The purpose of this Phase I, open-label study is to evaluate the absorption, distribution, metabolism, excretion, absolute bioavailability, and to characterize the metabolites of AG-881 in healthy male participants following administration of a single oral dose of [14C] AG-881 and a concomitant intravenous microdose of [13C315N3] AG-881.

Inclusion Criteria:

• Able to comprehend and willing to sign an informed consent form (ICF) and to abide by the study restrictions, including confinement, as well as adhere to all study procedures;
• Males of any race, between 18 and 55 years of age, inclusive;
• Body mass index between 18.0 and 32.0 kilograms per meter squared (kg/m^2), inclusive, and a total body weight between 50 and 100 kg, inclusive;
• In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead electrocardiogram (ECG), vital sign measurements, and clinical laboratory evaluations (congenital non-hemolytic hyperbilirubinemia [e.g., suspicion of Gilbert's syndrome based on total and direct bilirubin] is not acceptable) at Screening and/or Check-in (Day -1), as assessed by the Investigator (or designee);
• Alanine aminotransferase (ALT; at or within normal limits [WNL]), aspartate aminotransferase (AST; at or within normal limits), alkaline phosphatase (ALP; <1.5 × upper limit of normal [ULN]), bilirubin (at or below WNL). One repeat assessment allowed at each time point;
• Male participants will agree to use contraception;
• Agrees to abstain from any alcohol consumption, starting 48 hours before Check-in (Day -1) and continuing until Discharge;
• History of a minimum of one bowel movement per day;
• Adequate peripheral venous access.

Exclusion Criteria:

• Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the Investigator (or designee);
• History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee);
• History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy and hernia repair will be allowed);
• Has undergone any major surgical procedure within the 3 months prior to Screening;
• History of alcoholism or drug/chemical abuse within 2 years prior to Check-in (Day -1);
• History of severe and/or uncontrolled ventricular arrhythmias or other factors that increase the risk of long QT syndrome, or use, or intend to use, medications that are known to prolong the QT interval or history of unexplained syncopal events or familial history of unexplained death in young person;
• After at least 5 minutes of rest in the supine position at Screening, has a systolic blood pressure reading of ≥140 millimeters of mercury (mmHg) OR a diastolic blood pressure reading of ≥90 mmHg;
• A heart rate-corrected QT interval by Fridericia's (QTcF) method of ≥450 milliseconds (ms);
• Alcohol consumption of >21 units per week. One unit of alcohol equals 12 ounces (360 millimeters [mL]) of beer, 1½ oz (45 mL) of liquor, or 5 oz (150 mL) of wine;
• Positive urine drug screen at Screening or positive alcohol breath test result or positive urine drug screen at Check-in (Day -1);
• Positive hepatitis panel and/or positive human immunodeficiency virus test;
• Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 30 days or 5 half-lives (whichever is longer), prior to dosing;
• Use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John's wort, within 30 days prior to Check-in (Day -1), unless deemed acceptable by the Investigator (or designee);
• Use or intend to use any prescription medications/products within 14 days prior to Check-in (Day -1), unless deemed acceptable by the Investigator (or designee);
• Use or intend to use slow-release medications/products considered to still be active within 30 days prior to Check-in (Day -1), unless deemed acceptable by the Investigator (or designee);
• Use or intend to use any nonprescription medications/products including vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations within 7 days prior to Check-in (Day -1), unless deemed acceptable by the Investigator (or designee);
• Use of tobacco- or nicotine-containing products within 3 months prior to Check-in (Day -1), or positive cotinine at Screening or Check-in (Day -1);
• Receipt of blood products within 2 months prior to Check-in (Day -1);
• Donation of blood from 3 months prior to Screening, plasma from 2 weeks prior to Screening, or platelets from 6 weeks prior to Screening;
• Have previously completed or withdrawn from this study or any other study investigating AG-881, and have previously received the investigational product;
• Participants with exposure to significant diagnostic or therapeutic radiation (e.g., serial X-ray, computed tomography scan, barium meal) or current employment in a job requiring radiation exposure monitoring within 12 months prior to Check-in (Day -1);
• Participants who have participated in a radiolabeled drug study where exposures are known to the Investigator within the previous 4 months prior to admission to the clinic for this study or participated in a radiolabeled drug study where exposures are not known to the Investigator within the previous 6 months prior to admission to the clinic for this study. The total 12-month exposure from this study and a maximum of 2 other previous radiolabeled studies within 4 to 12 months prior to this study will be within the Code of Federal Regulations (CFR) recommended levels considered safe, per United States (US) Title 21 CFR 361.1: less than 5,000 millirems (mrem) whole-body annual exposure with consideration given to the half-lives of the previous radiolabeled study drugs received;
• Is an employee of, or an immediate family member of an employee of, the study site or the Sponsor;
• Participants who, in the opinion of the Investigator (or designee), should not be part of this study.