Nonalcoholic Steatohepatitis (NASH)Phase 1HINCT02891408

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

A Phase 1 study testing Firsocostat and Fenofibrate in people with Nonalcoholic Steatohepatitis (NASH), run by Gilead Sciences at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 70 yearsHealthy volunteers can take part
Conditions the study is for: Nonalcoholic Steatohepatitis (NASH)
What is being tested?: Firsocostat and Fenofibrate
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 74 participants
Where: 5 sitesUnited States
Study dates: 23 Sep 2016to 13 May 2019
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 70 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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):

Show all 21Show fewer

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.

Who cannot join

None listed.

Trial locations and contacts

5 sites in 1 country.

City, postcode or hospital

5 sites in 1 country

United States5 sites

Study site
Miami, Florida
Study site
Minneapolis, Minnesota
Study site
Orlando, Florida
Study site
San Antonio, Texas
Study site
Tustin, California

Other trials in United States

About this study

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

Conditions: Nonalcoholic Steatohepatitis (NASH)
Being tested: Firsocostat, Fenofibrate
Medical subject headings: Non-alcoholic Fatty Liver Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

FirsocostatDrug
Also called GS-0976
Capsule(s) administered orally on Day 1
FenofibrateDrug
Tablet administered orally on Day 1

Study groups in NCT02891408
Study group	Role	What they receive
Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg	Experimental	Participants with mild hepatic impairment will receive a single dose of firsocostat 20 mg (2 × 10 mg capsules). Receives: Drug: Firsocostat
Cohort 1 (Normal Hepatic Function): Firsocostat 20 mg	Experimental	Matched normal hepatic function participants to mild hepatic impairment participants will receive a single dose of firsocostat 20 mg (2 × 10 mg capsules). Receives: Drug: Firsocostat
Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg	Experimental	Participants with moderate hepatic impairment will receive a single dose of firsocostat 20 mg (2 × 10 mg capsules). Receives: Drug: Firsocostat
Cohort 2 (Normal Hepatic Function): Firsocostat 20 mg	Experimental	Matched normal hepatic function participants to moderate hepatic impairment participants will receive a single dose of firsocostat 20 mg (2 × 10 mg capsules). Receives: Drug: Firsocostat
Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg	Experimental	Participants with severe hepatic impairment will receive a single dose of firsocostat 5 mg (1 × 5 mg capsule). Receives: Drug: Firsocostat
Cohort 3 (Normal Hepatic Function) Firsocostat 5 mg	Experimental	Matched normal hepatic function participants to severe hepatic impairment participants will receive a single dose of firsocostat 5 mg (1 × 5 mg capsule). Receives: Drug: Firsocostat
Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg	Experimental	Participants with mild hepatic impairment will receive a single dose of fenofibrate 48 mg (1 × 48 mg tablet). Receives: Drug: Fenofibrate
Cohort 4 (Normal Hepatic Function) Fenofibrate 48 mg	Experimental	Matched normal hepatic function participants to mild hepatic impairment participants, will receive a single dose of fenofibrate 48 mg (1 × 48 mg tablet). Receives: Drug: Fenofibrate

What is being measured

The primary outcome is the main question the study is designed to answer.

Pharmacokinetic (PK) Parameter: AUClast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate)
AUClast is defined as the concentration of drug from time zero to the last observable concentration. The PK of fenofibric acid was evaluated in participants with mild hepatic impairment and matched participants with normal hepatic function (Cohort 4).
Measured: 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)
PK Parameter: AUCinf of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate)
AUCinf is defined as the concentration of drug extrapolated to infinite time. The PK of fenofibric acid was evaluated in participants with mild hepatic impairment and matched participants with normal hepatic function (Cohort 4).
Measured: 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)
PK Parameter: Cmax of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate)
Cmax is defined as the maximum observed concentration of drug. The PK of fenofibric acid was evaluated in participants with mild hepatic impairment and matched participants with normal hepatic function (Cohort 4).
Measured: 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)
PK Parameter: % AUCexp of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate)
%AUCexp is defined as the percentage of AUC extrapolated between AUClast and AUCinf. The PK of fenofibric acid was evaluated in participants with mild hepatic impairment and matched participants with normal hepatic function (Cohort 4).
Measured: 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)
PK Parameter: Tmax of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate)
Tmax is defined as the time (observed time point) of Cmax. The PK of fenofibric acid was evaluated in participants with mild hepatic impairment and matched participants with normal hepatic function (Cohort 4).
Measured: 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)
PK Parameter: Clast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate)
Clast is defined as the last observed quantifiable concentration of drug. The PK of fenofibric acid was evaluated in participants with mild hepatic impairment and matched participants with normal hepatic function (Cohort 4).
Measured: 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)
PK Parameter: Tlast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate)
Tlast is defined as the time (observed time point) of Clast. The PK of fenofibric acid was evaluated in participants with mild hepatic impairment and matched participants with normal hepatic function (Cohort 4).
Measured: 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)
PK Parameter: λz of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate)
λz is defined as the terminal elimination rate constant, estimated by linear regression of the terminal elimination phase of the log plasma concentration of drug versus time curve of the drug. The PK of fenofibric acid was evaluated in participants with mild hepatic impairment and matched participants with normal hepatic function (Cohort 4).
Measured: 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)
PK Parameter: CL/F of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate)
CL/F is defined as the apparent oral clearance following administration of the drug. The PK of fenofibric acid was evaluated in participants with mild hepatic impairment and matched participants with normal hepatic function (Cohort 4).
Measured: 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)
PK Parameter: Vz/F of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate)
Vz/F is defined as the apparent volume of distribution of the drug. The PK of fenofibric acid was evaluated in participants with mild hepatic impairment and matched participants with normal hepatic function (Cohort 4).
Measured: 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)
PK Parameter: t1/2 of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate)
t1/2 is defined as the estimate of the terminal elimination half-life of the drug. The PK of fenofibric acid was evaluated in participants with mild hepatic impairment and matched participants with normal hepatic function (Cohort 4).
Measured: 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 (2)

Percentage of Participants Experiencing Treatment-Emergent Adverse Events (AEs)
Treatment-emergent adverse events (TEAEs) were defined as 1 or both of the following:
- Any AEs with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug. If the AE onset date is the same as the date of study drug start date then the AE onset time must be on or after the study drug start time. If the AE onset time is missing when the start dates are the same, the AE will be considered treatment emergent.
- Any AEs leading to premature discontinuation of study drug.
Measured: First dose date plus 30 days
Percentage of Participants Experiencing Laboratory Abnormalities
Treatment-emergent laboratory abnormalities are defined as values that increase at least 1 toxicity grade from predose at any postdose visit, up to and including the date of last dose of study drug plus 30 days for subjects who permanently discontinued study drug. The most severe graded abnormality from all tests was counted for each participant.
Measured: First dose date plus 30 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

23 Sep 201613 May 2019

First posted7 Sep 2016 (estimated)
Study start23 Sep 2016
Primary completion5 May 2019
Study completion13 May 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Nonalcoholic Steatohepatitis (NASH)Studies of the same condition, open and under way.
More trials run by Gilead SciencesThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 74 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02891408
Sponsor's protocol ID: GS-US-426-3988
Acronym: HI
Status last verified: Nov 2020
First submitted: 1 Sep 2016
Last updated: 17 Dec 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

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.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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All Nonalcoholic Steatohepatitis (NASH) trials

Study at a glance

From the registry record, last updated by the sponsor on 17 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT02891408
Acronym / sponsor ID: HI / GS-US-426-3988
Conditions: Nonalcoholic Steatohepatitis (NASH)
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 74 participants (actual)
Lead sponsor: Gilead SciencesIndustry (pharma, biotech, devices)
Study start: 23 Sep 2016 (actual)
Primary completion: 5 May 2019 (actual)
Study completion: 13 May 2019 (actual)
First posted: 7 Sep 2016 (estimated)
Results: Posted 17 Dec 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 8

Arm	Type	Receives
Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg	Experimental	Drug: FirsocostatParticipants with mild hepatic impairment will receive a single dose of firsocostat 20 mg (2 × 10 mg capsules).
Cohort 1 (Normal Hepatic Function): Firsocostat 20 mg	Experimental	Drug: FirsocostatMatched normal hepatic function participants to mild hepatic impairment participants will receive a single dose of firsocostat 20 mg (2 × 10 mg capsules).
Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg	Experimental	Drug: FirsocostatParticipants with moderate hepatic impairment will receive a single dose of firsocostat 20 mg (2 × 10 mg capsules).
Cohort 2 (Normal Hepatic Function): Firsocostat 20 mg	Experimental	Drug: FirsocostatMatched normal hepatic function participants to moderate hepatic impairment participants will receive a single dose of firsocostat 20 mg (2 × 10 mg capsules).
Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg	Experimental	Drug: FirsocostatParticipants with severe hepatic impairment will receive a single dose of firsocostat 5 mg (1 × 5 mg capsule).
Cohort 3 (Normal Hepatic Function) Firsocostat 5 mg	Experimental	Drug: FirsocostatMatched normal hepatic function participants to severe hepatic impairment participants will receive a single dose of firsocostat 5 mg (1 × 5 mg capsule).
Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg	Experimental	Drug: FenofibrateParticipants with mild hepatic impairment will receive a single dose of fenofibrate 48 mg (1 × 48 mg tablet).
Cohort 4 (Normal Hepatic Function) Fenofibrate 48 mg	Experimental	Drug: FenofibrateMatched normal hepatic function participants to mild hepatic impairment participants, will receive a single dose of fenofibrate 48 mg (1 × 48 mg tablet).

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (21 listed)

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).
Male and non-pregnant/non-lactating females with moderately impaired and normal hepatic function.

Key exclusion criteria (0 listed)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
FirsocostatAlso: GS-0976Capsule(s) administered orally on Day 1	Drug	Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg, Cohort 1 (Normal Hepatic Function): Firsocostat 20 mg, Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg, Cohort 2 (Normal Hepatic Function): Firsocostat 20 mg, Cohort 3 (Normal Hepatic Function) Firsocostat 5 mg, Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg
FenofibrateTablet administered orally on Day 1	Drug	Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg, Cohort 4 (Normal Hepatic Function) Fenofibrate 48 mg

Primary outcome

Pharmacokinetic (PK) Parameter: AUClast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate)
Time frame: 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)
AUClast is defined as the concentration of drug from time zero to the last observable concentration. The PK of fenofibric acid was evaluated in participants with mild hepatic impairment and matched participants with normal hepatic function (Cohort 4).
PK Parameter: AUCinf of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate)
Time frame: 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)
AUCinf is defined as the concentration of drug extrapolated to infinite time. The PK of fenofibric acid was evaluated in participants with mild hepatic impairment and matched participants with normal hepatic function (Cohort 4).
PK Parameter: Cmax of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate)
Time frame: 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)
Cmax is defined as the maximum observed concentration of drug. The PK of fenofibric acid was evaluated in participants with mild hepatic impairment and matched participants with normal hepatic function (Cohort 4).
PK Parameter: % AUCexp of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate)
Time frame: 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)
%AUCexp is defined as the percentage of AUC extrapolated between AUClast and AUCinf. The PK of fenofibric acid was evaluated in participants with mild hepatic impairment and matched participants with normal hepatic function (Cohort 4).
PK Parameter: Tmax of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate)
Time frame: 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)
Tmax is defined as the time (observed time point) of Cmax. The PK of fenofibric acid was evaluated in participants with mild hepatic impairment and matched participants with normal hepatic function (Cohort 4).
PK Parameter: Clast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate)
Time frame: 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)
Clast is defined as the last observed quantifiable concentration of drug. The PK of fenofibric acid was evaluated in participants with mild hepatic impairment and matched participants with normal hepatic function (Cohort 4).
PK Parameter: Tlast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate)
Time frame: 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)
Tlast is defined as the time (observed time point) of Clast. The PK of fenofibric acid was evaluated in participants with mild hepatic impairment and matched participants with normal hepatic function (Cohort 4).
PK Parameter: λz of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate)
Time frame: 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)
λz is defined as the terminal elimination rate constant, estimated by linear regression of the terminal elimination phase of the log plasma concentration of drug versus time curve of the drug. The PK of fenofibric acid was evaluated in participants with mild hepatic impairment and matched participants with normal hepatic function (Cohort 4).
PK Parameter: CL/F of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate)
Time frame: 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)
CL/F is defined as the apparent oral clearance following administration of the drug. The PK of fenofibric acid was evaluated in participants with mild hepatic impairment and matched participants with normal hepatic function (Cohort 4).
PK Parameter: Vz/F of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate)
Time frame: 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)
Vz/F is defined as the apparent volume of distribution of the drug. The PK of fenofibric acid was evaluated in participants with mild hepatic impairment and matched participants with normal hepatic function (Cohort 4).
PK Parameter: t1/2 of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate)
Time frame: 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)
t1/2 is defined as the estimate of the terminal elimination half-life of the drug. The PK of fenofibric acid was evaluated in participants with mild hepatic impairment and matched participants with normal hepatic function (Cohort 4).

2 secondary outcomes

Percentage of Participants Experiencing Treatment-Emergent Adverse Events (AEs)
Time frame: First dose date plus 30 days
Percentage of Participants Experiencing Laboratory Abnormalities
Time frame: First dose date plus 30 days

Results and safety

Results posted to the registry on 17 Dec 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg	10	10
Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg	10	10
Cohort 1 & 2 (Normal Hepatic Function): Firsocostat 20 mg	14	13
Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg	10	10
Cohort 3 (Normal Hepatic Function) Firsocostat 5 mg	10	10
Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg	10	10
Cohort 4 (Normal Hepatic Function) Fenofibrate 48 mg	10	10

Primary outcome: Pharmacokinetic (PK) Parameter: AUClast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate)

Time frame: 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). Mean (Standard Deviation). Unit: hr*ng/mL

Measure	Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg n = 10	Cohort 1 (Normal Hepatic Function): Firsocostat 20 mg n = 10	Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg n = 10	Cohort 2 (Normal Hepatic Function): Firsocostat 20 mg n = 10	Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg n = 10	Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg n = 10	Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg n = 10	Cohort 4 (Normal Hepatic Function): Fenofibrate 48 mg n = 10
Firsocostat	160.6 (158.28)	69.8 (38.73)	682.1 (497.09)	64.5 (33.22)	310.4 (75.18)	10.2 (2.92)	–	–
GS-834773	46.2 (57.67)	7.4 (5.83)	395.8 (535.93)	5.1 (3.21)	153.3 (65.72)	1.4 (1.38)	–	–
Fenofibric Acid	–	–	–	–	–	–	61207.4 (24630.23)	48128.0 (17377.69)

Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg vs Cohort 1 (Normal Hepatic Function): Firsocostat 20 mg: Geometric least-square mean (GLSM) ratio: 181 (90% CI 98 to 332)
Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg vs Cohort 2 (Normal Hepatic Function): Firsocostat 20 mg: GLSM ratio: 881 (90% CI 488 to 1589)
Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg vs Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg: GLSM ratio: 3081 (90% CI 2446 to 3881)

Population analysed: PK Analysis Sets included all enrolled participants who took at least 1 dose of study drug and had at least 1 nonmissing postdose concentration value reported by PK laboratory for corresponding analytes. 6 participants with normal hepatic function served as matched controls across both Cohort 1 and 2.

Primary outcome: PK Parameter: AUCinf of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate)

Measure	Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg n = 10	Cohort 1 (Normal Hepatic Function): Firsocostat 20 mg n = 10	Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg n = 10	Cohort 2 (Normal Hepatic Function): Firsocostat 20 mg n = 10	Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg n = 10	Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg n = 10	Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg n = 10	Cohort 4 (Normal Hepatic Function): Fenofibrate 48 mg n = 10
Firsocostat	165.2 (162.71)	70.5 (38.82)	686.6 (499.35)	65.8 (34.36)	313.6 (72.68)	10.6 (2.97)	–	–
GS-834773	48.5 (59.21)	8.2 (5.84)	399.0 (537.09)	5.9 (3.46)	155.9 (65.85)	1.6 (1.37)	–	–
Fenofibric Acid	–	–	–	–	–	–	65530.7 (25917.76)	50754.1 (18262.73)

Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg vs Cohort 1 (Normal Hepatic Function): Firsocostat 20 mg: GLSM ratio: 183 (90% CI 100 to 337)
Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg vs Cohort 2 (Normal Hepatic Function): Firsocostat 20 mg: GLSM ratio: 869 (90% CI 482 to 1568)
Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg vs Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg: GLSM ratio: 2976 (90% CI 2389 to 3708)

Population analysed: Participants in the PK Analysis Sets were analyzed. 6 participants with normal hepatic function served as matched controls across both Cohort 1 and 2.

Primary outcome: PK Parameter: Cmax of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate)

Measure	Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg n = 10	Cohort 1 (Normal Hepatic Function): Firsocostat 20 mg n = 10	Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg n = 10	Cohort 2 (Normal Hepatic Function): Firsocostat 20 mg n = 10	Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg n = 10	Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg n = 10	Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg n = 10	Cohort 4 (Normal Hepatic Function): Fenofibrate 48 mg n = 10
Firsocostat	50.9 (45.96)	25.4 (20.44)	197.7 (118.67)	20.1 (12.09)	73.8 (17.70)	3.0 (1.56)	–	–
GS-834773	12.9 (16.08)	2.3 (2.11)	77.3 (56.03)	1.4 (1.16)	31.3 (14.66)	0.5 (0.64)	–	–
Fenofibric Acid	–	–	–	–	–	–	2723.0 (1078.36)	2451.0 (808.68)

Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg vs Cohort 1 (Normal Hepatic Function): Firsocostat 20 mg: GLSM ratio: 169 (90% CI 87 to 326)
Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg vs Cohort 2 (Normal Hepatic Function): Firsocostat 20 mg: GLSM ratio: 905 (90% CI 537 to 1526)
Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg vs Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg: GLSM ratio: 2719 (90% CI 1994 to 3708)

Population analysed: Participants in the PK Analysis Sets were analyzed. 6 participants with normal hepatic function served as matched controls across both Cohort 1 and 2.

Primary outcome: PK Parameter: % AUCexp of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate)

Measure	Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg n = 10	Cohort 1 (Normal Hepatic Function): Firsocostat 20 mg n = 10	Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg n = 10	Cohort 2 (Normal Hepatic Function): Firsocostat 20 mg n = 10	Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg n = 10	Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg n = 10	Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg n = 10	Cohort 4 (Normal Hepatic Function): Fenofibrate 48 mg n = 10
Firsocostat	2.54 (2.378)	1.36 (1.222)	0.63 (0.788)	1.92 (1.645)	1.35 (1.953)	4.68 (2.671)	–	–
GS-834773	7.16 (7.997)	13.16 (12.642)	1.71 (1.889)	13.59 (12.288)	2.21 (2.288)	25.94 (19.497)	–	–
Fenofibric Acid	–	–	–	–	–	–	7.11 (3.767)	5.38 (2.758)

Population analysed: Participants in the PK Analysis Sets were analyzed. 6 participants with normal hepatic function served as matched controls across both Cohort 1 and 2.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: First dose date plus 30 days. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg	0 of 10 (0%)	2 of 10 (20%)	0 of 10
Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg	0 of 10 (0%)	1 of 10 (10%)	0 of 10
Cohort 1 & 2 (Normal Hepatic Function): Firsocostat 20 mg	0 of 14 (0%)	1 of 14 (7.1%)	0 of 14
Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg	0 of 10 (0%)	3 of 10 (30%)	0 of 10
Cohort 3 (Normal Hepatic Function) Firsocostat 5 mg	0 of 10 (0%)	1 of 10 (10%)	0 of 10
Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg	0 of 10 (0%)	0 of 10 (0%)	0 of 10
Cohort 4 (Normal Hepatic Function) Fenofibrate 48 mg	0 of 10 (0%)	1 of 10 (10%)	0 of 10

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publicationNelson 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.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Gilead Study Director study director

Gilead Sciences

5 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Firsocostat and Fenofibrate in people with Nonalcoholic Steatohepatitis (NASH), run by Gilead Sciences at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pharmacokinetic (PK) Parameter: AUClast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) (time frame: 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)). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02891408, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2020.