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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02808312




Registration number
NCT02808312
Ethics application status
Date submitted
17/06/2016
Date registered
21/06/2016
Date last updated
7/01/2021

Titles & IDs
Public title
Pharmacokinetics and Pharmacodynamics of Cilofexor in Adults With Normal and Impaired Hepatic Function
Scientific 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
Secondary ID [1] 0 0
GS-US-402-3885
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Nonalcoholic Steatohepatitis (NASH) 0 0
Primary Sclerosing Cholangitis (PSC) 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Diet and Nutrition 0 0 0 0
Obesity
Infection 0 0 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cilofexor

Experimental: Cohort 1: Mild Hepatic Impairment - Participants with mild hepatic impairment will receive a single oral dose of cilofexor 30 mg (3 x 10 mg tablets).

Experimental: Cohort 1: Normal Hepatic Function - 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).

Experimental: Cohort 2: Moderate Hepatic Impairment - Participants with moderate hepatic impairment will receive a single oral dose of cilofexor 30 mg (3 x 10 mg tablets).

Experimental: Cohort 2: Normal Hepatic Function - 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).

Experimental: Cohort 3: Severe Hepatic Impairment - Participants with severe hepatic impairment will receive a single oral dose of cilofexor 10 mg (1 x 10 mg tablet).

Experimental: Cohort 3: Normal Hepatic Function - 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).


Treatment: Drugs: Cilofexor
Tablet(s) administered orally in a fed state on Day 1
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Pharmacokinetic (PK) Parameter: AUClast of Cilofexor
Timepoint [1] 0 0
= 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
Primary outcome [2] 0 0
PK Parameter: AUCinf of Cilofexor
Timepoint [2] 0 0
= 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
Primary outcome [3] 0 0
PK Parameter: Cmax of Cilofexor
Timepoint [3] 0 0
= 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
Primary outcome [4] 0 0
PK Parameter: %AUCexp of Cilofexor
Timepoint [4] 0 0
= 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
Primary outcome [5] 0 0
PK Parameter: Clast of Cilofexor
Timepoint [5] 0 0
= 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
Primary outcome [6] 0 0
PK Parameter: Tmax of Cilofexor
Timepoint [6] 0 0
= 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
Primary outcome [7] 0 0
PK Parameter: Tlast of Cilofexor
Timepoint [7] 0 0
= 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
Primary outcome [8] 0 0
PK Parameter: ?z of Cilofexor
Timepoint [8] 0 0
= 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
Primary outcome [9] 0 0
PK Parameter: CL/F of Cilofexor
Timepoint [9] 0 0
= 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
Primary outcome [10] 0 0
PK Parameter: Vz/F of Cilofexor
Timepoint [10] 0 0
= 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
Primary outcome [11] 0 0
PK Parameter: t1/2 of Cilofexor
Timepoint [11] 0 0
= 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 outcome [1] 0 0
Percentage of Participants Experiencing Treatment-Emergent Adverse Events
Timepoint [1] 0 0
Day 1 up to Day 31
Secondary outcome [2] 0 0
Percentage of Participants Who Experienced Graded Laboratory Abnormalities
Timepoint [2] 0 0
Day 1 up to Day 31
Secondary outcome [3] 0 0
Pharmacodynamic (PD) Parameter: Mean Day 1/ Day -1 Ratio of AUC2-12 for a-hydroxy-4-cholesten-3-one (C4)
Timepoint [3] 0 0
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
Secondary outcome [4] 0 0
PD Parameter: Mean Day 1/ Day -1 Ratio of Cmin for a-hydroxy-4-cholesten-3-one (C4)
Timepoint [4] 0 0
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
Secondary outcome [5] 0 0
PD Parameter: Mean Day 1/ Day -1 Ratio of AUC2-12 for Fibroblast Growth Factor 19 (FGF19)
Timepoint [5] 0 0
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
Secondary outcome [6] 0 0
PD Parameter: Mean Day 1/ Day -1 Ratio of Cmax for Fibroblast Growth Factor 19 (FGF19)
Timepoint [6] 0 0
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

Eligibility
Key inclusion criteria
Key

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/
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion criteria may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/07/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
16/10/2018
Sample size
Target
Accrual to date
Final
57
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Tennessee
Country [3] 0 0
United States of America
State/province [3] 0 0
Texas
Country [4] 0 0
New Zealand
State/province [4] 0 0
Auckland

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Gilead Sciences
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02808312
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Gilead Study Director
Address 0 0
Gilead Sciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/ct2/show/NCT02808312