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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT01236352
Registration number
NCT01236352
Ethics application status
Date submitted
5/11/2010
Date registered
7/11/2010
Date last updated
31/07/2019
Titles & IDs
Public title
Multiple Ascending Dose of BMS-911543
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Scientific title
A Phase 1/2 Multiple Ascending Dose Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of BMS-911543 in Subjects With Myelofibrosis
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Secondary ID [1]
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CA215-001
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Cancer
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Condition category
Condition code
Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Experimental: Phase 1 (Cohort 1): BMS-911543 (5 mg) - BMS-911543 5 mg capsule by mouth twice daily for 12 months or greater depending on response
Experimental: Phase 1 (Cohort 2): BMS-911543 (10 mg) - BMS-911543 10 mg capsule by mouth twice daily for 12 months or greater depending on response
Experimental: Phase 1 (Cohort 3): BMS-911543 (20 mg) - BMS-911543 20 mg capsule by mouth twice daily for 12 months or greater depending on response
Experimental: Phase 1 (Cohort 4): BMS-911543 (40 mg) - BMS-911543 40 mg capsule by mouth twice daily for 12 months or greater depending on response
Experimental: Phase 1 (Cohort 5): BMS-911543 (80 mg) - BMS-911543 80 mg capsule by mouth twice daily for 12 months or greater depending on response
Experimental: Phase 1 (Cohort 6): BMS-911543 (120 mg) - BMS-911543 120 mg capsule by mouth twice daily for 12 months or greater depending on response
Experimental: Phase 1 (Cohort 7): BMS-911543 (160 mg) - BMS-911543 160 mg capsule by mouth twice daily for 12 months or greater depending on response
Experimental: Phase 1 (Cohort 8): BMS-911543 (200 mg) - BMS-911543 200 mg capsule by mouth twice daily for 12 months or greater depending on response
Experimental: Phase 1 (Cohort 9): BMS-911543 (240 mg) - BMS-911543 240 mg capsule by mouth twice daily for 12 months or greater depending on response
Experimental: Phase 1 (Cohort 10): BMS-911543 (320 mg) - BMS-911543 320 mg capsule by mouth twice daily for 12 months or greater depending on response
Experimental: Phase 2 (Cohort 11): BMS-911543 (120 mg) - BMS-911543 120 mg capsule by mouth twice daily for 12 months or greater depending on response
Experimental: Phase 2 (Cohort 12): BMS-911543 (200 mg) - BMS-911543 200 mg capsule by mouth twice daily for 12 months or greater depending on response
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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 Adverse Events
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Assessment method [1]
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Safety assessments were based on a medical review of adverse event reports and the results of vital sign measurements, ECGs, physical examinations, and clinical laboratory tests and were evaluated for all treated participants using National Cancer Institute Common Terminology Criteria for Adverse Events v4.0 (NCI CTCAE v.4.0).
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Timepoint [1]
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From the date of participant's written consent until 30 days post discontinuation of dosing or participation in the study if the last scheduled visit occured at a later time, assessed up to 4.5 years
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Primary outcome [2]
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Number of Participants With Best Overall Response
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Assessment method [2]
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Participants were clinically assessed for IWG-(International Working Group consensus criteria for treatment response in myelofibrosis with myeloid metaplasia) defined response at each returning on-treatment visit and the first post-treatment visit. IWG-MRT criteria for best overall response are ordered high to low: CR\>PR\>CI\>SD\>PD\>R where CR = Complete Remission, PR= Partial Remission, CI = Clinical Improvement, SD = Stable Disease, PD = Progressive Disease and R = Relapse. Best overall response is the best response of the subject during the treatment period or at the first post-treatment visit.
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Timepoint [2]
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Day 1, at each returning on-treatment visit and the first post-treatment visit
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Secondary outcome [1]
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Changes in (Janus Kinase) JAK/Signal Transducers and Activators of Transcription (STATs) Pathway Activities, Circulating CD34+ Cells and Plasma Cytokine Levels
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Assessment method [1]
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JAK/STAT pathway activity will be evaluated by: 1) pSTATs levels using immunoassay; 2) expression levels of several JAK/STATs pathway genes. Whole blood will be collected at specific time-points. Due to portfolio/business decisions by the sponsor, the compound is no longer being developed and the study was terminated. Analysis was not completed because the study was terminated. This decision was not based on any safety concerns associated with BMS-911543.
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Timepoint [1]
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Up to 6 months
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Secondary outcome [2]
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Maximum Observed Plasma Concentration (Cmax) of BMS-911543 and it's Metabolite BMS-926796 (Met4)
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Assessment method [2]
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Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time. The pharmacokinetic parameters to be assessed include: Cmax Maximum observed plasma concentration
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Timepoint [2]
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Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
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Secondary outcome [3]
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Trough Observed (Pre-dose) Plasma Concentration (Cmin) of BMS-911543 and it's Metabolite Met4
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Assessment method [3]
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Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time. The pharmacokinetic parameters to be assessed include: Cmin (Trough observed (pre-dose) plasma concentration)
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Timepoint [3]
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Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
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Secondary outcome [4]
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Time of Maximum Observed Plasma Concentration (Tmax) of BMS-911543 and it's Metabolite Met4
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Assessment method [4]
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Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time. The pharmacokinetic parameters to be assessed include: Tmax = Time of maximum observed plasma concentration (Tmax) of BMS-911543 and it's metabolite Met4
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Timepoint [4]
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Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
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Secondary outcome [5]
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Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time (for Single Dose Period Only) (AUC(INF)) of BMS-911543 and it's Metabolite Met4
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Assessment method [5]
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Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time. The pharmacokinetic parameters to be assessed include: AUC(INF) = Area under the plasma concentration-time curve from time zero extrapolated to infinite time (for single dose period only) (AUC(INF)) of BMS-911543 and it's metabolite Met4
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Timepoint [5]
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Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
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Secondary outcome [6]
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Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Plasma Concentration (for Single Dose Period Only) (AUC(0-T)) of BMS-911543 and it's Metabolite Met4
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Assessment method [6]
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Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time. The pharmacokinetic parameters to be assessed include: AUC (0-T) = Area under the plasma concentration-time curve from time zero to the time of last quantifiable plasma concentration (for single dose period only) of BMS-911543 and it's metabolite Met4
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Timepoint [6]
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Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
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Secondary outcome [7]
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Area Under the Concentration-time Curve in One Dosing Interval (AUC(TAU)) of BMS-911543 and it's Metabolite Met4
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Assessment method [7]
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Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time. The pharmacokinetic parameters to be assessed include: AUC (TAU) = Area under the concentration-time curve in one dosing interval of BMS-911543 and it's metabolite Met4
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Timepoint [7]
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Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
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Secondary outcome [8]
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The Terminal-phase Elimination Half-life in Plasma (T-HALF) of BMS-911543 and it's Metabolite Met4
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Assessment method [8]
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Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time. The pharmacokinetic parameters to be assessed include: T-HALF = The terminal-phase elimination half-life in plasma of BMS-911543 and it's metabolite Met4
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Timepoint [8]
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Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
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Secondary outcome [9]
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Apparent Total Clearance (for Parent Compound Only) (CLT/F) of BMS-911543 and it's Metabolite Met4
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Assessment method [9]
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Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time. The pharmacokinetic parameters to be assessed include: CLT/F = Apparent total clearance (for parent compound only) of BMS-911543 and it's metabolite Met4
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Timepoint [9]
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Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
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Secondary outcome [10]
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Apparent Volume of Distribution After First Dosing Based on the Terminal Phase (for Parent Compound Only) (Vz/F) of BMS-911543 and it's Metabolite Met4
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Assessment method [10]
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Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time. The pharmacokinetic parameters to be assessed include: Vz/F = Apparent volume of distribution after first dosing based on the terminal phase (for parent compound only) of BMS-911543 and it's metabolite Met4
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Timepoint [10]
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Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
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Secondary outcome [11]
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Accumulation Index (AI): Ratio of AUC(TAU) on Day 15 to AUC(TAU) After the First Dose of BMS-911543 and it's Metabolite Met4
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Assessment method [11]
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Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time. The pharmacokinetic parameters to be assessed include: Accumulation index (AI) = ratio of AUC(TAU) on Day 15 to AUC(TAU) after the first dose of BMS-911543 and it's metabolite Met4
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Timepoint [11]
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Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
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Secondary outcome [12]
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Ratio of BMS-926796 AUC(INF) to BMS-911543 AUC(INF) After 1st Dose and BMS-926796 AUC(TAU) to BMS-911543 AUC(TAU) on Day 15 (AUC Ratio)
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Assessment method [12]
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Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time. The pharmacokinetic parameters to be assessed include: AUC Ratio = Ratio of BMS-926796 AUC(INF) to BMS-911543 AUC(INF) after 1st dose and BMS-926796 AUC(TAU) to BMS-911543 AUC(TAU) on Day 15
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Timepoint [12]
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Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
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Eligibility
Key inclusion criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.
* Men and Women at least 18 years old
* A diagnosis of symptomatic, primary or secondary Myelofibrosis (MF) [World Health Organization (WHO) 2008 criteria] with intermediate-1, intermediate-2 or high risk disease as assessed using the Dynamic International Prognostic Scoring System international prognostic scoring system
* Last therapeutic or diagnostic treatment at least 28 days prior
* Any toxicity from prior therapies must have resolved to Grade =1
* Adequate Liver and Kidney Function
* Serum amylase and lipase within normal institutional range
* Platelet count =50,000 cell mm³
* Absolute neutrophil count (ANC) =1,000 cells/mm3
* Hemoglobin =8.0 g/dL
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Minimum age
No limit
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
* Primary central nervous system tumors
* Subjects with currently active malignancy (other than MF) or with a prior history of malignancy with the exception of: (i) adequately treated basal cell carcinoma of the skin, (ii) curatively treated in situ carcinoma of the cervix, (iii) other malignancy that has undergone potentially curative therapy with no evidence of disease recurrence =3 years
* Any condition requiring chronic use of moderate/high dose steroids except inhalation or oral steroids for mild pulmonary disease
* Splenic irradiation =3 months prior to treatment with study drug
* Positive blood screen for hepatitis C antibody, hepatitis B surface antigen or Human Immunodeficiency Virus-1 (HIV-1), or HIV-2 antibodies
* Abnormalities in serum electrolytes
* Significant cardiovascular disease
* Current or recent gastrointestinal disease
* Previous history of pancreatitis and/or significant risk factors for pancreatitis as judged by the treating physician
* Evidence of uncontrolled active infection or active graft vs. host disease
* Inability to tolerate oral medication
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Non-randomised trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 1
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Stopped early
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
7/04/2011
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
19/11/2015
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Sample size
Target
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Accrual to date
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Final
98
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Recruitment in Australia
Recruitment state(s)
VIC
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Recruitment hospital [1]
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Local Institution - East Melbourne
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Recruitment hospital [2]
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Local Institution - Melbourne
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Recruitment postcode(s) [1]
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3002 - East Melbourne
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Recruitment postcode(s) [2]
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3050 - Melbourne
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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Minnesota
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Country [2]
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United States of America
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State/province [2]
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New York
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Country [3]
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United States of America
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State/province [3]
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Texas
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
Bristol-Myers Squibb
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Address
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Country
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Ethics approval
Ethics application status
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Summary
Brief summary
The purpose of this first in human study is to determine if BMS-911543 is safe and tolerable in subjects with symptomatic intermediate-1, intermediate-2 or high risk myelofibrosis to permit clinical testing at the Maximum Tolerated Dose or at a Clinically Active Dose, and to determine if BMS-911543 will demonstrate efficacy in symptomatic myelofibrosis.
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Trial website
https://clinicaltrials.gov/study/NCT01236352
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Bristol-Myers Squibb
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Address
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Bristol-Myers Squibb
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Country
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Phone
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Fax
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Email
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Contact person for scientific queries
No information has been provided regarding IPD availability
What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results are available at
https://clinicaltrials.gov/study/NCT01236352
Download to PDF