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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT02431364
Registration number
NCT02431364
Ethics application status
Date submitted
22/04/2015
Date registered
1/05/2015
Date last updated
20/01/2023
Titles & IDs
Public title
Trial of Safety and Tolerability of Oral Verdinexor (KPT-335) in Healthy Adults
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Scientific title
A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Sequential, Dose-Escalating Trial to Evaluate the Safety and Tolerability of Oral Verdinexor (KPT-335) in Healthy Adult Subjects
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Secondary ID [1]
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KCP-335-701
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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:
Healthy
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Condition category
Condition code
Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Verdinexor
Other interventions - Placebo
Placebo Comparator: Placebo - Participants received matched placebo tablets to verdinexor tablets orally once daily on Days 1 and 3.
Experimental: Verdinexor 5 mg - Participants received verdinexor 5 milligrams (mg) (2 tablets of 2.5 mg each) orally once daily on Days 1 and 3.
Experimental: Verdinexor 10 mg - Participants received verdinexor 10 mg tablet orally once daily on Days 1 and 3.
Experimental: Verdinexor 20 mg - Participants received verdinexor 20 mg tablet (2 tablets of 10 mg each) orally once daily on Days 1 and 3.
Experimental: Verdinexor 40 mg - Participants received verdinexor 40 mg tablet (4 tablets of 10 mg each) orally once daily on Days 1 and 3.
Treatment: Drugs: Verdinexor
Participants received verdinexor; Dosage form: coated, immediate release Tablet; Route of administration: oral
Other interventions: Placebo
Participants received placebo matched to verdinexor; Dosage form: coated, immediate release Tablet; Route of administration: oral
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Intervention code [1]
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Treatment: Drugs
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Intervention code [2]
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Other interventions
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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 Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
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Assessment method [1]
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An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign, symptom, or medical condition that occur after participant's signed informed consent obtained. A serious adverse event (SAE) was defined as any AE, occurring at any dose (including after the informed consent form was signed and prior to dosing) that and regardless of causality that: results in death, was life-threatening (participant was at immediate risk of death from event as it occurred), requires in-patient hospitalization (formal admission to a hospital for medical reasons) or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect. TEAE was defined as any AE with onset or worsening of a pre-existing condition on or after the first administration of study treatment through 30 days following last dose or any event considered drug-related by the investigator through the end of the study.
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Timepoint [1]
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From start of study drug administration up to Day 33
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Secondary outcome [1]
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Area Under the Concentration-time Curve From Time Zero to the Last Non-zero Concentration (AUC0-t) of Verdinexor
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Assessment method [1]
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AUC0-t was defined as area under the concentration-time curve from time zero to the last non-zero concentration
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Timepoint [1]
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Days 1 and 3: pre-dose, 15 minutes, 30 minutes, 1, 2, 3, 4, 8, 12, 24, 48 (only for Day 3) hours post-dose
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Secondary outcome [2]
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Area Under the Concentration-time Curve From Time Zero to Extrapolated to Infinity (AUC0-inf) of Verdinexor
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Assessment method [2]
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AUC0-inf was defined as area under the concentration-time curve from time zero to infinity (extrapolated). It was calculated as AUC0-t + Ct/kel, where: Ct = the last observed non-zero concentration, kel = elimination rate constant.
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Timepoint [2]
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Days 1 and 3: pre-dose, 15 minutes, 30 minutes, 1, 2, 3, 4, 8, 12, 24, 48 (only for Day 3) hours post-dose
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Secondary outcome [3]
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Maximum Observed Concentration (Cmax) of Verdinexor
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Assessment method [3]
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Cmax was defined as maximum observed concentration, taken directly from the plasma concentration data.
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Timepoint [3]
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Days 1 and 3: pre-dose, 15 minutes, 30 minutes, 1, 2, 3, 4, 8, 12, 24, 48 (only for Day 3) hours post-dose
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Secondary outcome [4]
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Average Plasma Concentration From Time Zero to 24 Hours Post-dose (Cavg0-24h) of Verdinexor
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Assessment method [4]
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Cavg0-24h was defined as average plasma concentration from time zero to 24 hours post-dose.
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Timepoint [4]
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Days 1 and 3: pre-dose, 15 minutes, 30 minutes, 1, 2, 3, 4, 8, 12, 24 hours post-dose
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Secondary outcome [5]
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Time of First Observation of Maximum Observed Concentration (Tmax) of Verdinexor
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Assessment method [5]
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Tmax was defined as time of first observation of Cmax, taken directly from the plasma concentration data.
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Timepoint [5]
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Days 1 and 3: pre-dose, 15 minutes, 30 minutes, 1, 2, 3, 4, 8, 12, 24, 48 (only for Day 3) hours post-dose
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Secondary outcome [6]
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Elimination Rate Constant (Kel) of Verdinexor
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Assessment method [6]
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Elimination rate constant was calculated using linear regression on the terminal portion of the log-linear concentration versus time curve.
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Timepoint [6]
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Days 1 and 3: pre-dose, 15 minutes, 30 minutes, 1, 2, 3, 4, 8, 12, 24, 48 (only for Day 3) hours post-dose
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Secondary outcome [7]
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Elimination Half-life (t1/2) of Verdinexor
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Assessment method [7]
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t1/2 was defined as elimination half-life, it was calculated as ln(2)/kel.
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Timepoint [7]
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Days 1 and 3: pre-dose, 15 minutes, 30 minutes, 1, 2, 3, 4, 8, 12, 24, 48 (only for Day 3) hours post-dose
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Secondary outcome [8]
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Apparent Total Body Clearance (Cl/F) of Verdinexor
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Assessment method [8]
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Apparent total body clearance was calculated as Dose/AUC0-inf, uncorrected for fraction absorbed; reported normalized by participant body weight (kilogram [kg]).
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Timepoint [8]
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Days 1 and 3: pre-dose, 15 minutes, 30 minutes, 1, 2, 3, 4, 8, 12, 24, 48 (only for Day 3) hours post-dose
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Secondary outcome [9]
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Apparent Volume of Distribution (Vd/F) of Verdinexor
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Assessment method [9]
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Vd/F was calculated as Dose/ (kel *AUC0-inf), uncorrected for fraction absorbed; reported normalized by participant body weight (kg).
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Timepoint [9]
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Days 1 and 3: pre-dose, 15 minutes, 30 minutes, 1, 2, 3, 4, 8, 12, 24, 48 (only for Day 3) hours post-dose
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Secondary outcome [10]
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Accumulation Factor (AR) of Cmax
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Assessment method [10]
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An AR was defined as a ratio of mean of Cmax Day 3/ Cmax Day 1 for plasma verdinexor.
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Timepoint [10]
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Days 1 and 3: pre-dose, 15 minutes, 30 minutes, 1, 2, 3, 4, 8, 12, 24, 48 (only for Day 3) hours post-dose
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Secondary outcome [11]
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Accumulation Factor (AR) of Cavg0-24Hour
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Assessment method [11]
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An AR was defined as a ratio of mean of Cavg0-24hour Day 3/ Cavg0-24hour Day 1 for plasma verdinexor.
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Timepoint [11]
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Days 1 and 3: pre-dose, 15 minutes, 30 minutes, 1, 2, 3, 4, 8, 12, 24 hours post-dose
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Secondary outcome [12]
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Accumulation Factor (AR) of AUC0-t
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Assessment method [12]
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An AR factor was defined as a ratio of mean of AUC0-t Day 3/ AUC0-t Day 1 for plasma verdinexor.
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Timepoint [12]
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Days 1 and 3: pre-dose, 15 minutes, 30 minutes, 1, 2, 3, 4, 8, 12, 24, 48 (only for Day 3) hours post-dose
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Secondary outcome [13]
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Accumulation Factor (AR) of AUC0-inf
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Assessment method [13]
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Accumulation factor was defined as a ratio of mean of AUC0-inf Day 3/ AUC0-inf Day 1 for plasma verdinexor.
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Timepoint [13]
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Days 1 and 3: pre-dose, 15 minutes, 30 minutes, 1, 2, 3, 4, 8, 12, 24, 48 (only for Day 3) hours post-dose
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Secondary outcome [14]
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Maximum Tolerated Dose (MTD) of Verdinexor
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Assessment method [14]
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MTD was defined as the dose level tested in the cohort immediately preceding a cohort where one or more dose limiting toxicities (DLTs) were observed. A DLT was defined as any AE or abnormal laboratory value that the Investigator suspected was probably related to verdinexor that was severe in intensity or serious or Indicative of an unacceptable risk to additional participants in the study in the opinion of the Investigator or Sponsor.
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Timepoint [14]
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From start of study drug administration up to Day 8
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Eligibility
Key inclusion criteria
- Participants must be in good health as determined by the investigator, based on the
medical history, ECG, physical examination, and safety laboratory tests at screening.
- Participants must be identified as a non-smoker at the screening visit (a non-smoker
is defined as an individual who has abstained from smoking for at least 1 year prior
to the screening visit and who has a = 15 pack year history of lifetime cigarette
use). A urine cotinine test will be performed at screening and at the time of clinic
check-in prior to study drug treatment.
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Minimum age
18
Years
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Maximum age
45
Years
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Sex
Both males and females
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Can healthy volunteers participate?
Yes
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Key exclusion criteria
- The participant has any surgical or medical condition that potentially may alter the
absorption, metabolism, or excretion of the study drug such as gastrectomy, Crohn's
disease, or liver disease.
- The participant has a history of clinically significant allergies. Hay fever is
allowed unless it is active or has required treatment within the previous 2 months.
- Presence of a chronic condition(s) with clinical or historical evidence of recent
exacerbation, or other information to suggest non-control of such condition(s).
- History of alcohol abuse or drug addiction within 12 months of the screening visit.
- Any participant with active cataracts or medical history of cataracts.
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Study design
Purpose of the study
Basic Science
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Allocation to intervention
Randomised controlled 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
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people analysing the results/data
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Intervention assignment
Other
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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
Terminated
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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
26/05/2015
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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
1/10/2015
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Sample size
Target
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Accrual to date
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Final
33
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Recruitment in Australia
Recruitment state(s)
VIC
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Recruitment hospital [1]
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Nucleus Network - Melbourne
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Recruitment postcode(s) [1]
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- Melbourne
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Karyopharm Therapeutics Inc
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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
This is a randomized, double-blind, sequential, dose-escalation, Phase 1 trial to evaluate
the safety and tolerability of verdinexor. Verdinexor or placebo will be given on Days 1 and
3 to healthy adult participants.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT02431364
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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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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 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
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT02431364
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