A Study to Determine How Tebapivat is Absorbed, Broken Down, and Removed From the Body and the Extent to Which Tebapivat is Made Available in the Body in Healthy Participants

Agios Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Healthy Participants

Treatments: Drug: [13C2,15N3]-tebapivat; Drug: [14C]-tebapivat

Study type: Interventional

Funder types: Industry

Identifiers

NCT06745271

AG946-C-004

Details and patient eligibility

About

The primary purpose of this study is to determine the routes, rates of elimination, mass balance of total radioactivity and metabolite profiles following a single oral dose of [14C]-tebapivat. To characterize the PK of tebapivat and [13C2,15N3]-tebapivat and determine the absolute bioavailability following single oral dose of [14C]-tebapivat relative to single intravenous microdose of [13C2,15N3]-tebapivat to healthy male participants.

Enrollment: 8 patients

Sex: Male

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Male, of any race, between 18 and 55 years of age, inclusive.

   a. Males must agree to use contraception.

2. Body mass index between 18.0 and 30.0 kilograms per meter square (kg/m2), inclusive, and a body weight between 50 and 100 kilograms (kg), inclusive.

3. In good health, as determined by no clinically significant findings from medical history, 12-lead ECG and vital signs measurements, and clinical laboratory evaluations (congenital nonhemolytic hyperbilirubinemia [e.g., suspicion of Gilbert's syndrome based on total and direct bilirubin] is not acceptable) at screening and check-in, and from the physical examination at check-in, as assessed by the investigator or designee.

4. History of a minimum of 1 bowel movement per day.

5. Able to comprehend and are willing to sign the informed consent form (ICF) and abide by the study restrictions.

Exclusion criteria

1. 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.
2. History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, as determined by the investigator or designee.
3. 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 are allowed; cholecystectomy is not allowed).
4. Positive hepatitis panel and/or positive human immunodeficiency virus test. Participants whose results are compatible with prior immunization may be included.
5. Administration of any vaccine within 30 days prior to dosing.
6. Use or intend to use any medications/products known to alter drug absorption, metabolism, and excretion (AME) processes, including St. John's wort, within 30 days prior to dosing, considered to potentially impact participant safety or the objectives of the study, as determined by the investigator or designee.
7. Use or intend to use any prescription medications/products within 14 days or 5 half-lives (whichever is longer) prior to dosing, considered to potentially impact participant safety or the objectives of the study, as determined by the investigator or designee.
8. Use or intend to use any slow release medications/products considered to still be active within 14 days or 5 half-lives (whichever is longer) prior to dosing, considered to potentially impact participant safety or the objectives of the study, as determined by the investigator or designee.
9. Use or intend to use any nonprescription medications/products including vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations within 7 days prior to dosing, considered to potentially impact participant safety or the objectives of the study, as determined by the investigator or designee.
10. Participation in a clinical study involving administration of an IMP (new chemical entity) in the past 30 days or 5 half-lives of that drug (if known) prior to dosing, whichever is longer.
11. Have previously completed or withdrawn from this study or any other study investigating tebapivat and have previously received tebapivat.
12. Participants who have previously been dosed in >1 radiolabeled drug study in the last 12 months. For participants who have previously been dosed in 1 radiolabeled drug study within the last 12 months, the previous radiolabeled dose must be at least 6 months prior to check-in at the clinical research unit (CRU). The total 12 month exposure from this study and a maximum of 1 other previous radiolabeled study must be within the Code of Federal Regulations (CFR) recommended levels considered safe, per United States (US) Title 21 CFR 361.1.
13. Alcohol consumption of >21 units per week. One unit of alcohol equals 12 ounces (oz) (360 milliliters (mL)) beer, 1½ oz (45 mL) liquor, or 5 oz (150 mL) wine.
14. Positive urine drug screen at screening or positive alcohol test result or positive urine drug screen at check-in.
15. History of alcoholism or drug/chemical abuse within 2 years prior to check-in.
16. Use of tobacco- or nicotine-containing products within 3 months prior to check-in, or positive cotinine at screening or check-in.
17. Receipt of blood products within 2 months prior to check-in.
18. Donation of blood from 3 months prior to screening, plasma from 2 weeks prior to screening, or platelets from 6 weeks prior to screening.
19. Poor peripheral venous access.
20. 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.
21. Participants who, in the opinion of the investigator or designee, should not participate in this study.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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8 participants in 1 patient group

[14C]-tebapivat and [13C2,15N3]-tebapivat

Experimental group

Description:

Participants will receive a single oral dose of 10 milligrams (mg) \[14C\]-tebapivat containing 200 microcurie \[μCi\] of radiocarbon in a capsule followed by a single intravenous (IV) microdose of 0.1 mg \[13C2,15N3\]-tebapivat on Day 1.

Treatment:

Drug: [14C]-tebapivat

Drug: [13C2,15N3]-tebapivat