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

Phase 1

Completed

• Conditions: Healthy Participants
• Interventions: Drug: [14C]-tebapivat; Drug: [13C2,15N3]-tebapivat

• Registration Number: NCT06745271
• Lead Sponsor: Agios Pharmaceuticals, Inc.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-12-17
• Study First Submitted QC: 2024-12-17
• Study Start: 2024-12-20
• Study First Posted: 2024-12-20
• Primary Completion: 2025-02-21
• Study Completion: 2025-02-21
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-17
• Last Update Posted: 2025-03-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 8

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
[14C]-tebapivat and [13C2,15N3]-tebapivat	[14C]-tebapivat	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.
[14C]-tebapivat and [13C2,15N3]-tebapivat	[13C2,15N3]-tebapivat	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.

Primary Outcome Measures

Name	Time	Method
Ratio of AUC0-inf for Total Radioactivity in Whole Blood to AUC0-inf for Total Radioactivity in Plasma	Up to Day 42
Total Clearance Following IV Administration (CL) of [13C2,15N3]-Tebapivat	Up to Day 21
Apparent Volume of Distribution During the Terminal Phase Following IV Administration (Vz) of [13C2,15N3]-Tebapivat	Up to Day 21
Apparent Volume of Distribution at Steady State Following IV Administration (Vss) of [13C2,15N3]-Tebapivat	Up to Day 21
T1/2 in Plasma and Whole Blood for Total Radioactivity	Up to Day 42
Ratio of AUC0-inf for Tebapivat to AUC0-inf for Total Radioactivity in Plasma	Up to Day 42
Terminal Elimination Half-Life (t1/2) in Plasma for [14C]-Tebapivat and [13C2,15N3]-Tebapivat	Up to Day 21
Tmax in Plasma and Whole Blood for Total Radioactivity	Up to Day 42
Percentage of Radioactive Dose Excreted in Urine Over a Time Interval (feut1-t2) of [14C]-Tebapivat	Up to Day 42
Percentage of Radioactive Dose Excreted in Feces Over a Time Interval (fef t1-t2) of [14C]-Tebapivat	Up to Day 42
Cumulative Percentage of Radioactive Dose Excreted in Urine Over a Time Interval (Cum feut1-t2) of [14C]-Tebapivat	Up to Day 42
Cumulative Percentage of Radioactive Dose Excreted in Feces Over a Time Interval (Cum fef t1-t2) of [14C]-Tebapivat	Up to Day 42
Percentage of Total Radioactivity in Total Excreta (Feces + Urine) (Cum fe) of [14C]-Tebapivat	Up to Day 42
Amount of Drug Excreted in Urine (Aeu) of [14C]-Tebapivat	Up to Day 42
Cumulative Amount of Drug Excreted in Urine (Cum Aeu) of [14C]-Tebapivat	Up to Day 42
Renal Clearance (CLR) of [14C]-Tebapivat	Up to Day 42
Area Under the Concentration-Time Curve (AUC) From Time 0 to 168 Hours Postdose (AUC0-168) in Plasma for [14C]-Tebapivat and [13C2,15N3]-Tebapivat	Up to Day 7
AUC0-168 in Plasma and Whole Blood for Total Radioactivity	Up to Day 7
AUC From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-t) in Plasma for [14C]-Tebapivat and [13C2,15N3]-Tebapivat	Up to Day 21
AUC0-t in Plasma and Whole Blood for Total Radioactivity	Up to Day 42
AUC Extrapolated to Infinity (AUC0-inf) in Plasma for [14C]-Tebapivat and [13C2,15N3]-Tebapivat	Up to Day 21
(AUC0-inf) in Plasma and Whole Blood for Total Radioactivity	Up to Day 42
Maximum Observed Plasma Concentration (Cmax) for [14C]-Tebapivat and [13C2,15N3]-Tebapivat	Up to Day 21
Cmax in Plasma and Whole Blood for Total Radioactivity	Up to Day 42
Time to Reach Cmax (Tmax) for [14C]-Tebapivat and [13C2,15N3]-Tebapivat	Up to Day 21
Ratio of Dose-Normalized AUC0-inf of Oral Administration of [14C]-Tebapivat Relative to IV Administration of [13C2,15N3]-Tebapivat	Up to Day 21
Quantitation of Major Metabolites of [14C]-Tebapivat in Plasma After Oral Administration	Up to Day 21	Quantification of major metabolites of \[14C\]-tebapivat in plasma.
Quantitation of Major Metabolites of [14C]-Tebapivat in Excreta After Oral Administration	Up to Day 42	Quantification of major metabolites of \[14C\]-tebapivat in excreta.
Identification of Chemical Structure of Major Metabolites of [14C]-Tebapivat in Plasma After Oral Administration	Up to Day 21	Identification of the chemical structures of major metabolites of \[14C\]-tebapivat in plasma.
Identification of Chemical Structure of Major Metabolites of [14C]-Tebapivat in Excreta After Oral Administration	Up to Day 42	Identification of the chemical structures of major metabolites of \[14C\]-tebapivat in excreta.

Secondary Outcome Measures

Name	Time	Method
Number of Participants with Adverse Events (AEs) by Type, Severity, and Relationship to Study Drug	Up to Day 28
Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Assessments	Baseline up to Day 28
Number of Participants With Clinically Significant Change From Baseline in Abnormal 12-Lead Electrocardiogram (ECG) Parameters	Baseline up to Day 28
Number of Participants With Clinically Significant Change From Baseline in Abnormal Vital Signs Measurements	Baseline up to Day 28

Trial Locations

Locations (1)

Taha El-Shahat; 🇺🇸 Madison, Wisconsin, United States