Radiolabeled Study of AG-221 in Healthy Male Subjects.
Condition: Healthy Volunteers
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a single-center, 2-part, open-label study to evaluate the metabolism and excretion
      and absolute bioavailability of [14C]-AG-221 in healthy male subjects. It is planned for 14
      subjects to be enrolled; each subject will participate in a screening phase, a baseline
      phase, a treatment phase, and a follow up phone call. Blood, urine and fecal samples will be
      collected in Part 1 for analyses. Blood samples will be collected in Part 2. Subjects can
      only participate in either Part 1 or Part 2.
    

Detailed description: 
      This will be a single-center, open-label, 2-part study in healthy adult males (n = 14). Parts
      1 and 2 may be conducted in parallel.

      Each subject will participate in a screening phase, a baseline phase, a treatment phase, and
      a follow up phone call. Subjects who have met all inclusion criteria and none of the
      exclusion criteria at screening will return to the clinical site on Day 1 for baseline
      assessments.

      Part 1: Absorption, metabolism, and excretion (AME) Approximately 8 subjects will be enrolled
      in Part 1. Subjects will check into the clinic on the day before dosing. Following a 10 hour
      overnight fast, subjects will receive a single 100-mg dose of AG-221 solution containing a
      microtracer of [14C] AG 221 (~ 300 nCi) under fasted conditions. The study drug will be
      administered as an oral solution with approximately 240 mL of room temperature,
      non-carbonated water.

      Blood, urine, and fecal samples (and vomitus, if applicable) will be collected throughout the
      study for pharmacokinetic (PK), mass balance, and/or clinical laboratory assessments. Safety
      will be monitored throughout the study. Subjects will be discharged from the clinical site on
      Day 22 following completion of the required study procedures. Subjects will return to the
      unit on Day 29 for the last PK blood draw.

      Urine and fecal samples will be collected each day until Day 22 (or the point of discharge if
      earlier) for measurement of total [14C] radioactivity. Blood samples for radioanalysis and PK
      assessment, inclusive of metabolite profiling/characterization, will be collected at pre-dose
      and at specified intervals through Day 29. Total [14C]-radioactivity in whole blood, plasma,
      urine, and feces (and vomitus, if applicable ) will be determined.

      Part 2: Absolute bioavailability:

      Approximately 6 subjects will be enrolled in Part 2. Qualified subjects who have met all
      inclusion criteria and none of the exclusion criteria at screening will return to the
      clinical site on Day 1, and will be housed at the clinical site from Day 1 until Day 3.

      After an overnight fast of at least 10 hours, approximately 6 subjects will receive an oral
      dose (coated tablet) of 100 mg of AG-221 at Hour 0 on dosing day (Day 1). The study drug will
      be administered orally with approximately 240 mL of water. Four hours after the oral dose,
      the subjects will receive 100 micrograms AG-221 containing ~300 nCi of
      [14C]-AG-221administered as an intravenous bolus over approximately 2 minutes.

      Subjects will be discharged from the unit upon completion of the 48 hour PK blood draw on Day
      3. Subjects will return to the unit for additional PK blood draws on Days 5, 8, 11, 15, 18,
      22, and 29.

      No urine and fecal samples will be collected in Part 2.
    

Intervention name(s): AG-221; 14C AG-221
Intervention type(s): Drug; Radiation
Intervention description(s): Part 1: oral solution containing 100 mg [14C]-AG-221; 5 mL of 100 micrograms [14C] AG-221 given intravenously 4 hours after swallowing the formulated tablet.
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: Pharmacokinetic; Healthy; Male; AG-221; [14C]; Single dose; Oral; Intravenous