Japan
Query!
State/province [110]
0
0
Hokkaido
Query!
Country [111]
0
0
Japan
Query!
State/province [111]
0
0
Osaka
Query!
Country [112]
0
0
Latvia
Query!
State/province [112]
0
0
Riga
Query!
Country [113]
0
0
Latvia
Query!
State/province [113]
0
0
Ventspils
Query!
Country [114]
0
0
Poland
Query!
State/province [114]
0
0
Bialystok
Query!
Country [115]
0
0
Poland
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State/province [115]
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Torun
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United States of America
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Oregon
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Argentina
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Ciudad Autónoma DE Buenosaires
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Argentina
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Santa FE
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Italy
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Naples
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Italy
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Napoli
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Michigan
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New York
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Canada
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Alberta
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Canada
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Quebec
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
Janssen Research & Development, LLC
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Address
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Other collaborator category [1]
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Commercial sector/industry
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Bristol-Myers Squibb
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Ethics approval
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Summary
Brief summary
The purpose of this study is to determine the efficacy of JNJ-70033093 in preventing total venous thromboembolism (VTE) events (proximal and/or distal deep vein thrombosis \[DVT\] \[asymptomatic confirmed by venography assessment or objectively confirmed symptomatic\], nonfatal pulmonary embolism \[PE\], or any death) during the treatment period.
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Trial website
https://clinicaltrials.gov/study/NCT03891524
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Trial related presentations / publications
Weitz JI, Strony J, Ageno W, Gailani D, Hylek EM, Lassen MR, Mahaffey KW, Notani RS, Roberts R, Segers A, Raskob GE; AXIOMATIC-TKR Investigators. Milvexian for the Prevention of Venous Thromboembolism. N Engl J Med. 2021 Dec 2;385(23):2161-2172. doi: 10.1056/NEJMoa2113194. Epub 2021 Nov 15.
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Public notes
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Contacts
Principal investigator
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Janssen Research & Development, LLC Clinical Trial
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Janssen Research & Development, LLC
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Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
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What data in particular will be shared?
The data sharing policy of the Janssen Pharmaceutical Companies of Johnson \& Johnson is available at www.janssen.com/clinicaltrials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
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When will data be available (start and end dates)?
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Available to whom?
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Available for what types of analyses?
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How or where can data be obtained?
IPD available at link: https://www.janssen.com/clinical-trials/transparency
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What supporting documents are/will be available?
No Supporting Document Provided
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Other Details
Attachment
Study protocol
https://cdn.clinicaltrials.gov/large-docs/24/NCT03891524/Prot_002.pdf
Statistical analysis plan
https://cdn.clinicaltrials.gov/large-docs/24/NCT03891524/SAP_003.pdf
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results are available at
https://clinicaltrials.gov/study/NCT03891524