A Trial to Examine if Repinatrabit is Processed Differently in Adults With Reduced Liver or Kidney Function Compared to Adults With Normal Liver and Kidney Function

A Phase 1, Open-label, Single-dose, Parallel-group Study Evaluating the Pharmacokinetics of Oral Repinatrabit (JNT-517) Immediate Release Tablet in Hepatic or Renal Impaired Adult Participants Matched to Adult Participants With Normal Hepatic and Renal Function

This trial is intended to understand how the body processes repinatrabit in people with moderate liver impairment and severe kidney impairment and also to compare these results with people of similar age, weight, and sex who have normal liver function.

Study Overview

• Status: Recruiting
• Conditions: Phenylketonuria
• Intervention / Treatment: Drug: Repinatrabit

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Otsuka Call Center; Phone Number: 844-687-8522; Email: Otsuka-ProfessionalServices@otsuka-us.com

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33014
      • Recruiting
      • Panax Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion criteria:

1. Body mass index (BMI) from 18.0 to 38.0 kilograms per square meter (kg/m^2) (inclusive).
2. Able to provide written, informed consent.
3. Male participants and female participants of childbearing potential (POCBP) must agree to remain fully abstinent from intercourse where pregnancy can occur OR practice 2 different contraceptive methods, where at least one must be highly effective.
4. Otherwise be in generally good health.

5. Additional criteria for Group 1:

   i. Have moderate hepatic impairment determined using Child-Pugh classification (Class B).

   ii. Have relatively stable hepatic function for the duration of the study as determined by the investigator and liver function test at the time of screening or stable hepatic function 1 year prior to screening.

   iii. Have normal renal function. iv. Have a clinical diagnosis of hepatic cirrhosis based on biopsy and/or clinical criteria.

6. Additional criteria for Group 2:

   i. Have estimated glomerular filtration rate based on the Chronic Kidney Disease-Epidemiology Collaboration (eGFRCKD-EPI) lesser than (<) 30 milliliters per minute per 1.73 square meters (mL/min/1.73 m^2) indicating severe renal impairment.

ii. Not currently be on dialysis. iii. Have relatively stable renal function as determined by eGFRCKD-EPI. 7) Additional criteria for Group 3: i. eGFRCKD-EPI greater than or equal to (≥) 90 mL/min/1.73 m^2 indicating normal renal function.

ii. Have liver enzymes within normal limits.

Exclusion criteria:

1. Participants who are breastfeeding.
2. Participants who have a positive pregnancy test result prior to receiving the investigational medical product (IMP).
3. Participants with international normalized ratio (INR) greater than (>) 2.3. Participants with hepatic impairment with elevated INR will be excluded based on the investigator's discretion.
4. Participants with hepatic carcinoma or porto-hepatic shunts that have been surgically created or planted.
5. A history of difficulty in obtaining intravenous access.
6. The donation of blood or plasma > 250 milliliters (mL) within 30 days prior to screening or received > 50 mL of blood or plasma within 30 days prior to screening.
7. Participants who have taken an investigational drug within 30 days prior to screening.
8. Exposure to any substances known to stimulate hepatic microsomal enzymes within 30 days prior to screening (eg, occupational exposure to pesticides, organic solvents, etc).
9. Any participant who, in the opinion of the investigator, should not participate in the trial.
10. Previous exposure to repinatrabit.
11. Additional criteria for Group 1: History of serious mental disorder including participants who have greater than Grade 1 encephalopathy as assessed by the Child-Pugh score and/or the investigator's judgment.

12. Additional criteria for Group 2:

    i) Participants that have undergone a renal transplant. ii) Participants expected to require dialysis within 45 days. iii) Clinically significant abnormal findings in the serum chemistry, hematology, or urinalysis results obtained at screening or on Day -1, other than those associated with underlying renal conditions and other stable medical conditions consistent with the disease processes.

13. Additional criteria for Group 3: History of or current hepatitis, or carriers of hepatitis B surface antigen (HBsAg) and/or hepatitis C antibodies (anti-HC).

Note: Other protocol-specified inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: Moderate Hepatic Impairment; Participants with moderate hepatic impairment will receive a single dose of repinatrabit tablet, under fasted conditions on Day 1.	Drug: Repinatrabit; Oral tablet; Other Names: JNT-517
Experimental: Group 2: Severe Renal Impairment; Participants with severe renal impairment will receive a single dose of repinatrabit tablet, under fasted conditions on Day 1.	Drug: Repinatrabit; Oral tablet; Other Names: JNT-517
Experimental: Group 3: Matched Normal Hepatic and Renal Function; Participants matched by age, weight, and sex with normal hepatic and renal function will receive a single dose of repinatrabit tablet, under fasted conditions on Day 1.	Drug: Repinatrabit; Oral tablet; Other Names: JNT-517

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Groups 1 and 2: Unbound and Total Area Under the Concentration-Time Curve Calculated to the Last Observable Concentration at Time t (AUC0-t) of Repinatrabit	From Day 1 to Day 8
Groups 1 and 2: Unbound and Total Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Repinatrabit	From Day 1 to Day 8
Groups 1 and 2: Unbound and Total Maximum (Peak) Plasma Concentration (Cmax) of Repinatrabit	From Day 1 to Day 8

Secondary Outcome Measures

Outcome Measure	Time Frame
All Groups: Number of Participants with Treatment Emergent Adverse Events (TEAEs) and Severe Adverse Events (SAEs)	Up to Day 14
All Groups: Number of Participants With Potentially Clinically Relevant Clinical Laboratory Test Results	Up to Day 8
All Groups: Number of Participants With Potentially Clinically Relevant Changes in Vital Signs	Up to Day 8
All Groups: Number of Participants With Potentially Clinically Relevant Changes in Physical Examination Findings	Up to Day 8
All Groups: Number of Participants With Potentially Clinically Relevant Changes in 12-lead Electrocardiogram (ECG) Results	Up to Day 8

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Publications and helpful links

Helpful Links

• Otsuka Clinical Trial Website:
• Otsuka Clinical Trial Transparency:

Study record dates

Study Major Dates

• Study Start (Actual): July 17, 2026
• Primary Completion (Estimated): February 9, 2027
• Study Completion (Estimated): February 15, 2027

Study Registration Dates

• First Submitted: July 15, 2026
• First Submitted That Met QC Criteria: July 15, 2026
• First Posted (Actual): July 20, 2026

Study Record Updates

• Last Update Posted (Actual): August 12, 2026
• Last Update Submitted That Met QC Criteria: August 10, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Amino Acid Metabolism, Inborn Errors; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Phenylketonurias
• Other Study ID Numbers: 359-201-00009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.
• IPD Sharing 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.
• IPD Sharing Access Criteria: Otsuka will share data on the Vivli data sharing platform: https://vivli.org/ourmember/Otsuka/
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No