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Completed

NCT Number: NCT02808312

Pharmacokinetics and Pharmacodynamics of Cilofexor in Adults With Normal and Impaired Hepatic Function

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

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Key information

Conditions

Nonalcoholic Steatohepatitis (NASH) Bile Duct Diseases Biliary Tract Diseases Cholangitis Cholangitis, Sclerosing Digestive System Diseases Fatty Liver Liver Diseases Non-alcoholic Fatty Liver Disease Primary Sclerosing Cholangitis (PSC)

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Auckland, New Zealand

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Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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 Child-Pugh-Turcotte (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.

Treatment and study plan

Cilofexor

Drug

Tablet(s) administered orally in a fed state on Day 1

Other names: GS-9674

Primary outcomes

  1. Pharmacokinetic (PK) Parameter: AUClast of Cilofexor

    Time frame: ≤ 5 minutes predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, and 96 hours postdose on Day 1

    AUClast is defined as the concentration of drug from time zero to the last observable concentration.

  2. PK Parameter: AUCinf of Cilofexor

    Time frame: ≤ 5 minutes predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, and 96 hours postdose on Day 1

    AUCinf is defined as the concentration of drug extrapolated to infinite time.

  3. PK Parameter: Cmax of Cilofexor

    Time frame: ≤ 5 minutes predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, and 96 hours postdose on Day 1

    Cmax is defined as the maximum concentration of drug.

  4. PK Parameter: %AUCexp of Cilofexor

    Time frame: ≤ 5 minutes predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, and 96 hours postdose on Day 1

    %AUCexp is defined as the percentage of AUC extrapolated between AUClast and AUCinf.

  5. PK Parameter: Clast of Cilofexor

    Time frame: ≤ 5 minutes predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, and 96 hours postdose on Day 1

    Clast is defined as the last observable concentration of drug.

  6. PK Parameter: Tmax of Cilofexor

    Time frame: ≤ 5 minutes predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, and 96 hours postdose on Day 1

    Tmax is defined as the time (observed time point) of Cmax.

  7. PK Parameter: Tlast of Cilofexor

    Time frame: ≤ 5 minutes predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, and 96 hours postdose on Day 1

    Tlast is defined as the time (observed time point) of Clast.

  8. PK Parameter: λz of Cilofexor

    Time frame: ≤ 5 minutes predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, and 96 hours postdose on Day 1

    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 Cilofexor

    Time frame: ≤ 5 minutes predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, and 96 hours postdose on Day 1

    CL/F is defined as the apparent oral clearance following administration of the drug.

  10. PK Parameter: Vz/F of Cilofexor

    Time frame: ≤ 5 minutes predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, and 96 hours postdose on Day 1

    Vz/F is defined as the apparent volume of distribution of the drug.

  11. PK Parameter: t1/2 of Cilofexor

    Time frame: ≤ 5 minutes predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, and 96 hours postdose on Day 1

    t1/2 is defined as the estimate of the terminal elimination half-life of the drug.

Secondary outcomes

  1. Percentage of Participants Experiencing Treatment-Emergent Adverse Events

    Time frame: Day 1 up to Day 31

  2. Percentage of Participants Who Experienced Graded Laboratory Abnormalities

    Time frame: Day 1 up to Day 31

    A treatment-emergent laboratory abnormality was defined as an increase of at least 1 toxicity grade from predose at any time postdose up to and including the date of last study drug dose plus 30 days. The most severe graded abnormality from all tests was counted for each participant.

  3. Pharmacodynamic (PD) Parameter: Mean Day 1/ Day -1 Ratio of AUC2-12 for α-hydroxy-4-cholesten-3-one (C4)

    Time frame: 0.5 hour predose, ≤ 5 minutes predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, and 16 hours postdose on Day -1 and Day 1; 4.5 hours postdose on Day -1; 24, 48, 72, and 96 hours postdose on Day 1

    AUC2-12 is defined as area under the curve calculated by the trapezoidal rule for the time from 2 to 12 hours. For PD assessments on Day -1, participants were administered a single oral dose of placebo-to-match cilofexor tablet on Day -1; the reported Time Frame is with respect to the placebo dosing.

  4. PD Parameter: Mean Day 1/ Day -1 Ratio of Cmin for α-hydroxy-4-cholesten-3-one (C4)

    Time frame: 0.5 hour predose, ≤ 5 minutes predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, and 16 hours postdose on Day -1 and Day 1; 4.5 hours postdose on Day -1; 24, 48, 72, and 96 hours postdose on Day 1

    Cmin for C4 is defined as the minimum observed concentration of C4. For PD assessments on Day -1, participants were administered a single oral dose of placebo-to-match cilofexor tablet on Day -1; the reported Time Frame is with respect to the placebo dosing.

  5. PD Parameter: Mean Day 1/ Day -1 Ratio of AUC2-12 for Fibroblast Growth Factor 19 (FGF19)

    Time frame: 0.5 hour predose, ≤ 5 minutes predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, and 16 hours postdose on Day -1 and Day 1; 4.5 hours postdose on Day -1; 24, 48, 72, and 96 hours postdose on Day 1

    AUC2-12 is defined as area under the curve calculated by the trapezoidal rule for the time from 2 to 12 hours. For PD assessments on Day -1, participants were administered a single oral dose of placebo-to-match cilofexor tablet on Day -1; the reported Time Frame is with respect to the placebo dosing.

  6. PD Parameter: Mean Day 1/ Day -1 Ratio of Cmax for Fibroblast Growth Factor 19 (FGF19)

    Time frame: 0.5 hour predose, ≤ 5 minutes predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, and 16 hours postdose on Day -1 and Day 1; 4.5 hours postdose on Day -1; 24, 48, 72, and 96 hours postdose on Day 1

    Cmax for FGF19 is defined as the maximum observed concentration of FGF19. For PD assessments on Day -1, participants were administered a single oral dose of placebo-to-match cilofexor tablet on Day -1; the reported Time Frame is with respect to the placebo dosing.

Sponsors and collaborators

Lead sponsor

Gilead Sciences

Industry

Registry information

Official study 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

Important dates

Study start
2016
Primary completion
2018
Study completion
2018
First posted
Jun 21, 2016
Registry last updated
Jan 7, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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