A Phase 1 Open-Label Study to Evaluate the Metabolism and Excretion of CC-223 and the Effect of Food on the Pharmacokinetics of CC-223 in Healthy Male Adult Subjects
Condition: Safety and Pharmacokinetics in Healthy Volunteer Subjects
Study type: Interventional
Phase: Phase 1

Summary: 
      Part 1: To characterize the biotransformation and excretion of CC-223 following a single
      20-mg oral dose of CC-223 capsule containing a microtracer of [14C]-CC-223 solution in
      healthy male subjects; and to evaluate the tolerability of CC-223 after a single 20-mg oral
      dose of CC-223 capsule containing a microtracer of [14C]-CC-223 solution in healthy male
      adult subjects Part 2: To evaluate the effect of a high-fat meal on the pharmacokinetics (PK)
      of CC-223 following a single 20-mg oral dose of CC-223 tablet; To evaluate the effect of a
      high-fat meal on the PK of M1, the principal pharmacologically-active metabolite, following a
      single 20-mg oral dose of CC-223 tablet; and to evaluate the tolerability of CC-223 after a
      single 20-mg oral dose of CC-223 tablet in healthy male adult subjects.
    

Detailed description: 
      This will be a single-center, 2-part, open-label, randomized (Part 1 only), 2-treatment study
      in healthy adult males (n = 18). Within no more than 28 days (Day -28) prior to the start of
      Part 1 or Part 2, subjects will undergo routine screening procedures including physical
      examination, 12-lead electrocardiograms (ECGs), vital signs, clinical laboratory safety tests
      (serum chemistry, hematology, and urinalysis), serology screen, fasting glucose levels
      (including HbA1C) and drug and alcohol screen.

      In Part 1, subjects (n = 6) will receive Treatment A (Cohort 1) under fasted conditions.
      Treatment A: A single 20-mg oral dose of CC-223 capsule containing a microtracer of [14C]-
      CC-223 solution. For Part 1, subjects will be domiciled at the study center from Day -1 until
      the morning of Day 8. Upon satisfactory safety review and completion of study-related
      procedures, subjects will be discharged from the study center on the morning of Day 8.

      Part 2 will be a 2-period crossover study; in Period 1, subjects (n = 12) will be randomized
      to receive an oral 20 mg dose of CC-223 (Treatment B) under fed (n = 6) or fasted (n = 6)
      conditions. In Period 2, subjects will receive Treatment B under converse conditions based on
      treatment assignment in Period 1 (Cohort 2 or 3). Fed subjects will be served a standard high
      fat meal (breakfast), or its equivalent, and must be consumed within 30 minutes of serving.
      Dosing must occur 30 minutes (±5 minutes) after serving a subject breakfast. All subjects
      will remain fasted until 4 hours post dose. Subjects will be domiciled at the study center
      from Day -1 until the morning of Day 5 of each period. Subjects will be discharged from the
      study center on the morning of Day 5 upon satisfactory safety review and completion of
      study-related procedures. Periods 1 and 2 will be separated by a washout period of at least 7
      days (no more than 10 days) from prior dose to the next dose. In certain instances, a longer
      washout may be acceptable if previously agreed to by the principal investigator (PI) and
      Celgene.

      All subjects will return to the clinic within 7 to 10 days after the day of discharge in Part
      1 or Period 2 of Part 2 for follow-up safety assessments.
    

Intervention name(s): CC-223; CC-223
Intervention type(s): Drug; Drug
Intervention description(s): 20 mg oral CC-223 capsule containing a microtracer of [14C]-CC-223 solution; 20-mg oral CC-223 tablet under fasting or fed conditions
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: CC-223; safety; tolerability; pharmacokinetic; AME (Absorption, Metabolism, and Excretion); FE (Food Effect)