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Pharmacokinetics and Pharmacodynamics of GS-9674 in Adults With Normal and Impaired Hepatic Function

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ClinicalTrials.gov Identifier: NCT02808312
Recruitment Status : Completed
First Posted : June 21, 2016
Last Update Posted : October 30, 2018
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Brief Summary:
The primary objective of this study is to evaluate the single-dose pharmacokinetics of GS-9674 in adults with impaired hepatic function relative to matched, healthy controls with normal hepatic function.

Condition or disease Intervention/treatment Phase
Nonalcoholic Steatohepatitis (NASH) Drug: GS-9674 (30 mg) Drug: GS-9674 (10 mg) Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 57 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Open-Label, Parallel-Group, Adaptive, Single-Dose Study to Evaluate the Pharmacokinetics and Pharmacodynamics of GS-9674 in Subjects With Normal and Impaired Hepatic Function
Actual Study Start Date : July 13, 2016
Actual Primary Completion Date : October 16, 2018
Actual Study Completion Date : October 16, 2018


Arm Intervention/treatment
Experimental: Mild Hepatic Impairment (Cohort 1)
Participants with mild hepatic impairment and matched healthy controls will receive a single dose of GS-9674 (30 mg) on Day 1.
Drug: GS-9674 (30 mg)
GS-9674 30 mg (3 x 10 mg tablet) orally

Experimental: Moderate Hepatic Impairment (Cohort 2)
Participants with moderate hepatic impairment and matched healthy controls will receive a single dose of GS-9674 (30 mg) on Day 1.
Drug: GS-9674 (30 mg)
GS-9674 30 mg (3 x 10 mg tablet) orally

Experimental: Severe Hepatic Impairment (Cohort 3)
Participants with severe hepatic impairment and matched healthy controls will receive a single dose of GS-9674 (10 mg) on Day 1.
Drug: GS-9674 (10 mg)
GS-9674 10 mg (1 x 10 mg tablet) orally




Primary Outcome Measures :
  1. Pharmacokinetic (PK) Parameter: AUClast of GS-9674 [ 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 GS-9674 [ 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 GS-9674 [ Time Frame: Predose and up to 96 hours postdose ]
    Cmax is defined as the maximum concentration of drug.

  4. PK Parameter: %AUCexp of GS-9674 [ Time Frame: Predose and up to 96 hours postdose ]
    %AUCexp is defined as the percentage of area under the curve (AUC) extrapolated between AUClast and AUCinf.

  5. PK Parameter: Clast of GS-9674 [ Time Frame: Predose and up to 96 hours postdose ]
    Clast is defined as the last observable concentration of drug.

  6. PK Parameter: Tmax of GS-9674 [ Time Frame: Predose and up to 96 hours postdose ]
    Tmax is defined as the time (observed time point) of Cmax.

  7. PK Parameter: Tlast of GS-9674 [ 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 GS-9674 [ 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 GS-9674 [ 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 GS-9674 [ 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 GS-9674 [ 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. Incidences of Adverse Events [ Time Frame: Up to 30 days posttreatment ]
  2. Changes from Baseline in Pharmacodynamic (PD) Markers such as FGF19 and C4 [ Time Frame: Predose and up to 96 hours postdose ]


Information from the National Library of Medicine

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

Key Inclusion Criteria:

Cohort 1:

  • Individuals with mildly impaired and normal hepatic function.
  • Individuals with mild hepatic impairment must have a score of 5-6 on the CPT Classification at Screening without evidence of worsening clinical and/or laboratory signs of hepatic impairment within 2 months prior or within the screening period.

Cohort 2:

  • Individuals with moderately impaired and normal hepatic function.
  • Individuals with moderate hepatic impairment must have a score of 7-9 on the CPT Classification at Screening without evidence of worsening clinical and/or laboratory signs of hepatic impairment within 2 months prior or within the screening period.

Cohort 3:

  • Individuals with severely impaired and normal hepatic function.
  • Individuals with severe hepatic impairment must have a score of 10-15 on the CPT Classification at Screening without evidence of worsening clinical and/or laboratory signs of hepatic impairment within 2 months prior or within the screening period.

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): NCT02808312


Locations
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United States, Florida
Miami, Florida, United States, 33014
Orlando, Florida, United States, 32809
United States, Tennessee
Knoxville, Tennessee, United States, 37920
United States, Texas
San Antonio, Texas, United States, 78215
New Zealand
Auckland, New Zealand, 1640
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: NCT02808312     History of Changes
Other Study ID Numbers: GS-US-402-3885
First Posted: June 21, 2016    Key Record Dates
Last Update Posted: October 30, 2018
Last Verified: October 2018
Additional relevant MeSH terms:
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Fatty Liver
Non-alcoholic Fatty Liver Disease
Liver Diseases
Digestive System Diseases