Nonalcoholic Steatohepatitis (NASH)
Conditions
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.
Interventions
DRUGFirsocostat
Capsule(s) administered orally on Day 1
DRUGFenofibrate
Tablet administered orally on Day 1
Sponsors
Gilead Sciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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). |
| 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Countries
United States
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg Participants with mild hepatic impairment received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | 10 |
| Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg Participants with moderate hepatic impairment received a single dose of firsocostat 20 mg (2 × 10 mg capsules) orally on Day 1. | 10 |
| Cohort 1 & 2 (Normal Hepatic Function): Firsocostat 20 mg 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 | 14 |
| Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg Participants with severe hepatic impairment received a single dose of firsocostat 5 mg (1 × 5 mg capsule) orally on Day 1. | 10 |
| Cohort 3 (Normal Hepatic Function) Firsocostat 5 mg 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. | 10 |
| Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg Participants with mild hepatic impairment received a single dose of fenofibrate 48 mg (1 × 48 mg tablet) orally on Day 1. | 10 |
| Cohort 4 (Normal Hepatic Function) Fenofibrate 48 mg 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. | 10 |
| Total | 74 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg | Total | Cohort 4 (Normal Hepatic Function) Fenofibrate 48 mg | 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 |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 58 years STANDARD_DEVIATION 6.4 | 55 years STANDARD_DEVIATION 8 | 58 years STANDARD_DEVIATION 5.1 | 55 years STANDARD_DEVIATION 8.1 | 56 years STANDARD_DEVIATION 9.1 | 55 years STANDARD_DEVIATION 8 | 53 years STANDARD_DEVIATION 10.8 | 54 years STANDARD_DEVIATION 8.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 40 Participants | 6 Participants | 3 Participants | 6 Participants | 7 Participants | 6 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 34 Participants | 4 Participants | 7 Participants | 4 Participants | 7 Participants | 4 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 14 Participants | 2 Participants | 4 Participants | 0 Participants | 4 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 57 Participants | 8 Participants | 5 Participants | 9 Participants | 9 Participants | 9 Participants | 9 Participants |
| Sex: Female, Male Female | 3 Participants | 22 Participants | 3 Participants | 2 Participants | 3 Participants | 3 Participants | 4 Participants | 4 Participants |
| Sex: Female, Male Male | 7 Participants | 52 Participants | 7 Participants | 8 Participants | 7 Participants | 11 Participants | 6 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 | 0 / 14 | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 2 / 10 | 1 / 10 | 1 / 14 | 3 / 10 | 1 / 10 | 0 / 10 | 1 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 | 0 / 14 | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 10 |
Outcome results
Primary
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).
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)
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg | Pharmacokinetic (PK) Parameter: AUClast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 160.6 hr*ng/mL | Standard Deviation 158.28 |
| Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg | Pharmacokinetic (PK) Parameter: AUClast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 46.2 hr*ng/mL | Standard Deviation 57.67 |
| Cohort 1 (Normal Hepatic Function): Firsocostat 20 mg | Pharmacokinetic (PK) Parameter: AUClast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 7.4 hr*ng/mL | Standard Deviation 5.83 |
| Cohort 1 (Normal Hepatic Function): Firsocostat 20 mg | Pharmacokinetic (PK) Parameter: AUClast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 69.8 hr*ng/mL | Standard Deviation 38.73 |
| Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg | Pharmacokinetic (PK) Parameter: AUClast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 395.8 hr*ng/mL | Standard Deviation 535.93 |
| Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg | Pharmacokinetic (PK) Parameter: AUClast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 682.1 hr*ng/mL | Standard Deviation 497.09 |
| Cohort 2 (Normal Hepatic Function): Firsocostat 20 mg | Pharmacokinetic (PK) Parameter: AUClast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 5.1 hr*ng/mL | Standard Deviation 3.21 |
| Cohort 2 (Normal Hepatic Function): Firsocostat 20 mg | Pharmacokinetic (PK) Parameter: AUClast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 64.5 hr*ng/mL | Standard Deviation 33.22 |
| Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg | Pharmacokinetic (PK) Parameter: AUClast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 310.4 hr*ng/mL | Standard Deviation 75.18 |
| Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg | Pharmacokinetic (PK) Parameter: AUClast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 153.3 hr*ng/mL | Standard Deviation 65.72 |
| Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg | Pharmacokinetic (PK) Parameter: AUClast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 1.4 hr*ng/mL | Standard Deviation 1.38 |
| Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg | Pharmacokinetic (PK) Parameter: AUClast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 10.2 hr*ng/mL | Standard Deviation 2.92 |
| Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg | Pharmacokinetic (PK) Parameter: AUClast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Fenofibric Acid | 61207.4 hr*ng/mL | Standard Deviation 24630.23 |
| Cohort 4 (Normal Hepatic Function): Fenofibrate 48 mg | Pharmacokinetic (PK) Parameter: AUClast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Fenofibric Acid | 48128.0 hr*ng/mL | Standard Deviation 17377.69 |
Comparison: AUClast of Firsocostat90% CI: [98, 332]
Comparison: AUClast of Firsocostat90% CI: [488, 1589]
Comparison: AUClast of Firsocostat90% CI: [2446, 3881]
Comparison: AUClast of GS-83477390% CI: [185, 998]
Comparison: AUClast of GS-83477390% CI: [1867, 10449]
Comparison: AUClast of GS-83477390% CI: [7932, 27153]
Comparison: AUClast of Fenofibric Acid90% CI: [86, 173]
Primary
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).
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)
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg | PK Parameter: % AUCexp of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 7.16 percentage of AUC | Standard Deviation 7.997 |
| Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg | PK Parameter: % AUCexp of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 2.54 percentage of AUC | Standard Deviation 2.378 |
| Cohort 1 (Normal Hepatic Function): Firsocostat 20 mg | PK Parameter: % AUCexp of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 13.16 percentage of AUC | Standard Deviation 12.642 |
| Cohort 1 (Normal Hepatic Function): Firsocostat 20 mg | PK Parameter: % AUCexp of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 1.36 percentage of AUC | Standard Deviation 1.222 |
| Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg | PK Parameter: % AUCexp of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 0.63 percentage of AUC | Standard Deviation 0.788 |
| Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg | PK Parameter: % AUCexp of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 1.71 percentage of AUC | Standard Deviation 1.889 |
| Cohort 2 (Normal Hepatic Function): Firsocostat 20 mg | PK Parameter: % AUCexp of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 13.59 percentage of AUC | Standard Deviation 12.288 |
| Cohort 2 (Normal Hepatic Function): Firsocostat 20 mg | PK Parameter: % AUCexp of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 1.92 percentage of AUC | Standard Deviation 1.645 |
| Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg | PK Parameter: % AUCexp of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 1.35 percentage of AUC | Standard Deviation 1.953 |
| Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg | PK Parameter: % AUCexp of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 2.21 percentage of AUC | Standard Deviation 2.288 |
| Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg | PK Parameter: % AUCexp of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 4.68 percentage of AUC | Standard Deviation 2.671 |
| Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg | PK Parameter: % AUCexp of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 25.94 percentage of AUC | Standard Deviation 19.497 |
| Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg | PK Parameter: % AUCexp of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Fenofibric Acid | 7.11 percentage of AUC | Standard Deviation 3.767 |
| Cohort 4 (Normal Hepatic Function): Fenofibrate 48 mg | PK Parameter: % AUCexp of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Fenofibric Acid | 5.38 percentage of AUC | Standard Deviation 2.758 |
Primary
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).
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)
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg | PK Parameter: AUCinf of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 165.2 hr*ng/mL | Standard Deviation 162.71 |
| Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg | PK Parameter: AUCinf of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 48.5 hr*ng/mL | Standard Deviation 59.21 |
| Cohort 1 (Normal Hepatic Function): Firsocostat 20 mg | PK Parameter: AUCinf of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 8.2 hr*ng/mL | Standard Deviation 5.84 |
| Cohort 1 (Normal Hepatic Function): Firsocostat 20 mg | PK Parameter: AUCinf of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 70.5 hr*ng/mL | Standard Deviation 38.82 |
| Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg | PK Parameter: AUCinf of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 399.0 hr*ng/mL | Standard Deviation 537.09 |
| Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg | PK Parameter: AUCinf of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 686.6 hr*ng/mL | Standard Deviation 499.35 |
| Cohort 2 (Normal Hepatic Function): Firsocostat 20 mg | PK Parameter: AUCinf of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 5.9 hr*ng/mL | Standard Deviation 3.46 |
| Cohort 2 (Normal Hepatic Function): Firsocostat 20 mg | PK Parameter: AUCinf of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 65.8 hr*ng/mL | Standard Deviation 34.36 |
| Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg | PK Parameter: AUCinf of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 313.6 hr*ng/mL | Standard Deviation 72.68 |
| Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg | PK Parameter: AUCinf of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 155.9 hr*ng/mL | Standard Deviation 65.85 |
| Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg | PK Parameter: AUCinf of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 1.6 hr*ng/mL | Standard Deviation 1.37 |
| Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg | PK Parameter: AUCinf of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 10.6 hr*ng/mL | Standard Deviation 2.97 |
| Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg | PK Parameter: AUCinf of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Fenofibric Acid | 65530.7 hr*ng/mL | Standard Deviation 25917.76 |
| Cohort 4 (Normal Hepatic Function): Fenofibrate 48 mg | PK Parameter: AUCinf of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Fenofibric Acid | 50754.1 hr*ng/mL | Standard Deviation 18262.73 |
Comparison: AUCinf of GS-83477390% CI: [179, 892]
Comparison: AUCinf of GS-83477390% CI: [1641, 9000]
Comparison: AUCinf of Firsocostat90% CI: [100, 337]
Comparison: AUCinf of Firsocostat90% CI: [482, 1568]
Comparison: AUCinf of Firsocostat90% CI: [2389, 3708]
Comparison: AUCinf of GS-83477390% CI: [6525, 17585]
Comparison: AUCinf of Fenofibric Acid90% CI: [89, 174]
Primary
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).
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)
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg | PK Parameter: Clast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 0.20 ng/mL | Standard Deviation 0.114 |
| Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg | PK Parameter: Clast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 0.11 ng/mL | Standard Deviation 0.051 |
| Cohort 1 (Normal Hepatic Function): Firsocostat 20 mg | PK Parameter: Clast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 0.12 ng/mL | Standard Deviation 0.07 |
| Cohort 1 (Normal Hepatic Function): Firsocostat 20 mg | PK Parameter: Clast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 0.10 ng/mL | Standard Deviation 0.042 |
| Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg | PK Parameter: Clast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 0.18 ng/mL | Standard Deviation 0.104 |
| Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg | PK Parameter: Clast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 0.26 ng/mL | Standard Deviation 0.359 |
| Cohort 2 (Normal Hepatic Function): Firsocostat 20 mg | PK Parameter: Clast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 0.11 ng/mL | Standard Deviation 0.077 |
| Cohort 2 (Normal Hepatic Function): Firsocostat 20 mg | PK Parameter: Clast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 0.10 ng/mL | Standard Deviation 0.047 |
| Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg | PK Parameter: Clast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 0.23 ng/mL | Standard Deviation 0.204 |
| Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg | PK Parameter: Clast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 0.22 ng/mL | Standard Deviation 0.185 |
| Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg | PK Parameter: Clast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 0.07 ng/mL | Standard Deviation 0.027 |
| Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg | PK Parameter: Clast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 0.08 ng/mL | Standard Deviation 0.017 |
| Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg | PK Parameter: Clast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Fenofibric Acid | 133.04 ng/mL | Standard Deviation 51.253 |
| Cohort 4 (Normal Hepatic Function): Fenofibrate 48 mg | PK Parameter: Clast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Fenofibric Acid | 90.71 ng/mL | Standard Deviation 33.405 |
Primary
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).
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)
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg | PK Parameter: CL/F of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 259318.9 mL/hour | Standard Deviation 239527.46 |
| Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg | PK Parameter: CL/F of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 1467352.6 mL/hour | Standard Deviation 1790413.18 |
| Cohort 1 (Normal Hepatic Function): Firsocostat 20 mg | PK Parameter: CL/F of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 3966285.6 mL/hour | Standard Deviation 2982349.95 |
| Cohort 1 (Normal Hepatic Function): Firsocostat 20 mg | PK Parameter: CL/F of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 376896.2 mL/hour | Standard Deviation 228676.47 |
| Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg | PK Parameter: CL/F of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 239748.5 mL/hour | Standard Deviation 351882.41 |
| Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg | PK Parameter: CL/F of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 59482.2 mL/hour | Standard Deviation 63193.83 |
| Cohort 2 (Normal Hepatic Function): Firsocostat 20 mg | PK Parameter: CL/F of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 4795605.6 mL/hour | Standard Deviation 2952570.14 |
| Cohort 2 (Normal Hepatic Function): Firsocostat 20 mg | PK Parameter: CL/F of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 395572.3 mL/hour | Standard Deviation 226508.9 |
| Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg | PK Parameter: CL/F of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 16969.7 mL/hour | Standard Deviation 5154.88 |
| Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg | PK Parameter: CL/F of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 44379.6 mL/hour | Standard Deviation 38793.78 |
| Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg | PK Parameter: CL/F of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 4656562.3 mL/hour | Standard Deviation 2689827.7 |
| Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg | PK Parameter: CL/F of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 509793.4 mL/hour | Standard Deviation 168681.93 |
| Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg | PK Parameter: CL/F of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Fenofibric Acid | 909.4 mL/hour | Standard Deviation 539.09 |
| Cohort 4 (Normal Hepatic Function): Fenofibrate 48 mg | PK Parameter: CL/F of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Fenofibric Acid | 1060.8 mL/hour | Standard Deviation 391.86 |
Primary
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).
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)
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg | PK Parameter: Cmax of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 50.9 ng/mL | Standard Deviation 45.96 |
| Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg | PK Parameter: Cmax of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 12.9 ng/mL | Standard Deviation 16.08 |
| Cohort 1 (Normal Hepatic Function): Firsocostat 20 mg | PK Parameter: Cmax of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 2.3 ng/mL | Standard Deviation 2.11 |
| Cohort 1 (Normal Hepatic Function): Firsocostat 20 mg | PK Parameter: Cmax of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 25.4 ng/mL | Standard Deviation 20.44 |
| Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg | PK Parameter: Cmax of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 77.3 ng/mL | Standard Deviation 56.03 |
| Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg | PK Parameter: Cmax of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 197.7 ng/mL | Standard Deviation 118.67 |
| Cohort 2 (Normal Hepatic Function): Firsocostat 20 mg | PK Parameter: Cmax of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 1.4 ng/mL | Standard Deviation 1.16 |
| Cohort 2 (Normal Hepatic Function): Firsocostat 20 mg | PK Parameter: Cmax of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 20.1 ng/mL | Standard Deviation 12.09 |
| Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg | PK Parameter: Cmax of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 73.8 ng/mL | Standard Deviation 17.7 |
| Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg | PK Parameter: Cmax of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 31.3 ng/mL | Standard Deviation 14.66 |
| Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg | PK Parameter: Cmax of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 0.5 ng/mL | Standard Deviation 0.64 |
| Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg | PK Parameter: Cmax of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 3.0 ng/mL | Standard Deviation 1.56 |
| Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg | PK Parameter: Cmax of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Fenofibric Acid | 2723.0 ng/mL | Standard Deviation 1078.36 |
| Cohort 4 (Normal Hepatic Function): Fenofibrate 48 mg | PK Parameter: Cmax of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Fenofibric Acid | 2451.0 ng/mL | Standard Deviation 808.68 |
Comparison: Cmax of Firsocostat90% CI: [87, 326]
Comparison: Cmax of Firsocostat90% CI: [537, 1526]
Comparison: Cmax of Firsocostat90% CI: [1994, 3708]
Comparison: Cmax of GS-83477390% CI: [163, 942]
Comparison: Cmax of GS-83477390% CI: [2170, 9207]
Comparison: Cmax of GS-83477390% CI: [4945, 17407]
Comparison: Cmax of Fenofibric Acid90% CI: [81, 146]
Primary
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).
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)
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg | PK Parameter: t1/2 of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 5.23 hours |
| Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg | PK Parameter: t1/2 of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 5.24 hours |
| Cohort 1 (Normal Hepatic Function): Firsocostat 20 mg | PK Parameter: t1/2 of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 3.32 hours |
| Cohort 1 (Normal Hepatic Function): Firsocostat 20 mg | PK Parameter: t1/2 of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 4.39 hours |
| Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg | PK Parameter: t1/2 of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 12.82 hours |
| Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg | PK Parameter: t1/2 of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 11.20 hours |
| Cohort 2 (Normal Hepatic Function): Firsocostat 20 mg | PK Parameter: t1/2 of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 3.28 hours |
| Cohort 2 (Normal Hepatic Function): Firsocostat 20 mg | PK Parameter: t1/2 of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 5.04 hours |
| Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg | PK Parameter: t1/2 of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 9.54 hours |
| Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg | PK Parameter: t1/2 of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 8.51 hours |
| Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg | PK Parameter: t1/2 of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 2.49 hours |
| Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg | PK Parameter: t1/2 of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 3.93 hours |
| Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg | PK Parameter: t1/2 of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Fenofibric Acid | 21.33 hours |
| Cohort 4 (Normal Hepatic Function): Fenofibrate 48 mg | PK Parameter: t1/2 of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Fenofibric Acid | 18.27 hours |
Primary
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).
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)
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg | PK Parameter: Tlast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 24.00 hours |
| Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg | PK Parameter: Tlast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 24.00 hours |
| Cohort 1 (Normal Hepatic Function): Firsocostat 20 mg | PK Parameter: Tlast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 12.00 hours |
| Cohort 1 (Normal Hepatic Function): Firsocostat 20 mg | PK Parameter: Tlast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 24.00 hours |
| Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg | PK Parameter: Tlast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 48.02 hours |
| Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg | PK Parameter: Tlast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 72.00 hours |
| Cohort 2 (Normal Hepatic Function): Firsocostat 20 mg | PK Parameter: Tlast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 11.00 hours |
| Cohort 2 (Normal Hepatic Function): Firsocostat 20 mg | PK Parameter: Tlast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 24.00 hours |
| Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg | PK Parameter: Tlast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 48.00 hours |
| Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg | PK Parameter: Tlast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 36.04 hours |
| Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg | PK Parameter: Tlast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 7.00 hours |
| Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg | PK Parameter: Tlast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 16.00 hours |
| Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg | PK Parameter: Tlast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Fenofibric Acid | 96.00 hours |
| Cohort 4 (Normal Hepatic Function): Fenofibrate 48 mg | PK Parameter: Tlast of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Fenofibric Acid | 84.25 hours |
Primary
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).
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)
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg | PK Parameter: Tmax of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 1.00 hours |
| Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg | PK Parameter: Tmax of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 1.50 hours |
| Cohort 1 (Normal Hepatic Function): Firsocostat 20 mg | PK Parameter: Tmax of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 1.00 hours |
| Cohort 1 (Normal Hepatic Function): Firsocostat 20 mg | PK Parameter: Tmax of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 1.00 hours |
| Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg | PK Parameter: Tmax of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 1.00 hours |
| Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg | PK Parameter: Tmax of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 1.00 hours |
| Cohort 2 (Normal Hepatic Function): Firsocostat 20 mg | PK Parameter: Tmax of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 1.50 hours |
| Cohort 2 (Normal Hepatic Function): Firsocostat 20 mg | PK Parameter: Tmax of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 1.00 hours |
| Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg | PK Parameter: Tmax of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 1.50 hours |
| Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg | PK Parameter: Tmax of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 2.00 hours |
| Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg | PK Parameter: Tmax of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 2.50 hours |
| Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg | PK Parameter: Tmax of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 2.50 hours |
| Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg | PK Parameter: Tmax of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Fenofibric Acid | 3.00 hours |
| Cohort 4 (Normal Hepatic Function): Fenofibrate 48 mg | PK Parameter: Tmax of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Fenofibric Acid | 2.50 hours |
Primary
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).
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)
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg | PK Parameter: Vz/F of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 2896998.5 mL | Standard Deviation 2176020.23 |
| Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg | PK Parameter: Vz/F of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 15576712.2 mL | Standard Deviation 19451521.66 |
| Cohort 1 (Normal Hepatic Function): Firsocostat 20 mg | PK Parameter: Vz/F of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 19236747.1 mL | Standard Deviation 10816737.06 |
| Cohort 1 (Normal Hepatic Function): Firsocostat 20 mg | PK Parameter: Vz/F of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 2846198.8 mL | Standard Deviation 2249997.5 |
| Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg | PK Parameter: Vz/F of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 2126366.5 mL | Standard Deviation 2117217.85 |
| Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg | PK Parameter: Vz/F of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 592810.8 mL | Standard Deviation 318935.52 |
| Cohort 2 (Normal Hepatic Function): Firsocostat 20 mg | PK Parameter: Vz/F of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 23635388.6 mL | Standard Deviation 10179635.17 |
| Cohort 2 (Normal Hepatic Function): Firsocostat 20 mg | PK Parameter: Vz/F of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 3797739.4 mL | Standard Deviation 2684509.46 |
| Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg | PK Parameter: Vz/F of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 230242.5 mL | Standard Deviation 92293.34 |
| Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg | PK Parameter: Vz/F of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 501512.3 mL | Standard Deviation 524040.62 |
| Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg | PK Parameter: Vz/F of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 20312673.6 mL | Standard Deviation 18230756.23 |
| Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg | PK Parameter: Vz/F of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 3079474.8 mL | Standard Deviation 1593778.35 |
| Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg | PK Parameter: Vz/F of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Fenofibric Acid | 25908.5 mL | Standard Deviation 9331.48 |
| Cohort 4 (Normal Hepatic Function): Fenofibrate 48 mg | PK Parameter: Vz/F of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Fenofibric Acid | 28290.3 mL | Standard Deviation 8476.01 |
Primary
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).
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)
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg | PK Parameter: λz of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 0.132 1/hour | Standard Deviation 0.1093 |
| Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg | PK Parameter: λz of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 0.133 1/hour | Standard Deviation 0.0948 |
| Cohort 1 (Normal Hepatic Function): Firsocostat 20 mg | PK Parameter: λz of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 0.214 1/hour | Standard Deviation 0.0942 |
| Cohort 1 (Normal Hepatic Function): Firsocostat 20 mg | PK Parameter: λz of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 0.155 1/hour | Standard Deviation 0.0684 |
| Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg | PK Parameter: λz of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 0.105 1/hour | Standard Deviation 0.0916 |
| Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg | PK Parameter: λz of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 0.096 1/hour | Standard Deviation 0.0753 |
| Cohort 2 (Normal Hepatic Function): Firsocostat 20 mg | PK Parameter: λz of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 0.209 1/hour | Standard Deviation 0.0918 |
| Cohort 2 (Normal Hepatic Function): Firsocostat 20 mg | PK Parameter: λz of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 0.136 1/hour | Standard Deviation 0.0796 |
| Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg | PK Parameter: λz of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 0.077 1/hour | Standard Deviation 0.0204 |
| Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg | PK Parameter: λz of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 0.103 1/hour | Standard Deviation 0.0543 |
| Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg | PK Parameter: λz of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | GS-834773 | 0.300 1/hour | Standard Deviation 0.1379 |
| Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg | PK Parameter: λz of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Firsocostat | 0.193 1/hour | Standard Deviation 0.0765 |
| Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg | PK Parameter: λz of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Fenofibric Acid | 0.034 1/hour | Standard Deviation 0.008 |
| Cohort 4 (Normal Hepatic Function): Fenofibrate 48 mg | PK Parameter: λz of Firsocostat, GS-834773 (Primary Metabolite of Firsocostat), and Fenofibric Acid (Primary Metabolite of Fenofibrate) | Fenofibric Acid | 0.038 1/hour | Standard Deviation 0.0082 |
Secondary
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.
Time frame: First dose date plus 30 days
Population: Participants in the Safety Analysis Set were analyzed. 6 participants served as matched control across both Cohort 1 and 2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg | Percentage of Participants Experiencing Laboratory Abnormalities | 100.0 Percentage of participants |
| Cohort 1 (Normal Hepatic Function): Firsocostat 20 mg | Percentage of Participants Experiencing Laboratory Abnormalities | 90.0 Percentage of participants |
| Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg | Percentage of Participants Experiencing Laboratory Abnormalities | 50.0 Percentage of participants |
| Cohort 2 (Normal Hepatic Function): Firsocostat 20 mg | Percentage of Participants Experiencing Laboratory Abnormalities | 100.0 Percentage of participants |
| Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg | Percentage of Participants Experiencing Laboratory Abnormalities | 50.0 Percentage of participants |
| Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg | Percentage of Participants Experiencing Laboratory Abnormalities | 90.0 Percentage of participants |
| Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg | Percentage of Participants Experiencing Laboratory Abnormalities | 60.0 Percentage of participants |
Secondary
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.
Time frame: First dose date plus 30 days
Population: Participants in the Safety Analysis Set were analyzed. 6 participants served as matched control across both Cohort 1 and 2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg | Percentage of Participants Experiencing Treatment-Emergent Adverse Events (AEs) | 20.0 percentage of participants |
| Cohort 1 (Normal Hepatic Function): Firsocostat 20 mg | Percentage of Participants Experiencing Treatment-Emergent Adverse Events (AEs) | 10.0 percentage of participants |
| Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg | Percentage of Participants Experiencing Treatment-Emergent Adverse Events (AEs) | 7.1 percentage of participants |
| Cohort 2 (Normal Hepatic Function): Firsocostat 20 mg | Percentage of Participants Experiencing Treatment-Emergent Adverse Events (AEs) | 30.0 percentage of participants |
| Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg | Percentage of Participants Experiencing Treatment-Emergent Adverse Events (AEs) | 10.0 percentage of participants |
| Cohort 3 (Normal Hepatic Function): Firsocostat 5 mg | Percentage of Participants Experiencing Treatment-Emergent Adverse Events (AEs) | 0 percentage of participants |
| Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg | Percentage of Participants Experiencing Treatment-Emergent Adverse Events (AEs) | 10.0 percentage of participants |