Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

Tracking Information
First Submitted Date  ICMJE September 1, 2016
First Posted Date  ICMJE September 7, 2016
Last Update Posted Date May 20, 2019
Actual Study Start Date  ICMJE September 23, 2016
Actual Primary Completion Date May 5, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 23, 2019)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: September 1, 2016)
  • PK Parameter: AUClast of GS-0976 [ 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.
  • PK Parameter: AUCinf of GS-0976 [ Time Frame: Predose and up to 96 hours postdose ]
    AUCinf is defined as the concentration of drug extrapolated to infinite time.
  • PK Parameter: Cmax of GS-0976 [ Time Frame: Predose and up to 96 hours postdose ]
    Cmax is defined as the maximum observed concentration of drug.
  • PK Parameter: %AUCexp of GS-0976 [ Time Frame: Predose and up to 96 hours postdose ]
    %AUCexp is defined as the percentage of AUC extrapolated between AUClast and AUCinf.
  • PK Parameter: Tmax of GS-0976 [ Time Frame: Predose and up to 96 hours postdose ]
    Tmax is defined as the time (observed time point) of Cmax.
  • PK Parameter: Clast of GS-0976 [ Time Frame: Predose and up to 96 hours postdose ]
    Clast is defined as the last observable concentration of drug.
  • PK Parameter: Tlast of GS-0976 [ Time Frame: Predose and up to 96 hours postdose ]
    Tlast is defined as the time (observed time point) of Clast.
  • PK Parameter: λz of GS-0976 [ Time Frame: Predose and up to 96 hours postdose ]
    Vz is defined as the volume of distribution of the drug after intravenous administration.
  • PK Parameter: CL/F of GS-0976 [ Time Frame: Predose and up to 96 hours postdose ]
    CL/F is defined as the apparent oral clearance following administration of the drug.
  • PK Parameter: Vz/F of GS-0976 [ Time Frame: Predose and up to 96 hours postdose ]
    Vz/F is defined as the apparent volume of distribution of the drug.
  • PK Parameter: t1/2 of GS-0976 [ 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.
Change History Complete list of historical versions of study NCT02891408 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 1, 2016)
  • Incidence of adverse events [ Time Frame: Up to 31 days ]
  • Incidence of laboratory abnormalities [ Time Frame: Up to 31 days ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pharmacokinetics of Firsocostat or Fenofibrate in Adults With Normal and Impaired Hepatic Function
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Nonalcoholic Steatohepatitis (NASH)
Intervention  ICMJE
  • Drug: Firsocostat
    Tablet(s) or Capsule(s) administered orally on Day 1
    Other Name: GS-0976
  • Drug: Fenofibrate
    Tablet(s) administered orally on Day 1
Study Arms  ICMJE
  • 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).
    Intervention: Drug: Firsocostat
  • 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).
    Intervention: Drug: Firsocostat
  • 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).
    Intervention: Drug: Firsocostat
  • 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).
    Intervention: Drug: Fenofibrate
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 16, 2019)
74
Original Estimated Enrollment  ICMJE
 (submitted: September 1, 2016)
60
Actual Study Completion Date  ICMJE May 13, 2019
Actual Primary Completion Date May 5, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02891408
Other Study ID Numbers  ICMJE GS-US-426-3988
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Gilead Sciences
Study Sponsor  ICMJE Gilead Sciences
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Gilead Study Director Gilead Sciences
PRS Account Gilead Sciences
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP