A Phase 1, Open-Label, Single-Dose Study To Evaluate The Pharmacokinetics Of Mavodelpar In Subjects With Impaired Hepatic Function

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Reneo Pharmaceuticals Inc.

Participant type

Patients, Healthy volunteers

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Not possible to specify

Trial duration

6 Jul 2023 → 20 Nov 2023

Decision date (initial)

2023-07-04

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety

Primary objective to evaluate the effect of impaired hepatic function on the single dose PK of mavodelpar (25 mg) oral capsule.

Secondary objectives 3

1. Secondary: To assess the safety and tolerability of a single dose of 25 mg mavodelpar capsule in subjects with impaired hepatic function.
2. Secondary: To evaluate the effect of impaired hepatic function on the PK of mavodelpar metabolites following a single dose of 25 mg mavodelpar.
3. Exploratory: To assess the impact of impaired hepatic function on plasma protein binding of mavodelpar.

Conditions and MedDRA coding

Impaired Hepatic Function The study will enroll as following: · Group 1 (N =10) – Normal hepatic function (healthy subjects), single dose · Group 2 (N=8) – Mild hepatic impairment (Child-Pugh A - a score of 5 to 6), single dose · Group 3 (N=8) – Moderate hepatic impairment (Child-Pugh B a score of 7 to 9), single dose · Group 4 (N=6) – Severe hepatic impairment (Child-Pugh C a score of 10 to 15), single dose Healthy volunteers with normal hepatic function.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Male and female subjects, between 18 and 70 years of age, inclusive.
2. Female subjects of childbearing potential must have negative pregnancy test results at Screening and Check-in.
3. Must agree to adhere to the contraception requirements defined in Section ‎6.4.4.
4. BMI of 18.0-40.0 kg/m2 at Screening. BMI = body weight (kg) / [height (m)]2.
5. Subjects with HI: Has impaired hepatic function as defined by the Child-Pugh classification (Appendix A) for severity of liver disease and has a Child-Pugh score in line with one of the following HI groups at Screening: Group 2; mild (Class A); Child-Pugh score 5-6, inclusive. Group 3; moderate (Class B); Child-Pugh score 7-9, inclusive. Group 4; severe (Class C); Child-Pugh score 10-15, inclusive.
6. Healthy Subjects: Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs, or ECGs, as deemed by the Investigator or designee.

Exclusion criteria 7

1. Previously received mavodelpar.
2. Female subjects of childbearing potential who are pregnant or lactating.
3. An employee or contractor of the facility conducting the study, or a family member of the Investigator, site staff, or Sponsor.
4. Administration of an investigational agent in a clinical study in the past 30 days (or 5 multiples of half-life, whichever is longer) before dosing.
5. Medical illness or other concern which would cause the Investigator to conclude that the subject will not be able to perform the study procedures or assessments or would confound interpretation of data obtained during assessment.
6. Medical history of cardiac disease and/or clinically significant ECG abnormalities.
7. Pulse rate is lower than 40 bpm or higher than 99 bpm at screening.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. AUClast, AUCinf, and Cmax for mavodelpar.

Secondary endpoints 6

1. Safety: AEs.
2. Safety: Absolute values and changes from baseline in clinical laboratory parameters (serum chemistry, hematology, coagulation, and urinalysis).
3. Safety: Absolute values and changes from baseline in vital signs (systolic/diastolic blood pressure, pulse, oral body temperature and respiratory rate).
4. Safety: Absolute values and changes from baseline in 12-lead electrocardiograms (ECGs; QT interval, heart rate corrected QT interval using Fridericia’s formula [QTcF], HR, PR, RR, and QRS).
5. Pharmacokinetics: AUClast, AUCinf, and Cmax for mavodelpar metabolites.
6. Exploratory: Fraction of unbound mavodelpar in plasma (fu) and, if applicable, PK parameters expressed in terms of unbound mavodelpar concentrations (e.g., AUCu, Cumax, and CLu/F).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Reneo Pharmaceuticals Inc.

Sponsor organisation

Reneo Pharmaceuticals Inc.

Address

18575 Jamboree Road Suite 275s

City

Irvine

Postcode

92612-2534

Country

United States

Scientific contact point

Organisation

Reneo Pharmaceuticals Inc.

Contact name

Willis Chou

Public contact point

Organisation

Reneo Pharmaceuticals Inc.

Contact name

Willis Chou

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 2 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications