A Phase 1 Open-Label Study to Evaluate the Effect of CYP450 and P-gp Inhibition and Induction on the Pharmacokinetics of Pomalidomide (CC-4047) in Healthy Male Subjects
Condition: Pharmacology, Clinical; Healthy
Study type: Interventional
Phase: Phase 1

Summary: 
      1. To evaluate the pharmacokinetics (PK) of pomalidomide administered with the CYP3A4/P-gp
           inhibitor ketoconazole compared with pomalidomide alone in healthy male subjects.

        2. To evaluate the PK of pomalidomide administered with the CYP3A4/P-gp inhibitor
           ketoconazole plus the CYP1A2 inhibitor fluvoxamine compared with pomalidomide alone in
           healthy male subjects.

        3. To assess the PK of pomalidomide administered with the CYP1A2 inhibitor fluvoxamine and
           the CYP3A4/P-gp inhibitor ketoconazole compared with pomalidomide plus the CYP3A4/P-gp
           inhibitor ketoconazole in healthy male subjects.

      Part 2

      1) To evaluate the pharmacokinetics of pomalidomide administered with the CYP3A4 inducer
      carbamazepine compared with pomalidomide alone in healthy male volunteers.

      Secondary Objectives

      1) To evaluate the safety of pomalidomide in Part 1 and Part 2 when administered with
      ketoconazole, fluvoxamine and/or carbamazepine.

      In addition: To evaluate the safety of pomalidomide in Part 1 and Part 2 when administered
      with ketoconazole, fluvoxamine and/or carbamazepine.
    

Detailed description: 
      This will be a single-center, open label non randomized, 2-part study with 3 periods in Part
      1, and 2 periods in Part 2. Parts 1 and 2 will be conducted in parallel. The entire study
      will consist of a screening phase, two dosing parts, and a follow-up telephone call for
      safety. All Periods will be separated by a washout period of at least 3 days (no more than 5
      days) from the last pomalidomide dose to the next drug dose.

      Safety will be monitored throughout the study. Safety evaluations will include adverse event
      (AE) reporting, concomitant medications, PEs, vital sign measurements, 12-lead ECGs, and
      clinical laboratory safety tests.

      Thirty-two healthy (16 per each Part), male adult subjects 18 to 55 years of age who meet all
      inclusion criteria and do not meet any of the exclusion criteria will be enrolled in the
      study. Subjects enrolled in Part 1 cannot participate in Part 2 and vice versa.

      Study treatments (pomalidomide, ketoconazole, fluvoxamine and carbamazepine) should be
      administered with meals and subjects should be a served a standard meal (ie, breakfast or
      dinner) approximately 30 minutes prior to dosing. The meal should be consumed within 30
      minutes from serving and dosing must occur 30 minutes (±5 minutes) after serving the meal.
      Subjects should be encouraged to consume the whole meal served prior to dosing. After each
      dosing, food and beverages (except water) will be withheld from all subjects until at least 4
      hours post dose; thereafter, subjects will be served standard meals and snacks.

      For determination of plasma concentrations of pomalidomide, ketoconazole, fluvoxamine and
      carbamazepine (and its active metabolite carbamazepine 10,11-epoxide) in each dosing regimen
      (Period), serial blood samples will be collected.

      A safety follow-up will be conducted by telephone within 4 to 7 days from the last dose. In
      the event a subject discontinues from the study prematurely, an early termination visit will
      be performed within 4 days following the day of discontinuation.
    

Intervention name(s): Pomalidomide; Ketoconazole; Fluvoxamine; Carbamazepine
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): 4 mg pomalidomide capsule administered orally once in the morning; 200 mg Ketoconazole tablet administered orally twice a day on Days 1-7.; 50 mg Fluvoxamine tablet administered orally twice a day on Days 1-7.; 100 mg Carbamazepine tablet administered orally once in the evening on Day 1
100 mg Carbamazepine tablet administered orally twice daily on Days 2-3
200 mg Carbamazepine tablet administered orally twice daily on Days 4-11
Other intervention name(s): (CC-4047)
Intervention MeSH terms: Ketoconazole; Pomalidomide; Carbamazepine; Fluvoxamine
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: CC-4047; Pomalidomide; Ketoconazole; Fluvoxamine; Carbamazepine; DDI; safety; tolerability; pharmacokinetic