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

NCT06745271 | Completed Phase 1 FDA Drug

• 1 other identifier: AG946-C-004
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Participants

Outcome Measures

Primary Outcomes (30)

• 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

• Tmax in Plasma and Whole Blood for Total Radioactivity

  Up to Day 42

• Terminal Elimination Half-Life (t1/2) in Plasma for [14C]-Tebapivat and [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

• 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

• 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

  Quantification of major metabolites of \[14C\]-tebapivat in plasma.

  Up to Day 21

• Quantitation of Major Metabolites of [14C]-Tebapivat in Excreta After Oral Administration

  Quantification of major metabolites of \[14C\]-tebapivat in excreta.

  Up to Day 42

• Identification of Chemical Structure of Major Metabolites of [14C]-Tebapivat in Plasma After Oral Administration

  Identification of the chemical structures of major metabolites of \[14C\]-tebapivat in plasma.

  Up to Day 21

• Identification of Chemical Structure of Major Metabolites of [14C]-Tebapivat in Excreta After Oral Administration

  Identification of the chemical structures of major metabolites of \[14C\]-tebapivat in excreta.

  Up to Day 42

Secondary Outcomes (4)

• 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

Study Arms (1)

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

EXPERIMENTAL

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.

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

Interventions

[14C]-tebapivat DRUG

Oral Capsule

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

[13C2,15N3]-tebapivat DRUG

Intravenous Solution

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

Eligibility Criteria

• Age: 18 Years - 55 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male, of any race, between 18 and 55 years of age, inclusive.
• a. Males must agree to use contraception.
• 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.
• 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.
• History of a minimum of 1 bowel movement per day.
• Able to comprehend and are willing to sign the informed consent form (ICF) and abide by the study restrictions.

You may not qualify if:

• 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, as determined 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 are allowed; cholecystectomy is not allowed).
• Positive hepatitis panel and/or positive human immunodeficiency virus test. Participants whose results are compatible with prior immunization may be included.
• Administration of any vaccine within 30 days prior to dosing.
• 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.
• 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.
• 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.
• 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.
• 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.
• Have previously completed or withdrawn from this study or any other study investigating tebapivat and have previously received tebapivat.
• 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.
• 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.
• Positive urine drug screen at screening or positive alcohol test result or positive urine drug screen at check-in.
• History of alcoholism or drug/chemical abuse within 2 years prior to check-in.

Sponsors & Collaborators

• Agios Pharmaceuticals, Inc.: lead

Study Sites (1)

Taha El-Shahat

Madison, Wisconsin, 53704, United States

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2024
• First Posted: December 20, 2024
• Study Start: December 20, 2024
• Primary Completion: February 21, 2025
• Study Completion: February 21, 2025
• Last Updated: March 18, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)