A Trial to Examine the Interaction of Repinatrabit With Ethinyl Estradiol/Norethindrone, Metformin,Carbamazepine, Rosuvastatin, and Methotrexate When Administered Together

NCT07446400 | Recruiting Phase 1 FDA Drug

• 1 other identifier: 359-201-00015
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the drug-drug interaction (DDI) of repinatrabit with ethinyl estradiol/norethindrone or norethisterone (EE/NE), metformin, rosuvastatin, carbamazepine, and methotrexate in healthy participants.

Conditions

Healthy Volunteers

Keywords

Phenylketonuria; Drug-Drug Interaction (DDI) study

Outcome Measures

Primary Outcomes (3)

• All Arms: Maximum Plasma Concentration (Cmax)

  Cmax will be assessed for EE/NE in Arm 1, metformin and rosuvastatin in Arm 2, repinatrabit in Arm 3, and methotrexate in Arm 4 in this outcome measure

  Arm 1: up to Day 19; Arm 2: up to Day 10; Arm 3: up to Day 16; Arm 4: up to Day 9

• All Arms: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Observable Concentration at Time t (AUCt)

  AUCt will be assessed for EE/NE in Arm 1, metformin and rosuvastatin in Arm 2, repinatrabit in Arm 3, and methotrexate in Arm 4 in this outcome measure.

  Arm 1: up to Day 19; Arm 2: up to Day 10; Arm 3: up to Day 16; Arm 4: up to Day 9

• All Arms: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinfinity)

  AUCinfinity will be assessed for EE/NE in Arm 1, metformin and rosuvastatin in Arm 2, repinatrabit in Arm 3, and methotrexate in Arm 4 in this outcome measure.

  Arm 1: up to Day 19; Arm 2: up to Day 10; Arm 3: up to Day 16; Arm 4: up to Day 9

Secondary Outcomes (8)

• All Arms: Number of Participants With Treatment Emergent Adverse Events (TEAEs)

  Arm 1: up to Day 25; Arm 2: up to Day 16; Arm 3: up to Day 22; Arm 4: up to Day 15

• All Arms: Number of Participants With Potentially Clinically Relevant Changes in 12-Lead Electrocardiogram (ECG) Tests

  Arm 1: up to Day 19; Arm 2: up to Day 10; Arm 3: up to Day 16; Arm 4: up to Day 9

• All Arms: Number of Participants With Potentially Clinically Relevant Changes in Vital Signs

  Arm 1: up to Day 19; Arm 2: up to Day 10; Arm 3: up to Day 16; Arm 4: up to Day 9

• All Arms: Number of Participants With Potentially Clinically Relevant Changes in Clinical Laboratory Tests

  Arm 1: up to Day 19; Arm 2: up to Day 10; Arm 3: up to Day 16; Arm 4: up to Day 9

• All Arms: Time to Maximum (Peak) Plasma Concentration (Tmax)

  Arm 1: up to Day 19; Arm 2: up to Day 10; Arm 3: up to Day 16; Arm 4: up to Day 9

Study Arms (4)

Arm 1: Repinatrabit + EE/NE

EXPERIMENTAL

Participants will first receive a single dose of EE/NE, orally, followed by repinatrabit in combination with EE/NE or alone, up to Day 18.

Drug: Repinatrabit; Drug: EE/NE

Arm 2: Repinatrabit + (Metformin + Rosuvastatin)

EXPERIMENTAL

Participants will receive a single dose of metformin and rosuvastatin, orally, followed by repinatrabit in combination with metformin and rosuvastatin or alone, up to Day 9.

Drug: Repinatrabit; Drug: Metformin; Drug: Rosuvastatin

Arm 3: Repinatrabit + Carbamazepine

EXPERIMENTAL

Participants will receive a single dose of repinatrabit, orally, followed by carbamazepine in combination with repinatrabit or alone, up to Day 15.

Drug: Repinatrabit; Drug: Carbamazepine

Arm 4: Repinatrabit + Methotrexate

EXPERIMENTAL

Participants will receive a single dose of methotrexate, orally, followed by repinatrabit in combination with methotrexate or alone, up to Day 8.

Drug: Repinatrabit; Drug: Methotrexate

Interventions

Repinatrabit DRUG

Oral tablet.

Also known as: JNT517

Arm 1: Repinatrabit + EE/NE; Arm 2: Repinatrabit + (Metformin + Rosuvastatin); Arm 3: Repinatrabit + Carbamazepine; Arm 4: Repinatrabit + Methotrexate

EE/NE DRUG

Oral tablet.

Arm 1: Repinatrabit + EE/NE

Metformin DRUG

Oral tablet.

Arm 2: Repinatrabit + (Metformin + Rosuvastatin)

Rosuvastatin DRUG

Oral tablet.

Arm 2: Repinatrabit + (Metformin + Rosuvastatin)

Methotrexate DRUG

Oral tablet.

Arm 4: Repinatrabit + Methotrexate

Carbamazepine DRUG

Oral tablet.

Arm 3: Repinatrabit + Carbamazepine

Eligibility Criteria

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

You may qualify if:

• Body mass index (BMI) from 18 to 35 kilograms per square meter (kg/m\^2) (inclusive).
• Male and female (of non-childbearing potential) assigned at birth, inclusive of all gender identities. Arm 1 will only recruit biological females.
• In good health as determined by:
• Medical history
• Physical examination
• ECG
• Serum chemistry, urinalysis, hematology, and serology tests
• Willing to stay in the clinic for the required period and willing to be contacted for the safety follow-up via telephone contact.
• Ability to provide written, informed consent prior to initiation of any trial-related procedures, and ability, in the opinion of the principal investigator, to comply with all the requirements of the trial.

You may not qualify if:

• Female participants of childbearing potential.
• Female participants who have used HRT within 60 days or hormonal contraceptives within 14 days prior to Day 1 (Arm 1 only).
• Clinically significant abnormality in past medical history, or at the screening physical examination, that in the investigator's or sponsor's opinion may place the participant at risk or interfere with outcome variables including absorption, distribution, metabolism, and excretion of drug. This includes, but is not limited to, history of or concurrent cardiac, hepatic, renal, neurologic, endocrine, gastrointestinal, respiratory, hematologic, and immunologic disease or cholecystectomy.
• For Arm 3, participants who test positive for HLA haplotypes associated with carbamazepine-induced hypersensitivity (HLA-B\*15:02, HLA-A\*31:01, and HLA-B\*15:11).

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead

Study Sites (1)

Nucleus Network

Melbourne, Victoria, 3004, Australia

RECRUITING

Related Links

• Otsuka Clinical Trials website
• Otsuka Clinical Trial Transparency

MeSH Terms

Conditions

Phenylketonurias

Interventions

Metformin; Rosuvastatin Calcium; Methotrexate; Carbamazepine

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Sulfonamides; Amides; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Dibenzazepines; Heterocyclic Compounds, 3-Ring

Central Study Contacts

Otsuka Call Center

CONTACT

844-687-8522; Otsuka-ProfessionalServices@otsuka-us.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2026
• First Posted: March 3, 2026
• Study Start: March 31, 2026
• Primary Completion: June 9, 2026
• Study Completion: June 15, 2026
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Data will be available after marketing approval in global markets, or beginning 1-3 years following article publication. There is no end date to the availability of the data.
• Access Criteria: Otsuka will share data on the Vivli data sharing platform: https://vivli.org/ourmember/Otsuka/

Locations

AU (1)