This is a single-center, randomized, double-blind crossover study with four treatments, four periods and four sequences to investigate the effects of orally administered pomalidomide on QT interval. The study will be conducted in healthy male subjects. Pomalidomide (clinically indicated dose for multiple myeloma \[MM\] as per the United States Package Insert \[USPI\] of 4 mg and supratherapeutic dose of 20 mg) and placebo treatments will be double-blinded. Moxifloxacin (positive control) will be administered in an open-label fashion to determine the sensitivity of the assay. The core electrocardiogram (ECG) laboratory and ECG readers will be blinded to all study treatments and sequences.
A total of 72 male subjects will be randomized and enrolled, with 18 subjects assigned to each treatment sequence. For each treatment sequence, each subject will participate in a screening phase, four baseline phases, four treatment periods and a follow up visit. Within 28 days prior to Period 1 dosing, subjects will sign an informed consent document (ICD) and undergo screening procedures to confirm eligibility. Qualifying subjects will return to the clinical site on Day -2 of Period 1 to begin baseline assessments, and will be domiciled at the clinical site from Day -2 to Day 2 of Period 1. For all remaining study periods, subjects will return to the clinical site on Day -1 to begin baseline assessments, and will be domiciled at the clinical site from Day -1 to Day 2. Subjects will be assigned randomly to one of four treatment sequences and will receive a single dose of the assigned treatment on Day 1 of each study period. There will be a minimum of 7 days and no more than 14 days between each dose. Subjects will begin an overnight fast of at least 8 hours prior to the start of continuous Holter monitoring on Day 1 (and Day 1 in Period 1). On the morning of Day 1 (and Day -1 in Period 1), continuous Holter monitoring for approximately 24 hours will be performed. Triplicate ECGs will be extracted for analysis at specific predose and postdose timepoints (or equivalent times on Day -1 of Period 1). Blood samples will be collected at pre specified timepoints for pharmacokinetic (PK) and clinical laboratory assessments. Safety will be monitored throughout the study. During each study period, subjects will be discharged from the clinical site on Day 2 upon satisfactory safety review and completion of the required study procedures. A safety follow up will be conducted by telephone 5 to 7 days following discharge in Period 4. In the event that a subject discontinues from the study, an early termination visit will be performed.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
QUADRUPLE
Enrollment
72
Single oral dose of Placebo
Single oral dose of 4 mg pomalidomide
Single oral dose of 20 mg pomalidomide
Single oral dose of 400 mg moxifloxacin tablet
PPD Phase I Clinic
Austin, Texas, United States
Time matched, baseline corrected change from placebo of QTcF
To evaluate the effect of pomalidomide on the time matched changes from placebo in the baseline adjusted QT interval of the electrocardiogram (ECG) using the Fridericia correction method (QTcF)
Time frame: From before dosing until 23 hours after dosing
Categorical analyses on ECG intervals and changes in ECG morphology
Time frame: From before dosing until 23 hours after dosing
Time matched, baseline corrected changes from placebo of other ECG intervals (RR, PR, QRS) and categorical analyses on ECG intervals and changes in ECG morphology
To evaluate the change from placebo in selected ECG parameters (heart rate, PR interval, QRS interval, uncorrected QT interval and morphological patterns) following pomalidomide treatment
Time frame: From before dosing until 23 hours after dosing
Safety
To assess the safety and tolerability of single oral doses of pomalidomide
Time frame: 2 months (from screening visit until end of study
Pharmacokinetics - Cmax
Maximum observed plasma concentration
Time frame: From before dosing until 32 hours after dosing
Pharmacokinetics - Tmax
Time to Cmax
Time frame: From before dosing until 32 hours after dosing
Pharmacokinetics - AUCinf
Area under the plasma concentration time curve from time zero extrapolated to infinity
Time frame: From before dosing until 32 hours after dosing
Pharmacokinetics - AUCt
Area under the plasma concentration time curve from time zero to the last quantifiable concentration
Time frame: From before dosing until 32 hours after dosing
Pharmacokinetics - t1/2
Terminal phase elimination half-life
Time frame: From before dosing until 32 hours after dosing
Pharmacokinetics - CL/F
Apparent total plasma clearance when dosed orally
Time frame: From before dosing until 32 hours after dosing
Pharmacokinetics - Vz/F
Apparent total volume of distribution when dosed orally, based on the terminal phase
Time frame: From before dosing until 32 hours after dosing
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