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Pharmacokinetics of Firsocostat or Fenofibrate in Adults With Normal and Impaired Hepatic Function (HI)

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ClinicalTrials.gov Identifier: NCT02891408
Recruitment Status : Completed
First Posted : September 7, 2016
Last Update Posted : May 20, 2019
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

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 subjects with normal hepatic function and mild hepatic impairment.

Condition or disease Intervention/treatment Phase
Nonalcoholic Steatohepatitis (NASH) Drug: Firsocostat Drug: Fenofibrate Phase 1

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Study Type : Interventional  (Clinical Trial)
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 : September 23, 2016
Actual Primary Completion Date : May 5, 2019
Actual Study Completion Date : May 13, 2019


Arm Intervention/treatment
Experimental: Cohort 1 (Mild Hepatic Impairment)
Participants with mild hepatic impairment and matched healthy controls will receive a single dose of 20 mg (2 x 10 mg) firsocostat capsule (s).
Drug: Firsocostat
Tablet(s) or Capsule(s) administered orally on Day 1
Other Name: GS-0976

Experimental: Cohort 2 (Moderate Hepatic Impairment)
Participants with moderate hepatic impairment and matched healthy controls will receive a single dose of 20 mg (2 x 10 mg) firsocostat capsule (s).
Drug: Firsocostat
Tablet(s) or Capsule(s) administered orally on Day 1
Other Name: GS-0976

Experimental: Cohort 3 (Severe Hepatic Impairment)
Based on the cumulative review of safety and PK data from Cohorts 1 and 2, Cohort 3 may or may not be initiated at the discretion of the investigator and Sponsor. If Cohort 3 is initiated, participants with severe hepatic impairment and matched healthy controls will receive a single dose of 5 mg (1 x 5 mg) firsocostat tablet (s).
Drug: Firsocostat
Tablet(s) or Capsule(s) administered orally on Day 1
Other Name: GS-0976

Experimental: Cohort 4 (Mild Hepatic Impairment)
Participants with mild hepatic impairment and matched healthy controls will receive a single dose of 48 mg (1 x 48 mg) fenofibrate tablet (s).
Drug: Fenofibrate
Tablet(s) administered orally on Day 1




Primary Outcome Measures :
  1. PK Parameter: AUClast of firsocostat or fenofibrate (and their metabolites, as applicable) [ Time Frame: Predose and up to 96 hours postdose ]
    AUClast is defined as the concentration of drug from time zero to the last observable concentration.

  2. PK Parameter: AUCinf of firsocostat or fenofibrate (and their metabolites, as applicable) [ Time Frame: Predose and up to 96 hours postdose ]
    AUCinf is defined as the concentration of drug extrapolated to infinite time.

  3. PK Parameter: Cmax of firsocostat or fenofibrate (and their metabolites, as applicable) [ Time Frame: Predose and up to 96 hours postdose ]
    Cmax is defined as the maximum observed concentration of drug.

  4. PK Parameter: %AUCexp of firsocostat or fenofibrate (and their metabolites, as applicable) [ Time Frame: Predose and up to 96 hours postdose ]
    %AUCexp is defined as the percentage of AUC extrapolated between AUClast and AUCinf.

  5. PK Parameter: Tmax of firsocostat or fenofibrate (and their metabolites, as applicable) [ Time Frame: Predose and up to 96 hours postdose ]
    Tmax is defined as the time (observed time point) of Cmax.

  6. PK Parameter: Clast of firsocostat or fenofibrate (and their metabolites, as applicable) [ Time Frame: Predose and up to 96 hours postdose ]
    Clast is defined as the last observable concentration of drug.

  7. PK Parameter: Tlast of firsocostat or fenofibrate (and their metabolites, as applicable) [ Time Frame: Predose and up to 96 hours postdose ]
    Tlast is defined as the time (observed time point) of Clast.

  8. PK Parameter: λz of firsocostat or fenofibrate (and their metabolites, as applicable) [ Time Frame: Predose and up to 96 hours postdose ]
    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.

  9. PK Parameter: CL/F of firsocostat or fenofibrate (and their metabolites, as applicable) [ Time Frame: Predose and up to 96 hours postdose ]
    CL/F is defined as the apparent oral clearance following administration of the drug.

  10. PK Parameter: Vz/F of firsocostat or fenofibrate (and their metabolites, as applicable) [ Time Frame: Predose and up to 96 hours postdose ]
    Vz/F is defined as the apparent volume of distribution of the drug.

  11. PK Parameter: t1/2 of firsocostat or fenofibrate (and their metabolites, as applicable) [ Time Frame: Predose and up to 96 hours postdose ]
    t1/2 is defined as the estimate of the terminal elimination half-life of the drug.


Secondary Outcome Measures :
  1. Incidence of adverse events [ Time Frame: Up to 31 days ]
  2. Incidence of laboratory abnormalities [ Time Frame: Up to 31 days ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Key Inclusion Criteria:

Cohort 1 (Mild Hepatic Impairment):

  • Male and non-pregnant/non-lactating females, ages 18-70 years inclusive 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, ages 18-70 years inclusive 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, ages 18-70 years inclusive 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, ages 18-70 years inclusive 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).

NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02891408


Locations
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United States, California
Tustin, California, United States
United States, Florida
Miami, Florida, United States
Orlando, Florida, United States
United States, Minnesota
Minneapolis, Minnesota, United States
United States, Texas
San Antonio, Texas, United States
Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Gilead Study Director Gilead Sciences

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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02891408     History of Changes
Other Study ID Numbers: GS-US-426-3988
First Posted: September 7, 2016    Key Record Dates
Last Update Posted: May 20, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Fatty Liver
Non-alcoholic Fatty Liver Disease
Liver Diseases
Digestive System Diseases
Fenofibrate
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents