A Study to Evaluate AG-881 in Healthy Japanese and Non-Asian Participants

1. Have provided voluntary written informed consent.

2. Adult male or female, 18 to 55 years of age, inclusive, at Screening.

3. Continuous nonsmoker who has not used nicotine containing products for at least 3 months prior to the first dosing and throughout the study.

4. Have a body mass index (BMI) of ≥ 18.0 and ≤ 32.0 kg/m^2 at Screening.

5. Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs, or ECG. Liver function tests (serum alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP], and bilirubin [total and direct]) must be ≤ the upper limit of normal (ULN).

6. Female participants must be of nonchildbearing potential defined as a female who has undergone one of the following sterilization procedures at least 6 months prior to the first dosing: hysteroscopic sterilization; bilateral tubal ligation or bilateral salpingectomy; hysterectomy; bilateral oophorectomy. Or is postmenopausal with amenorrhea for at least 1 year prior to the first dosing and follicle-stimulating hormone (FSH) serum levels consistent with postmenopausal status.

7. A nonvasectomized, male participant must agree to use a condom with spermicide or abstain from sexual intercourse during the study until 90 days after the last dosing. (No restrictions are required for a vasectomized male provided his vasectomy has been performed 4 months or more prior to the first dosing of study drug. A male who has been vasectomized less than 4 months prior to study first dosing must follow the same restrictions as a nonvasectomized male).

8. Male participants must agree not to donate sperm from the first dosing until 90 days after the last dosing.

9. Understands the study procedures in the informed consent form (ICF), and be willing and able to comply with the protocol.

10. Additional Criteria for Japanese participants only: be first-generation Japanese, defined as meeting all of the following conditions: born in Japan; has 2 Japanese biological parents and 4 Japanese biological grandparents; has lived outside of Japan for <5 years; has made no significant changes in lifestyle, including diet, since leaving Japan.

11. Additional Criteria for Non-Asian participants only: Non-Asian participants will have 2 biological parents and 4 biological grandparents of Non-Asian descent.

1. Mentally or legally incapacitated or has significant emotional problems at the time of the Screening visit or expected during the conduct of the study.

2. History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the Investigator or designee.

3. History of any illness that, in the opinion of the Investigator or designee, might confound the results of the study or pose an additional risk to the participant (eg, history or presence of rashes) by their participation in the study.

4. History of stomach or intestinal surgery that would potentially alter absorption/secretion; or any major surgical procedure within the previous 3 months prior to Screening.

5. History of severe and/or uncontrolled ventricular arrhythmias, or other factors that increase the risk of QT prolongation or arrhythmic events (eg, heart failure, hypokalemia, family history of long QT interval syndrome).

6. History or presence of alcoholism or drug abuse within the past 2 years prior to the first dosing.

7. History or presence of hypersensitivity or idiosyncratic reaction to the study drugs or related compounds.

8. Any positive responses on the Columbia-Suicide Severity Rating Scale (C-SSRS).

9. Female participants of childbearing potential.

10. Female participants with a positive pregnancy test or who are lactating.

11. Positive urine drug or alcohol results at Screening or Day -1/Day 21.

12. Positive results at Screening for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HbsAg), or hepatitis C virus (HCV) antibodies.

13. QTcF interval is >450 msec, or QRS interval >110 msec, or PR interval >220 msec, or participants who have ECG findings deemed abnormal with clinical significance by the Investigator or designee at Screening.

14. Supine blood pressure is less than 90/40 mmHg or greater than 140/90 mmHg at Screening.

15. Supine heart rate is lower than 40 beats per minute (bpm) or higher than 99 bpm at Screening.

16. Estimated creatinine clearance <90 mL/min at Screening.

17. Unable to refrain from or anticipates the use of: any drug, including prescription and non-prescription medications, herbal remedies, and vitamin supplements, beginning 14 days prior to the first dosing and throughout the study. After first dosing, acetaminophen (<2 g per 24 hour) may be administered at the discretion of Investigator or designee. Hormone replacement therapy will not be allowed; any drugs known to be strong inducers of CYP3A, CYP2C9, or CYP2C19 enzymes including St. John's Wort and/or, gastric acid reducing agents (eg, protonpump inhibitors, H2-receptor antagonists, antacids) for 28 days, or drugs that can prolong the QT interval for 28 days, prior to the first dosing and throughout the study. Appropriate sources (eg, Flockhart TableTM) will be consulted to confirm lack of PK/Pharmacodynamic (PD) interaction with study drug.

18. Refuses to abstain from alcohol from 48 hours prior to the first dosing and throughout the study.

19. Refuses to abstain from grapefruit-containing foods or beverages or Seville orange containing foods or beverages from 14 days prior to the first dosing and throughout the study.

20. Donation of blood or significant blood loss within 56 days prior to the first dose.

21. Plasma donation within 7 days prior to the first dose.

22. Receipt of blood or blood products within 2 months prior to the first dose.

23. Participation in another clinical study within 30 days prior to the first dose. The 30-day window will be derived from the date of the last blood collection or dosing, whichever is later, in the previous study to Day 1 of Period 1 of the current study.