Nonalcoholic Steatohepatitis (NASH)Phase 1NCT02808312

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

A Phase 1 study testing Cilofexor in people with Nonalcoholic Steatohepatitis (NASH) and Primary Sclerosing Cholangitis (PSC), run by Gilead Sciences at 5 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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. Read more about this study

Who is it for?: Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for: Nonalcoholic Steatohepatitis (NASH), Primary Sclerosing Cholangitis (PSC)
What is being tested?: Cilofexor
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 57 participants
Where: 5 sitesin 2 countries
Study dates: 13 Jul 2016to 16 Oct 2018
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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.

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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.

Who cannot join

None listed.

Trial locations and contacts

5 sites in 2 countries.

Country

City, postcode or hospital

5 sites in 2 countries

United States4 sites

Study site
Knoxville, Tennessee, 37920
Study site
Miami, Florida, 33014
Study site
Orlando, Florida, 32809
Study site
San Antonio, Texas, 78215

Other trials in United States

New Zealand1 site

Study site
Auckland, 1640

Other trials in New Zealand

About this study

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

Conditions: Nonalcoholic Steatohepatitis (NASH), Primary Sclerosing Cholangitis (PSC)
Being tested: Cilofexor
Medical subject headings: Non-alcoholic Fatty Liver Disease, Cholangitis, Sclerosing

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CilofexorDrug
Also called GS-9674
Tablet(s) administered orally in a fed state on Day 1

Study groups in NCT02808312
Study group	Role	What they receive
Cohort 1: Mild Hepatic Impairment	Experimental	Participants with mild hepatic impairment will receive a single oral dose of cilofexor 30 mg (3 x 10 mg tablets). Receives: Drug: Cilofexor
Cohort 1: Normal Hepatic Function	Experimental	Matched normal hepatic function participants to mild hepatic impairment participants will receive a single oral dose of cilofexor 30 mg (3 x 10 mg tablets). Receives: Drug: Cilofexor
Cohort 2: Moderate Hepatic Impairment	Experimental	Participants with moderate hepatic impairment will receive a single oral dose of cilofexor 30 mg (3 x 10 mg tablets). Receives: Drug: Cilofexor
Cohort 2: Normal Hepatic Function	Experimental	Matched normal hepatic function participants to moderate hepatic impairment participants will receive a single oral dose of cilofexor 30 mg (3 x 10 mg tablets). Receives: Drug: Cilofexor
Cohort 3: Severe Hepatic Impairment	Experimental	Participants with severe hepatic impairment will receive a single oral dose of cilofexor 10 mg (1 x 10 mg tablet). Receives: Drug: Cilofexor
Cohort 3: Normal Hepatic Function	Experimental	Matched normal hepatic function participants to severe hepatic impairment participants will receive a single oral dose of cilofexor 10 mg (1 x 10 mg tablet). Receives: Drug: Cilofexor

What is being measured

The primary outcome is the main question the study is designed to answer.

Pharmacokinetic (PK) Parameter: AUClast of Cilofexor
AUClast is defined as the concentration of drug from time zero to the last observable concentration.
Measured: ≤ 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
PK Parameter: AUCinf of Cilofexor
AUCinf is defined as the concentration of drug extrapolated to infinite time.
Measured: ≤ 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
PK Parameter: Cmax of Cilofexor
Cmax is defined as the maximum concentration of drug.
Measured: ≤ 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
PK Parameter: %AUCexp of Cilofexor
%AUCexp is defined as the percentage of AUC extrapolated between AUClast and AUCinf.
Measured: ≤ 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
PK Parameter: Clast of Cilofexor
Clast is defined as the last observable concentration of drug.
Measured: ≤ 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
PK Parameter: Tmax of Cilofexor
Tmax is defined as the time (observed time point) of Cmax.
Measured: ≤ 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
PK Parameter: Tlast of Cilofexor
Tlast is defined as the time (observed time point) of Clast.
Measured: ≤ 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
PK Parameter: λz of Cilofexor
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.
Measured: ≤ 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
PK Parameter: CL/F of Cilofexor
CL/F is defined as the apparent oral clearance following administration of the drug.
Measured: ≤ 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
PK Parameter: Vz/F of Cilofexor
Vz/F is defined as the apparent volume of distribution of the drug.
Measured: ≤ 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
PK Parameter: t1/2 of Cilofexor
t1/2 is defined as the estimate of the terminal elimination half-life of the drug.
Measured: ≤ 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

Secondary outcomes (6)

Percentage of Participants Experiencing Treatment-Emergent Adverse Events
Measured: Day 1 up to Day 31
Percentage of Participants Who Experienced Graded Laboratory Abnormalities
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.
Measured: Day 1 up to Day 31
Pharmacodynamic (PD) Parameter: Mean Day 1/ Day -1 Ratio of AUC2-12 for α-hydroxy-4-cholesten-3-one (C4)
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.
Measured: 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
PD Parameter: Mean Day 1/ Day -1 Ratio of Cmin for α-hydroxy-4-cholesten-3-one (C4)
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.
Measured: 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
PD Parameter: Mean Day 1/ Day -1 Ratio of AUC2-12 for Fibroblast Growth Factor 19 (FGF19)
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.
Measured: 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
PD Parameter: Mean Day 1/ Day -1 Ratio of Cmax for Fibroblast Growth Factor 19 (FGF19)
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.
Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

13 Jul 201616 Oct 2018

First posted21 Jun 2016 (estimated)
Study start13 Jul 2016
Primary completion16 Oct 2018
Study completion16 Oct 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Nonalcoholic Steatohepatitis (NASH)Studies of the same condition, open and under way.
More trials run by Gilead SciencesThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 57 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02808312
Sponsor's protocol ID: GS-US-402-3885
Status last verified: Dec 2020
First submitted: 17 Jun 2016
Last updated: 7 Jan 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 7 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT02808312
Acronym / sponsor ID: GS-US-402-3885
Conditions: Nonalcoholic Steatohepatitis (NASH), Primary Sclerosing Cholangitis (PSC)
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 57 participants (actual)
Lead sponsor: Gilead SciencesIndustry (pharma, biotech, devices)
Study start: 13 Jul 2016 (actual)
Primary completion: 16 Oct 2018 (actual)
Study completion: 16 Oct 2018 (actual)
First posted: 21 Jun 2016 (estimated)
Results: Posted 30 Sep 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 6

Arm	Type	Receives
Cohort 1: Mild Hepatic Impairment	Experimental	Drug: CilofexorParticipants with mild hepatic impairment will receive a single oral dose of cilofexor 30 mg (3 x 10 mg tablets).
Cohort 1: Normal Hepatic Function	Experimental	Drug: CilofexorMatched normal hepatic function participants to mild hepatic impairment participants will receive a single oral dose of cilofexor 30 mg (3 x 10 mg tablets).
Cohort 2: Moderate Hepatic Impairment	Experimental	Drug: CilofexorParticipants with moderate hepatic impairment will receive a single oral dose of cilofexor 30 mg (3 x 10 mg tablets).
Cohort 2: Normal Hepatic Function	Experimental	Drug: CilofexorMatched normal hepatic function participants to moderate hepatic impairment participants will receive a single oral dose of cilofexor 30 mg (3 x 10 mg tablets).
Cohort 3: Severe Hepatic Impairment	Experimental	Drug: CilofexorParticipants with severe hepatic impairment will receive a single oral dose of cilofexor 10 mg (1 x 10 mg tablet).
Cohort 3: Normal Hepatic Function	Experimental	Drug: CilofexorMatched normal hepatic function participants to severe hepatic impairment participants will receive a single oral dose of cilofexor 10 mg (1 x 10 mg tablet).

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (10 listed)

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.
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.
Individuals with severely impaired and normal hepatic function.

Key exclusion criteria (0 listed)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
CilofexorAlso: GS-9674Tablet(s) administered orally in a fed state on Day 1	Drug	Cohort 1: Mild Hepatic Impairment, Cohort 1: Normal Hepatic Function, Cohort 2: Moderate Hepatic Impairment, Cohort 2: Normal Hepatic Function, Cohort 3: Normal Hepatic Function, Cohort 3: Severe Hepatic Impairment

Primary outcome

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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.

6 secondary outcomes

Percentage of Participants Experiencing Treatment-Emergent Adverse Events
Time frame: Day 1 up to Day 31
Percentage of Participants Who Experienced Graded Laboratory Abnormalities
Time frame: Day 1 up to Day 31
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
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
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
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

Results and safety

Results posted to the registry on 30 Sep 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cohort 1: Mild Hepatic Impairment	10	10
Cohort 2: Moderate Hepatic Impairment	10	10
Cohort 1 & 2: Normal Hepatic Function	17	16
Cohort 3: Severe Hepatic Impairment	10	10
Cohort 3: Normal Hepatic Function	10	10

Primary outcome: 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. Mean (Standard Deviation). Unit: h*ng/mL

Measure	Cohort 1: Mild Hepatic Impairment n = 10	Cohort 1: Normal Hepatic Function n = 10	Cohort 2: Moderate Hepatic Impairment n = 10	Cohort 2: Normal Hepatic Function n = 10	Cohort 3: Severe Hepatic Impairment n = 10	Cohort 3: Normal Hepatic Function n = 10
Value	5381.0 (2175.34)	2972.6 (1230.49)	8223.7 (7492.41)	2756.7 (851.38)	6534.3 (3791.05)	960.0 (352.71)

Cohort 1: Mild Hepatic Impairment vs Cohort 1: Normal Hepatic Function: GLSM ratio: 1.7869 (90% CI 1.2885 to 2.4781)
Cohort 2: Moderate Hepatic Impairment vs Cohort 2: Normal Hepatic Function: GLSM ratio: 2.4868 (90% CI 1.6735 to 3.6954)
Cohort 3: Severe Hepatic Impairment vs Cohort 3: Normal Hepatic Function: GLSM ratio: 6.3240 (90% CI 4.3675 to 9.1569)

Population analysed: The 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 the PK laboratory for the corresponding analytes. A participant with normal hepatic function might serve as a matched control across cohorts evaluating the same cilofexor dose.

Primary outcome: 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. Mean (Standard Deviation). Unit: h*ng/mL

Measure	Cohort 1: Mild Hepatic Impairment n = 10	Cohort 1: Normal Hepatic Function n = 10	Cohort 2: Moderate Hepatic Impairment n = 10	Cohort 2: Normal Hepatic Function n = 10	Cohort 3: Severe Hepatic Impairment n = 10	Cohort 3: Normal Hepatic Function n = 10
Value	5411.9 (2181.82)	3024.3 (1224.02)	8288.2 (7583.42)	2805.6 (851.26)	6719.4 (4056.73)	986.2 (354.93)

Cohort 1: Mild Hepatic Impairment vs Cohort 1: Normal Hepatic Function: GLSM ratio: 1.7628 (90% CI 1.2750 to 2.4374)
Cohort 2: Moderate Hepatic Impairment vs Cohort 2: Normal Hepatic Function: GLSM ratio: 2.4559 (90% CI 1.6531 to 3.6486)
Cohort 3: Severe Hepatic Impairment vs Cohort 3: Normal Hepatic Function: GLSM ratio: 6.2497 (90% CI 4.2965 to 9.0910)

Population analysed: Participants in the PK Analysis Set were analyzed. A participant with normal hepatic function might serve as a matched control across cohorts evaluating the same cilofexor dose.

Primary outcome: 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. Mean (Standard Deviation). Unit: ng/mL

Measure	Cohort 1: Mild Hepatic Impairment n = 10	Cohort 1: Normal Hepatic Function n = 10	Cohort 2: Moderate Hepatic Impairment n = 10	Cohort 2: Normal Hepatic Function n = 10	Cohort 3: Severe Hepatic Impairment n = 10	Cohort 3: Normal Hepatic Function n = 10
Value	994.1 (533.38)	603.5 (275.33)	909.2 (477.20)	495.7 (199.45)	426.6 (136.40)	182.4 (86.67)

Cohort 1: Mild Hepatic Impairment vs Cohort 1: Normal Hepatic Function: GLSM ratio: 1.5703 (90% CI 1.0723 to 2.2995)
Cohort 2: Moderate Hepatic Impairment vs Cohort 2: Normal Hepatic Function: GLSM ratio: 1.7343 (90% CI 1.2193 to 2.4667)
Cohort 3: Severe Hepatic Impairment vs Cohort 3: Normal Hepatic Function: GLSM ratio: 2.5369 (90% CI 1.7562 to 3.6648)

Population analysed: Participants in the PK Analysis Set were analyzed. A participant with normal hepatic function might serve as a matched control across cohorts evaluating the same cilofexor dose.

Primary outcome: 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. Mean (Standard Deviation). Unit: percentage of AUCexp

Measure	Cohort 1: Mild Hepatic Impairment n = 10	Cohort 1: Normal Hepatic Function n = 10	Cohort 2: Moderate Hepatic Impairment n = 10	Cohort 2: Normal Hepatic Function n = 10	Cohort 3: Severe Hepatic Impairment n = 10	Cohort 3: Normal Hepatic Function n = 10
Value	0.63 (0.270)	1.95 (1.621)	0.64 (0.194)	1.87 (1.653)	1.81 (1.874)	2.96 (1.962)

Population analysed: Participants in the PK Analysis Set were analyzed. A participant with normal hepatic function might serve as a matched control across cohorts evaluating the same cilofexor dose.

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: Day 1 up to Day 31. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cohort 1: Mild Hepatic Impairment	0 of 10 (0%)	1 of 10 (10%)	0 of 10
Cohort 2: Moderate Hepatic Impairment	1 of 10 (10%)	1 of 10 (10%)	0 of 10
Cohort 1 and 2: Normal Hepatic Function	0 of 16 (0%)	2 of 16 (12.5%)	0 of 16
Cohort 3: Severe Hepatic Impairment	1 of 10 (10%)	2 of 10 (20%)	0 of 10
Cohort 3: Normal Hepatic Function	0 of 10 (0%)	0 of 10 (0%)	0 of 10

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Jan 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Gilead Study Director study director

Gilead Sciences

5 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cilofexor in people with Nonalcoholic Steatohepatitis (NASH) and Primary Sclerosing Cholangitis (PSC), run by Gilead Sciences at 5 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States, New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Sep 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02808312.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jan 2021.