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

Gilead Sciences

Status and phase: Completed; Phase 1

Conditions: Nonalcoholic Steatohepatitis (NASH)

Treatments: Drug: Fenofibrate; Drug: Firsocostat

Study type: Interventional

Funder types: Industry

Identifiers

NCT02891408

GS-US-426-3988

Details and patient eligibility

About

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.

Enrollment: 74 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Key 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).

NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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74 participants in 8 patient groups

Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg

Experimental group

Description:

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

Treatment:

Drug: Firsocostat

Cohort 1 (Normal Hepatic Function): Firsocostat 20 mg

Experimental group

Description:

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

Treatment:

Drug: Firsocostat

Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg

Experimental group

Description:

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

Treatment:

Drug: Firsocostat

Cohort 2 (Normal Hepatic Function): Firsocostat 20 mg

Experimental group

Description:

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

Treatment:

Drug: Firsocostat

Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg

Experimental group

Description:

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

Treatment:

Drug: Firsocostat

Cohort 3 (Normal Hepatic Function) Firsocostat 5 mg

Experimental group

Description:

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

Treatment:

Drug: Firsocostat

Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg

Experimental group

Description:

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

Treatment:

Drug: Fenofibrate

Cohort 4 (Normal Hepatic Function) Fenofibrate 48 mg

Experimental group

Description:

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

Treatment:

Drug: Fenofibrate