The main purpose of this study is to examine the effect of multiple doses of AG-881 on the pharmacokinetics (PK) of a single dose of lamotrigine in healthy adults.

Inclusion criteria

• Healthy, adult, male or female participants, 18-55 years of age, inclusive, at screening;

• Continuous non-smoker who has not used nicotine-containing products for at least 3 months prior to the first dosing and throughout the study, based on participant self-reporting;

• Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kilograms per square meter (kg/m^2) at screening;

• Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or electrocardiograms (ECG), as deemed by the principal investigator or designee;

• 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;

• Female participants must be of non-childbearing 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;

• A non-vasectomized, 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 non-vasectomized male);

• If a male participant, must agree not to donate sperm from the first dosing until 90 days after the last dosing;

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

Exclusion criteria:

• Participant is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study;

• History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the principal investigator or designee;

• History of any illness that, in the opinion of the principal investigator or designee, might confound the results of the study or pose an additional risk to the participant (e.g., history or presence of rashes) by their participation in the study;

• History or presence of ventricular dysfunction or risk factors for Torsades de Pointes (e.g., heart failure, hypokalemia, cardiomyopathy, family history of Long QT Syndrome), in the opinion of the principal investigator or designee;

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

• History or presence of hypersensitivity or idiosyncratic reaction to the study drugs or related compounds;

• Known medical history of progressive multifocal leukoencephalopathy;

• Presence of an active skin rash;

• Any positive responses on the Columbia-suicide severity rating scale (C-SSRS);

• Female participants of childbearing potential;

• Female participants with a positive pregnancy test or who are lactating;

• Positive urine drug or alcohol results at screening or first check-in;

• Positive results at screening for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies;

• Corrected QT interval by Fridericia (QTcF) is >450 milliseconds (msec), or Q wave, R wave, and S wave complex (QRS) interval >110 msec, or P wave to the start of the QRS complex (PR interval) >220 msec or participants who have ECG findings deemed abnormal with clinical significance by the principal investigator or designee at screening;

• Estimated creatinine clearance <90 millimeters per minute (mL/min) at screening;

• Unable to refrain from or anticipate 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, ibuprofen (1.2 grams [g] per 24 hours) may be administered at the discretion of principal investigator or designee;
  • Any drugs known to be strong inducers of cytochrome P450 (CYP) 3A enzymes or uridine 5´-diphospho-glucuronyl transferases (UGTs), including St. John's Wort, for 28 days prior to the first dosing and throughout the study. Appropriate sources (e.g., Flockhart Table™) will be consulted to confirm lack of pharmacokinetic/pharmacodynamic interaction with study drug;

• 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;

• Has been on a diet incompatible with the on-study diet, in the opinion of the principal investigator or designee, within the 30 days prior to the first dosing and throughout the study;

• Donation of blood or significant blood loss within 56 days prior to the first dose;

• Plasma donation within 7 days prior to the first dose;

• 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 the current study.