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

NCT02808312 | Completed Phase 1 Results FDA Drug

• 1 other identifier: GS-US-402-3885
• Study Type: interventional
• Target: 57
• Locations: 2 countries
• Sites: 5

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.

Conditions

Nonalcoholic Steatohepatitis (NASH); Primary Sclerosing Cholangitis (PSC)

Outcome Measures

Primary Outcomes (11)

• Pharmacokinetic (PK) Parameter: AUClast of Cilofexor

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

  ≤ 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.

  ≤ 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.

  ≤ 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.

  ≤ 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.

  ≤ 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.

  ≤ 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.

  ≤ 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.

  ≤ 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.

  ≤ 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.

  ≤ 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.

  ≤ 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

  Day 1 up to Day 31

• Percentage of Participants Who Experienced Graded Laboratory Abnormalities

  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)

  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)

  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)

  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

Study Arms (6)

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).

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).

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).

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).

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).

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).

Drug: Cilofexor

Interventions

Cilofexor DRUG

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

Also known as: GS-9674

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (5)

Unknown Facility

Miami, Florida, 33014, United States

Location

Unknown Facility

Orlando, Florida, 32809, United States

Location

Unknown Facility

Knoxville, Tennessee, 37920, United States

Location

Unknown Facility

San Antonio, Texas, 78215, United States

Location

Unknown Facility

Auckland, 1640, New Zealand

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Cholangitis, Sclerosing

Interventions

cilofexor

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Cholangitis; Bile Duct Diseases; Biliary Tract Diseases

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2016
• First Posted: June 21, 2016
• Study Start: July 13, 2016
• Primary Completion: October 16, 2018
• Study Completion: October 16, 2018
• Last Updated: January 7, 2021
• Results First Posted: September 30, 2020

Record last verified: 2020-12

Locations

US (4); NZ (1)