Clinical trial NCT02891408: Study to Evaluate the Pharmacokinetics of Firsocostat or Fenofibrate in Adults With Normal and Impaired Hepatic Function
Official title: A Phase 1 Open-Label, Parallel-Group, Single-Dose Study to Evaluate the Pharmacokinetics of GS-0976 or Fenofibrate in Subjects With Normal and Impaired Hepatic Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Nonalcoholic Steatohepatitis (NASH)
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2016-09-07
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Pharmacokinetic (PK) Parameter: AUClast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate)
timeFrame: Day 1: 0 (predose, ≤ 5 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 96 hours postdose; or 72 hours of early termination from the study (if applicable)
measure: PK Parameter: AUCinf of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate)
timeFrame: Day 1: 0 (predose, ≤ 5 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 96 hours postdose; or 72 hours of early termination from the study (if applicable)
measure: PK Parameter: Cmax of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate)
timeFrame: Day 1: 0 (predose, ≤ 5 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 96 hours postdose; or 72 hours of early termination from the study (if applicable)
measure: PK Parameter: % AUCexp of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate)
timeFrame: Day 1: 0 (predose, ≤ 5 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 96 hours postdose; or 72 hours of early termination from the study (if applicable)
measure: PK Parameter: Tmax of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate)
timeFrame: Day 1: 0 (predose, ≤ 5 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 96 hours postdose; or 72 hours of early termination from the study (if applicable)
measure: PK Parameter: Clast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate)
timeFrame: Day 1: 0 (predose, ≤ 5 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 96 hours postdose; or 72 hours of early termination from the study (if applicable)
measure: PK Parameter: Tlast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate)
timeFrame: Day 1: 0 (predose, ≤ 5 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 96 hours postdose; or 72 hours of early termination from the study (if applicable)
measure: PK Parameter: λz of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate)
timeFrame: Day 1: 0 (predose, ≤ 5 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 96 hours postdose; or 72 hours of early termination from the study (if applicable)
measure: PK Parameter: CL/F of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate)
timeFrame: Day 1: 0 (predose, ≤ 5 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 96 hours postdose; or 72 hours of early termination from the study (if applicable)
measure: PK Parameter: Vz/F of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate)
timeFrame: Day 1: 0 (predose, ≤ 5 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 96 hours postdose; or 72 hours of early termination from the study (if applicable)
measure: PK Parameter: t1/2 of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate)
timeFrame: Day 1: 0 (predose, ≤ 5 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 96 hours postdose; or 72 hours of early termination from the study (if applicable)
Secondary outcomes:
measure: Percentage of Participants Experiencing Treatment-Emergent Adverse Events (AEs)
timeFrame: First dose date plus 30 days
measure: Percentage of Participants Experiencing Laboratory Abnormalities
timeFrame: First dose date plus 30 days
Other outcomes:
Locations:
city: Tustin
country: United States
state: California
city: Miami
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Minneapolis
country: United States
state: Minnesota
city: San Antonio
country: United States
state: Texas
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: 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.