Phase 1
N=74
Study to Evaluate the Pharmacokinetics of Firsocostat or Fenofibrate in Adults With Normal and Impaired Hepatic Function
Nonalcoholic Steatohepatitis (NASH)
Bottom Line
View on ClinicalTrials.gov: NCT02891408 ↗Enrolled (actual)
74
Serious AEs
0.0%
Results posted
Dec 2020
Primary outcome: Primary: Pharmacokinetic (PK) Parameter: AUClast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) — 160.6; 69.8; 682.1; 64.5 hr*ng/mL
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Firsocostat (Drug); Fenofibrate (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Gilead Sciences
- Primary completion
- May 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Pharmacokinetic (PK) Parameter: AUClast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) |
160.6; 69.8; 682.1; 64.5; 310.4; 10.2 | — |
| PRIMARY PK Parameter: AUCinf of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) |
165.2; 70.5; 686.6; 65.8; 313.6; 10.6 | — |
| PRIMARY PK Parameter: Cmax of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) |
50.9; 25.4; 197.7; 20.1; 73.8; 3.0 | — |
| PRIMARY PK Parameter: % AUCexp of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) |
2.54; 1.36; 0.63; 1.92; 1.35; 4.68 | — |
| PRIMARY PK Parameter: Tmax of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) |
1.00; 1.00; 1.00; 1.00; 1.50; 2.50 | — |
| PRIMARY PK Parameter: Clast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) |
0.20; 0.10; 0.26; 0.10; 0.23; 0.08 | — |
| PRIMARY PK Parameter: Tlast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) |
24.00; 24.00; 72.00; 24.00; 48.00; 16.00 | — |
| PRIMARY PK Parameter: λz of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) |
0.132; 0.155; 0.096; 0.136; 0.077; 0.193 | — |
| PRIMARY PK Parameter: CL/F of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) |
259318.9; 376896.2; 59482.2; 395572.3; 16969.7; 509793.4 | — |
| PRIMARY PK Parameter: Vz/F of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) |
2896998.5; 2846198.8; 592810.8; 3797739.4; 230242.5; 3079474.8 | — |
| PRIMARY PK Parameter: t1/2 of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) |
5.23; 4.39; 11.20; 5.04; 9.54; 3.93 | — |
| SECONDARY Percentage of Participants Experiencing Treatment-Emergent Adverse Events (AEs) |
20.0; 10.0; 7.1; 30.0; 10.0; 0 | — |
| SECONDARY Percentage of Participants Experiencing Laboratory Abnormalities |
100.0; 90.0; 50.0; 100.0; 50.0; 90.0 | — |
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.
Data sourced from ClinicalTrials.gov (NCT02891408). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.