PK and Safety Study of AG-221 in Healthy Male Japanese Subjects and Healthy Male Caucasian Subjects
Condition: Healthy
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a single ascending dose, open-label study that will evaluate the pharmacokinetics and
      safety of the AG-221 compound in normal, healthy volunteer male subjects (both Japanese and
      Caucasian).
    

Detailed description: 
      This is a phase 1, single ascending dose study to evaluate the PK and safety of AG-221 in
      healthy adult male Japanese subjects relative to healthy adult male Caucasian subjects. A
      total of 60 subjects will be enrolled; 30 will be Japanese subjects and 30 will be Caucasian
      subjects. There will be a total of 3 cohorts. Cohort A will receive a single dose of 100 mg
      AG-221. Cohort B will receive a single dose of 50 mg AG-221. Cohort C will receive a single
      dose of 300 mg AG-221. Within each cohort, 10 subjects will be Japanese and 10 subjects will
      be Caucasian.

      Investigational product (IP) will be administered orally with approximately 240 mL of
      noncarbonated, room-temperature water. Subjects will enter the clinic prior to the evening
      meal on the day before dosing (Day -1) and will take a single oral dose of AG-221 at Hour 0
      on the dosing day (Day 1), following a 10 hour overnight fast. After the dose is
      administered, subjects will be observed for 7 days to assess the acute safety profile before
      the next higher, protocol specified dose cohorts can enroll. The Sponsor and Investigator
      will review all available safety information prior to escalation to the next cohort to ensure
      that no safety issues exist.

      Subjects will be confined to the study center from Day -1 to Day 3. Subjects will be
      discharged from the study center upon completion of the 48 hour PK blood draw. Subjects will
      return to the study center for additional PK blood draws on Days 5, 8, 11, 15, 22 and 29. In
      the event that a subject discontinues from the study, an early termination visit will be
      performed.

      Blood samples will be collected at the following time (hours) for analysis of AG-221 and
      AGI-16903 (minor, active metabolite in humans) concentrations: Pre-dose, 1, 2, 3, 4, 6, 9,
      12, 18, 24, 48, 96, 168, 240, 336, 504 and 672 hours.

      In accordance with the guidance for clinical pharmacokinetic studies in Japan, this study
      design was selected to obtain PK data from Japanese in comparison to Caucasian healthy
      subjects. As the IP is an anticancer agent and, following the Japanese guidance for global
      studies, a single dose design was chosen.

      AG-221 is a novel, first-in-class compound targeted specifically to inhibit the mutated IDH2
      enzyme. AG-221 is currently being studied in a Phase 1 dose escalation study in subjects with
      advanced hematologic malignancies harboring an IDH2 mutation (AG221-C-001). The AG221-C-001
      study is currently being conducted in the United States and France. This Japanese PK bridging
      study is intended to provide single dose PK and safety information in healthy Japanese
      subjects, relative to healthy Caucasian
    

Intervention name(s): AG-221
Intervention type(s): Drug
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: Pharmacokinetic; Healthy Volunteers; Male; Japanese; Caucasian; AG-221