Study to Evaluate the Pharmacokinetics of Firsocostat or Fenofibrate in Adults With Normal and Impaired Hepatic Function

NCT ID: NCT02891408

Last Updated: 2020-12-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 74 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-23
• Study Completion Date: 2019-05-13

Brief Summary

The primary objectives of this study are to evaluate the single-dose pharmacokinetics (PK) of firsocostat in adults with normal hepatic function, and mild, moderate, or severe hepatic impairment and to evaluate the single-dose PK of fenofibrate in adults with normal hepatic function and mild hepatic impairment.

Conditions

Nonalcoholic Steatohepatitis (NASH)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg

Participants with mild hepatic impairment will receive a single dose of firsocostat 20 mg (2 × 10 mg capsules).

Group Type: EXPERIMENTAL

Firsocostat

Intervention Type: DRUG

Capsule(s) administered orally on Day 1

Cohort 1 (Normal Hepatic Function): Firsocostat 20 mg

Matched normal hepatic function participants to mild hepatic impairment participants will receive a single dose of firsocostat 20 mg (2 × 10 mg capsules).

Group Type: EXPERIMENTAL

Firsocostat

Intervention Type: DRUG

Capsule(s) administered orally on Day 1

Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg

Participants with moderate hepatic impairment will receive a single dose of firsocostat 20 mg (2 × 10 mg capsules).

Group Type: EXPERIMENTAL

Firsocostat

Intervention Type: DRUG

Capsule(s) administered orally on Day 1

Cohort 2 (Normal Hepatic Function): Firsocostat 20 mg

Matched normal hepatic function participants to moderate hepatic impairment participants will receive a single dose of firsocostat 20 mg (2 × 10 mg capsules).

Group Type: EXPERIMENTAL

Firsocostat

Intervention Type: DRUG

Capsule(s) administered orally on Day 1

Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg

Participants with severe hepatic impairment will receive a single dose of firsocostat 5 mg (1 × 5 mg capsule).

Group Type: EXPERIMENTAL

Firsocostat

Intervention Type: DRUG

Capsule(s) administered orally on Day 1

Cohort 3 (Normal Hepatic Function) Firsocostat 5 mg

Matched normal hepatic function participants to severe hepatic impairment participants will receive a single dose of firsocostat 5 mg (1 × 5 mg capsule).

Group Type: EXPERIMENTAL

Firsocostat

Intervention Type: DRUG

Capsule(s) administered orally on Day 1

Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg

Participants with mild hepatic impairment will receive a single dose of fenofibrate 48 mg (1 × 48 mg tablet).

Group Type: EXPERIMENTAL

Fenofibrate

Intervention Type: DRUG

Tablet administered orally on Day 1

Cohort 4 (Normal Hepatic Function) Fenofibrate 48 mg

Matched normal hepatic function participants to mild hepatic impairment participants, will receive a single dose of fenofibrate 48 mg (1 × 48 mg tablet).

Group Type: EXPERIMENTAL

Fenofibrate

Intervention Type: DRUG

Tablet administered orally on Day 1

Interventions

Firsocostat

Capsule(s) administered orally on Day 1

Intervention Type: DRUG

Fenofibrate

Tablet administered orally on Day 1

Intervention Type: DRUG

Other Intervention Names

GS-0976

Eligibility Criteria

Inclusion Criteria

Cohort 1 (Mild Hepatic Impairment):

• Male and non-pregnant/non-lactating females with mildly impaired and normal hepatic function.
• Individuals will be current non-smokers (no use of tobacco, nicotine-containing or tetrahydrocannabinol (THC)-containing products within the last 14 days).
• Each individual in the control group will be matched for age (± 10 years), gender, race, and body mass index (± 15% 18 ≤ body mass index (BMI) ≤ 36 kg/m^2) with an individual in the mild hepatic impairment group.
• Individuals with mild hepatic impairment must have a score of 5-6 on the Child-Pugh-Turcotte (CPT) Classification at screening, have diagnosis of chronic (> 6 months), and stable hepatic impairment with no clinically significant changes within 3 months (or 90 days) prior to study drug administration (Day 1).

Cohort 2 (Moderate Hepatic Impairment):

• Male and non-pregnant/non-lactating females with moderately impaired and normal hepatic function.
• Individuals will be current non-smokers (no smoking of tobacco, nicotine-containing or THC-containing products within the last 14 days).
• Each individual in the control group will be matched for age (± 10 years), gender, race, and body mass index (± 15% 18 ≤ BMI ≤ 36 kg/m^2) with an individual in the moderate hepatic impairment group.
• Individuals with moderate hepatic impairment must have a score of 7-9 on the CPT Classification at screening, have diagnosis of chronic (> 6 months), and stable hepatic impairment with no clinically significant changes within 3 months (or 90 days) prior to study drug administration (Day 1).

Cohort 3 (Severe Hepatic Impairment):

• Male and nonpregnant/non-lactating females with severely impaired and normal hepatic function.
• Individuals will be current non-smokers (no use of tobacco, nicotine-containing or THC-containing products within the last 14 days).
• Each individual in the control group will be matched for age (± 10 years), gender, race, and body mass index (± 15% 18 ≤ BMI ≤ 36 kg/m^2) with an individual in the severe hepatic impairment group.
• Individuals with severe hepatic impairment must have a score of 10-15 on the CPT Classification at screening, have diagnosis of chronic (> 6 months), and stable hepatic impairment with no clinically significant changes within 3 months (or 90 days) prior to study drug administration (Day 1).

Cohort 4 (Mild Hepatic Impairment):

• Male and non-pregnant/non-lactating females with mildly impaired and normal hepatic function.
• Individuals will be current non-smokers (no use of tobacco, nicotine-containing or THC-containing products within the last 14 days).
• Each individual in the control group will be matched for age (± 10 years), gender, race, and body mass index (± 15% 18 ≤ body mass index (BMI) ≤ 36 kg/m^2) with an individual in the mild hepatic impairment group.
• Individuals with mild hepatic impairment must have a score of 5-6 on the Child-Pugh-Turcotte (CPT) Classification at screening, have diagnosis of chronic (> 6 months), and stable hepatic impairment with no clinically significant changes within 3 months (or 90 days) prior to study drug administration (Day 1).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

Tustin, California, United States

Miami, Florida, United States

Orlando, Florida, United States

Minneapolis, Minnesota, United States

San Antonio, Texas, United States

Countries

United States

References

Nelson C, Weber E, Yue MS, Millward V, Qin AR, Marbury TC, et al. The Pharmacokinetics of GS-0976, an Acetyl-CoA Carboxylase (ACC) Inhibitor, in Subjects with Mild, Moderate, and Severe Hepatic Impairment [Abstract 1719]. Hepatology AASLD Abstracts 2018;68 (Suppl 1):979A-80A.

Reference Type: RESULT

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

GS-US-426-3988

Identifier Type: -

Identifier Source: org_study_id