HI: Study to Evaluate the Pharmacokinetics of Firsocostat or Fenofibrate in Adults With Normal and Impaired Hepatic Function
Sponsor
Gilead Sciences (Industry)
Overall Status
Completed
CT.gov ID
NCT02891408
Collaborator
(none)
74
5
8
31.6
14.8
0.5
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
74 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date
:
Sep 23, 2016
Actual Primary Completion Date
:
May 5, 2019
Actual Study Completion Date
:
May 13, 2019
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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). |
Drug: Firsocostat
Capsule(s) administered orally on Day 1
Other Names:
|
| Experimental: 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). |
Drug: Firsocostat
Capsule(s) administered orally on Day 1
Other Names:
|
| Experimental: 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). |
Drug: Firsocostat
Capsule(s) administered orally on Day 1
Other Names:
|
| Experimental: 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). |
Drug: Firsocostat
Capsule(s) administered orally on Day 1
Other Names:
|
| Experimental: 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). |
Drug: Firsocostat
Capsule(s) administered orally on Day 1
Other Names:
|
| Experimental: 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). |
Drug: Firsocostat
Capsule(s) administered orally on Day 1
Other Names:
|
| Experimental: 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). |
Drug: Fenofibrate
Tablet administered orally on Day 1
|
| Experimental: 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). |
Drug: Fenofibrate
Tablet administered orally on Day 1
|
Outcome Measures
Primary Outcome Measures
- Pharmacokinetic (PK) Parameter: AUClast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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).
Secondary Outcome Measures
- Percentage of Participants Experiencing Treatment-Emergent Adverse Events (AEs) [First dose date plus 30 days]
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.
- Percentage of Participants Experiencing Laboratory Abnormalities [First dose date plus 30 days]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 70 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Tustin | California | United States | ||
| 2 | Miami | Florida | United States | ||
| 3 | Orlando | Florida | United States | ||
| 4 | Minneapolis | Minnesota | United States | ||
| 5 | San Antonio | Texas | United States |
Sponsors and Collaborators
- Gilead Sciences
Investigators
- Study Director: Gilead Study Director, Gilead Sciences
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT02891408
Other Study ID Numbers:
- GS-US-426-3988
First Posted:
Sep 7, 2016
Last Update Posted:
Dec 17, 2020
Last Verified:
Nov 1, 2020
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants were enrolled at study sites in United States. The first participant was screened on 23 September 2016. The last study visit occurred on 13 May 2019. |
|---|---|
| Pre-assignment Detail | In the control groups (normal hepatic function), each participant was matched for age, gender, race, and body mass index with a participant in the hepatic impairment group. 14 total unique participants with normal hepatic function were enrolled in Cohort 1 (N = 10) and Cohort 2 (N = 4). 6 participants with normal hepatic function from Cohort 1 also served as matched controls in Cohort 2. |
| Arm/Group Title | Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg | Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg | Cohort 1 & 2 (Normal Hepatic Function): Firsocostat 20 mg | Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg | Cohort 3 (Normal Hepatic Function) Firsocostat 5 mg | Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg | Cohort 4 (Normal Hepatic Function) Fenofibrate 48 mg |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with mild hepatic impairment received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Participants with moderate hepatic impairment received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Matched normal hepatic function participants to mild or moderate hepatic impairment participants received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1 | Participants with severe hepatic impairment received a single dose of firsocostat 5 mg (1 × 5 mg capsule) orally on Day 1. | Matched normal hepatic function participants to severe hepatic impairment participants received a single dose of firsocostat 5 mg (1 × 5 mg capsule) orally on Day 1. | Participants with mild hepatic impairment received a single dose of fenofibrate 48 mg (1 × 48 mg tablet) orally on Day 1. | Matched normal hepatic function participants to mild hepatic impairment participants, received a single dose of fenofibrate 48 mg (1 × 48 mg tablet) orally on Day 1. |
| Period Title: Overall Study | |||||||
| STARTED | 10 | 10 | 14 | 10 | 10 | 10 | 10 |
| COMPLETED | 10 | 10 | 13 | 10 | 10 | 10 | 10 |
| NOT COMPLETED | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg | Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg | Cohort 1 & 2 (Normal Hepatic Function): Firsocostat 20 mg | Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg | Cohort 3 (Normal Hepatic Function) Firsocostat 5 mg | Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg | Cohort 4 (Normal Hepatic Function) Fenofibrate 48 mg | Total |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with mild hepatic impairment received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Participants with moderate hepatic impairment received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Matched normal hepatic function participants to mild or moderate hepatic impairment participants received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1 | Participants with severe hepatic impairment received a single dose of firsocostat 5 mg (1 × 5 mg capsule) orally on Day 1. | Matched normal hepatic function participants to severe hepatic impairment participants received a single dose of firsocostat 5 mg (1 × 5 mg capsule) orally on Day 1. | Participants with mild hepatic impairment received a single dose of fenofibrate 48 mg (1 × 48 mg tablet) orally on Day 1. | Matched normal hepatic function participants to mild hepatic impairment participants, received a single dose of fenofibrate 48 mg (1 × 48 mg tablet) orally on Day 1. | Total of all reporting groups |
| Overall Participants | 10 | 10 | 14 | 10 | 10 | 10 | 10 | 74 |
| Age (years) [Mean (Standard Deviation) ] | ||||||||
| Mean (Standard Deviation) [years] |
55
(8.1)
|
56
(9.1)
|
55
(8.0)
|
53
(10.8)
|
54
(8.4)
|
58
(6.4)
|
58
(5.1)
|
55
(8.0)
|
| Sex: Female, Male (Count of Participants) | ||||||||
| Female |
2
20%
|
3
30%
|
3
21.4%
|
4
40%
|
4
40%
|
3
30%
|
3
30%
|
22
29.7%
|
| Male |
8
80%
|
7
70%
|
11
78.6%
|
6
60%
|
6
60%
|
7
70%
|
7
70%
|
52
70.3%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||||||
| Hispanic or Latino |
3
30%
|
6
60%
|
7
50%
|
6
60%
|
6
60%
|
6
60%
|
6
60%
|
40
54.1%
|
| Not Hispanic or Latino |
7
70%
|
4
40%
|
7
50%
|
4
40%
|
4
40%
|
4
40%
|
4
40%
|
34
45.9%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | ||||||||
| American Indian or Alaska Native |
0
0%
|
1
10%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
1.4%
|
| Asian |
1
10%
|
0
0%
|
1
7.1%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
2.7%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
4
40%
|
0
0%
|
4
28.6%
|
1
10%
|
1
10%
|
2
20%
|
2
20%
|
14
18.9%
|
| White |
5
50%
|
9
90%
|
9
64.3%
|
9
90%
|
9
90%
|
8
80%
|
8
80%
|
57
77%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
| Title | Pharmacokinetic (PK) Parameter: AUClast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) |
|---|---|
| Description | 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). |
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | 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 (Severe Hepatic Impairment): Firsocostat 5 mg | Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg | Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg | Cohort 4 (Normal Hepatic Function): Fenofibrate 48 mg |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with mild hepatic impairment received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Matched normal hepatic function participants to mild hepatic impairment participants, received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Participants with moderate hepatic impairment received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Matched normal hepatic function participants to moderate hepatic impairment participants, received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Participants with severe hepatic impairment received a single dose of firsocostat 5 mg (1 × 5 mg capsule) orally on Day 1. | Matched normal hepatic function participants to severe hepatic impairment participants, received a single dose of firsocostat 5 mg (1 × 5 mg capsule) orally on Day 1. | Participants with mild hepatic impairment received a single dose of fenofibrate 48 mg (1 × 48 mg tablet) orally on Day 1. | Matched normal hepatic function participants to mild hepatic impairment participants, received a single dose of fenofibrate 48 mg (1 × 48 mg tablet) orally on Day 1. |
| Measure Participants | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 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)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg, Cohort 1 (Normal Hepatic Function): Firsocostat 20 mg |
|---|---|---|
| Comments | AUClast of Firsocostat | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric least-square mean (GLSM) ratio |
| Estimated Value | 181 | |
| Confidence Interval |
(2-Sided) 90% 98 to 332 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg, Cohort 2 (Normal Hepatic Function): Firsocostat 20 mg |
|---|---|---|
| Comments | AUClast of Firsocostat | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GLSM ratio |
| Estimated Value | 881 | |
| Confidence Interval |
(2-Sided) 90% 488 to 1589 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg, Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg |
|---|---|---|
| Comments | AUClast of Firsocostat | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GLSM ratio |
| Estimated Value | 3081 | |
| Confidence Interval |
(2-Sided) 90% 2446 to 3881 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg, Cohort 1 (Normal Hepatic Function): Firsocostat 20 mg |
|---|---|---|
| Comments | AUClast of GS-834773 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GLSM ratio |
| Estimated Value | 430 | |
| Confidence Interval |
(2-Sided) 90% 185 to 998 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg, Cohort 2 (Normal Hepatic Function): Firsocostat 20 mg |
|---|---|---|
| Comments | AUClast of GS-834773 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GLSM ratio |
| Estimated Value | 4417 | |
| Confidence Interval |
(2-Sided) 90% 1867 to 10449 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg, Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg |
|---|---|---|
| Comments | AUClast of GS-834773 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GLSM ratio |
| Estimated Value | 14676 | |
| Confidence Interval |
(2-Sided) 90% 7932 to 27153 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg, Cohort 4 (Normal Hepatic Function): Fenofibrate 48 mg |
|---|---|---|
| Comments | AUClast of Fenofibric Acid | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GLSM ratio |
| Estimated Value | 122 | |
| Confidence Interval |
(2-Sided) 90% 86 to 173 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | PK Parameter: AUCinf of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) |
|---|---|
| Description | 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). |
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the PK Analysis Sets were analyzed. 6 participants with normal hepatic function served as matched controls across both Cohort 1 and 2. |
| Arm/Group Title | 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 (Severe Hepatic Impairment): Firsocostat 5 mg | Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg | Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg | Cohort 4 (Normal Hepatic Function): Fenofibrate 48 mg |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with mild hepatic impairment received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Matched normal hepatic function participants to mild hepatic impairment participants, received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Participants with moderate hepatic impairment received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Matched normal hepatic function participants to moderate hepatic impairment participants, received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Participants with severe hepatic impairment received a single dose of firsocostat 5 mg (1 × 5 mg capsule) orally on Day 1. | Matched normal hepatic function participants to severe hepatic impairment participants, received a single dose of firsocostat 5 mg (1 × 5 mg capsule) orally on Day 1. | Participants with mild hepatic impairment received a single dose of fenofibrate 48 mg (1 × 48 mg tablet) orally on Day 1. | Matched normal hepatic function participants to mild hepatic impairment participants, received a single dose of fenofibrate 48 mg (1 × 48 mg tablet) orally on Day 1. |
| Measure Participants | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 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)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg, Cohort 1 (Normal Hepatic Function): Firsocostat 20 mg |
|---|---|---|
| Comments | AUCinf of Firsocostat | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GLSM ratio |
| Estimated Value | 183 | |
| Confidence Interval |
(2-Sided) 90% 100 to 337 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg, Cohort 2 (Normal Hepatic Function): Firsocostat 20 mg |
|---|---|---|
| Comments | AUCinf of Firsocostat | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GLSM ratio |
| Estimated Value | 869 | |
| Confidence Interval |
(2-Sided) 90% 482 to 1568 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg, Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg |
|---|---|---|
| Comments | AUCinf of Firsocostat | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GLSM ratio |
| Estimated Value | 2976 | |
| Confidence Interval |
(2-Sided) 90% 2389 to 3708 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg, Cohort 1 (Normal Hepatic Function): Firsocostat 20 mg |
|---|---|---|
| Comments | AUCinf of GS-834773 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GLSM ratio |
| Estimated Value | 399 | |
| Confidence Interval |
(2-Sided) 90% 179 to 892 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg, Cohort 2 (Normal Hepatic Function): Firsocostat 20 mg |
|---|---|---|
| Comments | AUCinf of GS-834773 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GLSM ratio |
| Estimated Value | 3843 | |
| Confidence Interval |
(2-Sided) 90% 1641 to 9000 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg, Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg |
|---|---|---|
| Comments | AUCinf of GS-834773 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GLSM ratio |
| Estimated Value | 10712 | |
| Confidence Interval |
(2-Sided) 90% 6525 to 17585 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg, Cohort 4 (Normal Hepatic Function): Fenofibrate 48 mg |
|---|---|---|
| Comments | AUCinf of Fenofibric Acid | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GLSM ratio |
| Estimated Value | 125 | |
| Confidence Interval |
(2-Sided) 90% 89 to 174 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | PK Parameter: Cmax of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) |
|---|---|
| Description | 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). |
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the PK Analysis Sets were analyzed. 6 participants with normal hepatic function served as matched controls across both Cohort 1 and 2. |
| Arm/Group Title | 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 (Severe Hepatic Impairment): Firsocostat 5 mg | Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg | Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg | Cohort 4 (Normal Hepatic Function): Fenofibrate 48 mg |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with mild hepatic impairment received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Matched normal hepatic function participants to mild hepatic impairment participants, received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Participants with moderate hepatic impairment received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Matched normal hepatic function participants to moderate hepatic impairment participants, received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Participants with severe hepatic impairment received a single dose of firsocostat 5 mg (1 × 5 mg capsule) orally on Day 1. | Matched normal hepatic function participants to severe hepatic impairment participants, received a single dose of firsocostat 5 mg (1 × 5 mg capsule) orally on Day 1. | Participants with mild hepatic impairment received a single dose of fenofibrate 48 mg (1 × 48 mg tablet) orally on Day 1. | Matched normal hepatic function participants to mild hepatic impairment participants, received a single dose of fenofibrate 48 mg (1 × 48 mg tablet) orally on Day 1. |
| Measure Participants | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 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)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg, Cohort 1 (Normal Hepatic Function): Firsocostat 20 mg |
|---|---|---|
| Comments | Cmax of Firsocostat | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GLSM ratio |
| Estimated Value | 169 | |
| Confidence Interval |
(2-Sided) 90% 87 to 326 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg, Cohort 2 (Normal Hepatic Function): Firsocostat 20 mg |
|---|---|---|
| Comments | Cmax of Firsocostat | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GLSM ratio |
| Estimated Value | 905 | |
| Confidence Interval |
(2-Sided) 90% 537 to 1526 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg, Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg |
|---|---|---|
| Comments | Cmax of Firsocostat | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GLSM ratio |
| Estimated Value | 2719 | |
| Confidence Interval |
(2-Sided) 90% 1994 to 3708 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg, Cohort 1 (Normal Hepatic Function): Firsocostat 20 mg |
|---|---|---|
| Comments | Cmax of GS-834773 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GLSM ratio |
| Estimated Value | 391 | |
| Confidence Interval |
(2-Sided) 90% 163 to 942 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg, Cohort 2 (Normal Hepatic Function): Firsocostat 20 mg |
|---|---|---|
| Comments | Cmax of GS-834773 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GLSM ratio |
| Estimated Value | 4470 | |
| Confidence Interval |
(2-Sided) 90% 2170 to 9207 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg, Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg |
|---|---|---|
| Comments | Cmax of GS-834773 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GLSM ratio |
| Estimated Value | 9278 | |
| Confidence Interval |
(2-Sided) 90% 4945 to 17407 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg, Cohort 4 (Normal Hepatic Function): Fenofibrate 48 mg |
|---|---|---|
| Comments | Cmax of Fenofibric Acid | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GLSM ratio |
| Estimated Value | 109 | |
| Confidence Interval |
(2-Sided) 90% 81 to 146 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | PK Parameter: % AUCexp of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) |
|---|---|
| Description | %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). |
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the PK Analysis Sets were analyzed. 6 participants with normal hepatic function served as matched controls across both Cohort 1 and 2. |
| Arm/Group Title | 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 (Severe Hepatic Impairment): Firsocostat 5 mg | Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg | Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg | Cohort 4 (Normal Hepatic Function): Fenofibrate 48 mg |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with mild hepatic impairment received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Matched normal hepatic function participants to mild hepatic impairment participants, received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Participants with moderate hepatic impairment received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1 | Matched normal hepatic function participants to moderate hepatic impairment participants, received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Participants with severe hepatic impairment received a single dose of firsocostat 5 mg (1 × 5 mg capsule) orally on Day 1. | Matched normal hepatic function participants to severe hepatic impairment participants, received a single dose of firsocostat 5 mg (1 × 5 mg capsule) orally on Day 1. | Participants with mild hepatic impairment received a single dose of fenofibrate 48 mg (1 × 48 mg tablet) orally on Day 1. | Matched normal hepatic function participants to mild hepatic impairment participants, received a single dose of fenofibrate 48 mg (1 × 48 mg tablet) orally on Day 1. |
| Measure Participants | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 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)
|
| Title | PK Parameter: Tmax of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) |
|---|---|
| Description | 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). |
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the PK Analysis Sets were analyzed. 6 participants with normal hepatic function served as matched controls across both Cohort 1 and 2. |
| Arm/Group Title | 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 (Severe Hepatic Impairment): Firsocostat 5 mg | Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg | Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg | Cohort 4 (Normal Hepatic Function): Fenofibrate 48 mg |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with mild hepatic impairment received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Matched normal hepatic function participants to mild hepatic impairment participants, received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Participants with moderate hepatic impairment received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Matched normal hepatic function participants to moderate hepatic impairment participants, received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Participants with severe hepatic impairment received a single dose of firsocostat 5 mg (1 × 5 mg capsule) orally on Day 1. | Matched normal hepatic function participants to severe hepatic impairment participants, received a single dose of firsocostat 5 mg (1 × 5 mg capsule) orally on Day 1. | Participants with mild hepatic impairment received a single dose of fenofibrate 48 mg (1 × 48 mg tablet) orally on Day 1. | Matched normal hepatic function participants to mild hepatic impairment participants, received a single dose of fenofibrate 48 mg (1 × 48 mg tablet) orally on Day 1. |
| Measure Participants | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
| Firsocostat |
1.00
|
1.00
|
1.00
|
1.00
|
1.50
|
2.50
|
||
| GS-834773 |
1.50
|
1.00
|
1.00
|
1.50
|
2.00
|
2.50
|
||
| Fenofibric Acid |
3.00
|
2.50
|
| Title | PK Parameter: Clast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) |
|---|---|
| Description | 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). |
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the PK Analysis Sets were analyzed. 6 participants with normal hepatic function served as matched controls across both Cohort 1 and 2. |
| Arm/Group Title | 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 (Severe Hepatic Impairment): Firsocostat 5 mg | Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg | Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg | Cohort 4 (Normal Hepatic Function): Fenofibrate 48 mg |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with mild hepatic impairment received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Matched normal hepatic function participants to mild hepatic impairment participants, received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Participants with moderate hepatic impairment received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Matched normal hepatic function participants to moderate hepatic impairment participants, received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Participants with severe hepatic impairment received a single dose of firsocostat 5 mg (1 × 5 mg capsule) orally on Day 1. | Matched normal hepatic function participants to severe hepatic impairment participants, received a single dose of firsocostat 5 mg (1 × 5 mg capsule) orally on Day 1. | Participants with mild hepatic impairment received a single dose of fenofibrate 48 mg (1 × 48 mg tablet) orally on Day 1. | Matched normal hepatic function participants to mild hepatic impairment participants, received a single dose of fenofibrate 48 mg (1 × 48 mg tablet) orally on Day 1. |
| Measure Participants | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
| Firsocostat |
0.20
(0.114)
|
0.10
(0.042)
|
0.26
(0.359)
|
0.10
(0.047)
|
0.23
(0.204)
|
0.08
(0.017)
|
||
| GS-834773 |
0.11
(0.051)
|
0.12
(0.070)
|
0.18
(0.104)
|
0.11
(0.077)
|
0.22
(0.185)
|
0.07
(0.027)
|
||
| Fenofibric Acid |
133.04
(51.253)
|
90.71
(33.405)
|
| Title | PK Parameter: Tlast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) |
|---|---|
| Description | 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). |
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the PK Analysis Sets were analyzed. 6 participants with normal hepatic function served as matched controls across both Cohort 1 and 2. |
| Arm/Group Title | 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 (Severe Hepatic Impairment): Firsocostat 5 mg | Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg | Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg | Cohort 4 (Normal Hepatic Function): Fenofibrate 48 mg |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with mild hepatic impairment received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Matched normal hepatic function participants to mild hepatic impairment participants, received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Participants with moderate hepatic impairment received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Matched normal hepatic function participants to moderate hepatic impairment participants, received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Participants with severe hepatic impairment received a single dose of firsocostat 5 mg (1 × 5 mg capsule) orally on Day 1. | Matched normal hepatic function participants to severe hepatic impairment participants, received a single dose of firsocostat 5 mg (1 × 5 mg capsule) orally on Day 1. | Participants with mild hepatic impairment received a single dose of fenofibrate 48 mg (1 × 48 mg tablet) orally on Day 1. | Matched normal hepatic function participants to mild hepatic impairment participants, received a single dose of fenofibrate 48 mg (1 × 48 mg tablet) orally on Day 1. |
| Measure Participants | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
| Firsocostat |
24.00
|
24.00
|
72.00
|
24.00
|
48.00
|
16.00
|
||
| GS-834773 |
24.00
|
12.00
|
48.02
|
11.00
|
36.04
|
7.00
|
||
| Fenofibric Acid |
96.00
|
84.25
|
| Title | PK Parameter: λz of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) |
|---|---|
| Description | 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). |
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the PK Analysis Sets were analyzed. 6 participants with normal hepatic function served as matched controls across both Cohort 1 and 2. |
| Arm/Group Title | 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 (Severe Hepatic Impairment): Firsocostat 5 mg | Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg | Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg | Cohort 4 (Normal Hepatic Function): Fenofibrate 48 mg |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with mild hepatic impairment received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Matched normal hepatic function participants to mild hepatic impairment participants, received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Participants with moderate hepatic impairment received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Matched normal hepatic function participants to moderate hepatic impairment participants, received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Participants with severe hepatic impairment received a single dose of firsocostat 5 mg (1 × 5 mg capsule) orally on Day 1. | Matched normal hepatic function participants to severe hepatic impairment participants, received a single dose of firsocostat 5 mg (1 × 5 mg capsule) orally on Day 1. | Participants with mild hepatic impairment received a single dose of fenofibrate 48 mg (1 × 48 mg tablet) orally on Day 1. | Matched normal hepatic function participants to mild hepatic impairment participants, received a single dose of fenofibrate 48 mg (1 × 48 mg tablet) orally on Day 1. |
| Measure Participants | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
| Firsocostat |
0.132
(0.1093)
|
0.155
(0.0684)
|
0.096
(0.0753)
|
0.136
(0.0796)
|
0.077
(0.0204)
|
0.193
(0.0765)
|
||
| GS-834773 |
0.133
(0.0948)
|
0.214
(0.0942)
|
0.105
(0.0916)
|
0.209
(0.0918)
|
0.103
(0.0543)
|
0.300
(0.1379)
|
||
| Fenofibric Acid |
0.034
(0.0080)
|
0.038
(0.0082)
|
| Title | PK Parameter: CL/F of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) |
|---|---|
| Description | 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). |
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the PK Analysis Sets were analyzed. 6 participants with normal hepatic function served as matched controls across both Cohort 1 and 2. |
| Arm/Group Title | 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 (Severe Hepatic Impairment): Firsocostat 5 mg | Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg | Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg | Cohort 4 (Normal Hepatic Function): Fenofibrate 48 mg |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with mild hepatic impairment received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Matched normal hepatic function participants to mild hepatic impairment participants, received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Participants with moderate hepatic impairment received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Matched normal hepatic function participants to moderate hepatic impairment participants, received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Participants with severe hepatic impairment received a single dose of firsocostat 5 mg (1 × 5 mg capsule) orally on Day 1. | Matched normal hepatic function participants to severe hepatic impairment participants, received a single dose of firsocostat 5 mg (1 × 5 mg capsule) orally on Day 1. | Participants with mild hepatic impairment received a single dose of fenofibrate 48 mg (1 × 48 mg tablet) orally on Day 1. | Matched normal hepatic function participants to mild hepatic impairment participants, received a single dose of fenofibrate 48 mg (1 × 48 mg tablet) orally on Day 1. |
| Measure Participants | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
| Firsocostat |
259318.9
(239527.46)
|
376896.2
(228676.47)
|
59482.2
(63193.83)
|
395572.3
(226508.90)
|
16969.7
(5154.88)
|
509793.4
(168681.93)
|
||
| GS-834773 |
1467352.6
(1790413.18)
|
3966285.6
(2982349.95)
|
239748.5
(351882.41)
|
4795605.6
(2952570.14)
|
44379.6
(38793.78)
|
4656562.3
(2689827.70)
|
||
| Fenofibric Acid |
909.4
(539.09)
|
1060.8
(391.86)
|
| Title | PK Parameter: Vz/F of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) |
|---|---|
| Description | 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). |
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the PK Analysis Sets were analyzed. 6 participants with normal hepatic function served as matched controls across both Cohort 1 and 2. |
| Arm/Group Title | 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 (Severe Hepatic Impairment): Firsocostat 5 mg | Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg | Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg | Cohort 4 (Normal Hepatic Function): Fenofibrate 48 mg |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with mild hepatic impairment received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Matched normal hepatic function participants to mild hepatic impairment participants, received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Participants with moderate hepatic impairment received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Matched normal hepatic function participants to moderate hepatic impairment participants, received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Participants with severe hepatic impairment received a single dose of firsocostat 5 mg (1 × 5 mg capsule) orally on Day 1. | Matched normal hepatic function participants to severe hepatic impairment participants, received a single dose of firsocostat 5 mg (1 × 5 mg capsule) orally on Day 1. | Participants with mild hepatic impairment received a single dose of fenofibrate 48 mg (1 × 48 mg tablet) orally on Day 1. | Matched normal hepatic function participants to mild hepatic impairment participants, received a single dose of fenofibrate 48 mg (1 × 48 mg tablet) orally on Day 1. |
| Measure Participants | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
| Firsocostat |
2896998.5
(2176020.23)
|
2846198.8
(2249997.50)
|
592810.8
(318935.52)
|
3797739.4
(2684509.46)
|
230242.5
(92293.34)
|
3079474.8
(1593778.35)
|
||
| GS-834773 |
15576712.2
(19451521.66)
|
19236747.1
(10816737.06)
|
2126366.5
(2117217.85)
|
23635388.6
(10179635.17)
|
501512.3
(524040.62)
|
20312673.6
(18230756.23)
|
||
| Fenofibric Acid |
25908.5
(9331.48)
|
28290.3
(8476.01)
|
| Title | PK Parameter: t1/2 of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) |
|---|---|
| Description | 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). |
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the PK Analysis Sets were analyzed. 6 participants with normal hepatic function served as matched controls across both Cohort 1 and 2. |
| Arm/Group Title | 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 (Severe Hepatic Impairment): Firsocostat 5 mg | Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg | Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg | Cohort 4 (Normal Hepatic Function): Fenofibrate 48 mg |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with mild hepatic impairment received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Matched normal hepatic function participants to mild hepatic impairment participants, received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Participants with mild hepatic impairment received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Matched normal hepatic function participants to moderate hepatic impairment participants, received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Participants with severe hepatic impairment received a single dose of firsocostat 5 mg (1 × 5 mg capsule) orally on Day 1. | Matched normal hepatic function participants to severe hepatic impairment participants, received a single dose of firsocostat 5 mg (1 × 5 mg capsule) orally on Day 1. | Participants with mild hepatic impairment received a single dose of fenofibrate 48 mg (1 × 48 mg tablet) orally on Day 1. | Matched normal hepatic function participants to mild hepatic impairment participants, received a single dose of fenofibrate 48 mg (1 × 48 mg tablet) orally on Day 1. |
| Measure Participants | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
| Firsocostat |
5.23
|
4.39
|
11.20
|
5.04
|
9.54
|
3.93
|
||
| GS-834773 |
5.24
|
3.32
|
12.82
|
3.28
|
8.51
|
2.49
|
||
| Fenofibric Acid |
21.33
|
18.27
|
| Title | Percentage of Participants Experiencing Treatment-Emergent Adverse Events (AEs) |
|---|---|
| Description | 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. |
| Time Frame | First dose date plus 30 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set were analyzed. 6 participants served as matched control across both Cohort 1 and 2. |
| Arm/Group Title | Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg | Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg | Cohort 1 & 2 (Normal Hepatic Function): Firsocostat 20 mg | Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg | Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg | Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg | Cohort 4 (Normal Hepatic Function): Fenofibrate 48 mg |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with mild hepatic impairment received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Participants with moderate hepatic impairment received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Matched normal hepatic function participants to mild or moderate hepatic impairment participants received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1 | Participants with severe hepatic impairment received a single dose of firsocostat 5 mg (1 × 5 mg capsule) orally on Day 1. | Matched normal hepatic function participants to severe hepatic impairment participants received a single dose of firsocostat 5 mg (1 × 5 mg capsule) orally on Day 1. | Participants with mild hepatic impairment received a single dose of fenofibrate 48 mg (1 × 48 mg tablet) orally on Day 1. | Matched normal hepatic function participants to mild hepatic impairment participants, received a single dose of fenofibrate 48 mg (1 × 48 mg tablet) orally on Day 1. |
| Measure Participants | 10 | 10 | 14 | 10 | 10 | 10 | 10 |
| Number [percentage of participants] |
20.0
200%
|
10.0
100%
|
7.1
50.7%
|
30.0
300%
|
10.0
100%
|
0
0%
|
10.0
100%
|
| Title | Percentage of Participants Experiencing Laboratory Abnormalities |
|---|---|
| Description | 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. |
| Time Frame | First dose date plus 30 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set were analyzed. 6 participants served as matched control across both Cohort 1 and 2. |
| Arm/Group Title | Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg | Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg | Cohort 1 & 2 (Normal Hepatic Function): Firsocostat 20 mg | Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg | Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg | Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg | Cohort 4 (Normal Hepatic Function): Fenofibrate 48 mg |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with mild hepatic impairment received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Participants with moderate hepatic impairment received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Matched normal hepatic function participants to mild or moderate hepatic impairment participants received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Participants with severe hepatic impairment received a single dose of firsocostat 5 mg (1 × 5 mg capsule) orally on Day 1. | Matched normal hepatic function participants to severe hepatic impairment participants received a single dose of firsocostat 5 mg (1 × 5 mg capsule) orally on Day 1. | Participants with mild hepatic impairment received a single dose of fenofibrate 48 mg (1 × 48 mg tablet) orally on Day 1. | Matched normal hepatic function participants to mild hepatic impairment participants, received a single dose of fenofibrate 48 mg (1 × 48 mg tablet) orally on Day 1. |
| Measure Participants | 10 | 10 | 14 | 10 | 10 | 10 | 10 |
| Number [Percentage of participants] |
100.0
1000%
|
90.0
900%
|
50.0
357.1%
|
100.0
1000%
|
50.0
500%
|
90.0
900%
|
60.0
600%
|
Adverse Events
| Time Frame | First dose date plus 30 days | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Participants in the Safety Analysis Set were analyzed. 6 participants served as matched control across both Cohort 1 and 2. | |||||||||||||
| Arm/Group Title | Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg | Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg | Cohort 1 & 2 (Normal Hepatic Function): Firsocostat 20 mg | Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg | Cohort 3 (Normal Hepatic Function) Firsocostat 5 mg | Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg | Cohort 4 (Normal Hepatic Function) Fenofibrate 48 mg | |||||||
| Arm/Group Description | Participants with mild hepatic impairment received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Participants with moderate hepatic impairment received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | Matched normal hepatic function participants to mild or moderate hepatic impairment participants received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1 | Participants with severe hepatic impairment received a single dose of firsocostat 5 mg (1 × 5 mg capsule) orally on Day 1. | Matched normal hepatic function participants to severe hepatic impairment participants received a single dose of firsocostat 5 mg (1 × 5 mg capsule) orally on Day 1. | Participants with mild hepatic impairment received a single dose of fenofibrate 48 mg (1 × 48 mg tablet) orally on Day 1. | Matched normal hepatic function participants to mild hepatic impairment participants, received a single dose of fenofibrate 48 mg (1 × 48 mg tablet) orally on Day 1. | |||||||
All Cause Mortality |
||||||||||||||
| Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg | Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg | Cohort 1 & 2 (Normal Hepatic Function): Firsocostat 20 mg | Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg | Cohort 3 (Normal Hepatic Function) Firsocostat 5 mg | Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg | Cohort 4 (Normal Hepatic Function) Fenofibrate 48 mg | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/10 (0%) | 0/10 (0%) | 0/14 (0%) | 0/10 (0%) | 0/10 (0%) | 0/10 (0%) | 0/10 (0%) | |||||||
Serious Adverse Events |
||||||||||||||
| Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg | Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg | Cohort 1 & 2 (Normal Hepatic Function): Firsocostat 20 mg | Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg | Cohort 3 (Normal Hepatic Function) Firsocostat 5 mg | Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg | Cohort 4 (Normal Hepatic Function) Fenofibrate 48 mg | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/10 (0%) | 0/10 (0%) | 0/14 (0%) | 0/10 (0%) | 0/10 (0%) | 0/10 (0%) | 0/10 (0%) | |||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||
| Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg | Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg | Cohort 1 & 2 (Normal Hepatic Function): Firsocostat 20 mg | Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg | Cohort 3 (Normal Hepatic Function) Firsocostat 5 mg | Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg | Cohort 4 (Normal Hepatic Function) Fenofibrate 48 mg | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/10 (20%) | 1/10 (10%) | 1/14 (7.1%) | 3/10 (30%) | 1/10 (10%) | 0/10 (0%) | 1/10 (10%) | |||||||
| Gastrointestinal disorders | ||||||||||||||
| Diarrhoea | 0/10 (0%) | 0/10 (0%) | 0/14 (0%) | 1/10 (10%) | 0/10 (0%) | 0/10 (0%) | 1/10 (10%) | |||||||
| Toothache | 0/10 (0%) | 0/10 (0%) | 0/14 (0%) | 1/10 (10%) | 0/10 (0%) | 0/10 (0%) | 0/10 (0%) | |||||||
| Infections and infestations | ||||||||||||||
| Herpes simplex | 0/10 (0%) | 0/10 (0%) | 1/14 (7.1%) | 0/10 (0%) | 0/10 (0%) | 0/10 (0%) | 0/10 (0%) | |||||||
| Investigations | ||||||||||||||
| Amylase increased | 0/10 (0%) | 0/10 (0%) | 0/14 (0%) | 0/10 (0%) | 1/10 (10%) | 0/10 (0%) | 0/10 (0%) | |||||||
| Nervous system disorders | ||||||||||||||
| Headache | 1/10 (10%) | 1/10 (10%) | 1/14 (7.1%) | 0/10 (0%) | 0/10 (0%) | 0/10 (0%) | 0/10 (0%) | |||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||
| Skin exfoliation | 0/10 (0%) | 0/10 (0%) | 0/14 (0%) | 1/10 (10%) | 0/10 (0%) | 0/10 (0%) | 0/10 (0%) | |||||||
| Vascular disorders | ||||||||||||||
| Flushing | 1/10 (10%) | 0/10 (0%) | 0/14 (0%) | 0/10 (0%) | 0/10 (0%) | 0/10 (0%) | 0/10 (0%) | |||||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or The study has been completed at all study sites for at least 2 years
Results Point of Contact
| Name/Title | Gilead Clinical Study Information Center |
|---|---|
| Organization | Gilead Sciences |
| Phone | 1-833-445-3230 (GILEAD-0) |
| GileadClinicalTrials@gilead.com |
Responsible Party:
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT02891408
Other Study ID Numbers:
- GS-US-426-3988
First Posted:
Sep 7, 2016
Last Update Posted:
Dec 17, 2020
Last Verified:
Nov 1, 2020