Study in Healthy Volunteers to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GS-9674 (Cilofexor), and the Effect of Food on GS-9674 Pharmacokinetics and Pharmacodynamics

Gilead Sciences

Status and phase

Completed

Phase 1

Conditions

Nonalcoholic Steatohepatitis (NASH)

Treatments

Drug: Placebo

Drug: Cilofexor

Study type

Interventional

Funder types

Industry

Identifiers

NCT02654002

GS-US-402-1851

Details and patient eligibility

About

This study will evaluate the safety and tolerability of escalating single- and multiple-oral doses of cilofexor, and characterize the single- and multiple-dose pharmacokinetics (PK) of cilofexor. The study will be conducted in 3 parts (Part A, Part B, and Part C). Participants will receive either cilofexor or cilofexor placebo.

Part A will proceed in 4 prespecified staggered cohorts. Within each cohort, the cumulative, blinded safety data will be evaluated for dose escalation from single-dose (Period 1) to multiple-dose (Period 2). Based on the available safety, pharmacokinetics, and/or pharmacodynamics (PD) data from cohorts in Part A and Part C (if applicable), total daily doses and frequency of dosing will be chosen for the cohorts in Part B. Parts B and C will consist of adaptive cohorts and may be initiated in parallel. Part B cohorts may be initiated in parallel with cohorts in Part A if the total dose under evaluation is at or below a dose already evaluated.

This study is partially blinded (no one is blinded on Day -1).

Enrollment

120 patients

Sex

All

Ages

18 to 45 years old

Volunteers

Accepts Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

Healthy male and non-pregnant, non-lactating female volunteers
Body mass index (BMI) 19 ≤ BMI ≤ 30 kg/m^2
Normal 12-lead electrocardiogram (ECG) or one with abnormalities that are considered clinically insignificant by the investigator
Normal renal function (estimated glomerular filtration rate calculated using the Cockcroft-Gault equation ≥ 80 mL/min)
No significant medical history, and in good general health as determined by the investigator at screening evaluation performed no more than 28 days prior to the scheduled first dose.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Double Blind

120 participants in 10 patient groups

Cohort 1: Cilofexor 10 mg

Experimental group

Description:

Participants in fasted state will receive cilofexor 10 mg or placebo once on Day 1 followed by a 5-day washout period then receive cilofexor 10 mg or placebo once daily from Day 7 to Day 20.

Treatment:

Drug: Cilofexor

Drug: Placebo

Cohort 2: Cilofexor 30 mg

Experimental group

Description:

Participants in fasted state will receive cilofexor 30 mg or placebo once on Day 1 followed by a 5-day washout period then receive cilofexor 30 mg or placebo once daily from Day 7 to Day 20.

Treatment:

Drug: Cilofexor

Drug: Placebo

Cohort 3: Cilofexor 100 mg

Experimental group

Description:

Participants in fasted state will receive cilofexor 100 mg or placebo once on Day 1 followed by a 5-day washout period then receive cilofexor 100 mg or placebo once daily from Day 7 to Day 20.

Treatment:

Drug: Cilofexor

Drug: Placebo

Cohort 4: Cilofexor 300 mg

Experimental group

Description:

Participants in fasted state will receive cilofexor 300 mg or placebo once on Day 1 followed by a 5-day washout period then receive cilofexor 300 mg or placebo once daily from Day 7 to Day 20.

Treatment:

Drug: Cilofexor

Drug: Placebo

Cohort 5: Cilofexor 100 mg

Experimental group

Description:

Participants in fed state will receive cilofexor 100 mg or placebo once with food on Day 1 followed by a 5-day washout period then receive cilofexor 100 mg or placebo tablet, orally, once daily with food from Day 7 to Day 20.

Treatment:

Drug: Cilofexor

Drug: Placebo

Cohort 6: Cilofexor 50 mg

Experimental group

Description:

Participants in fed state will receive cilofexor 50 mg or placebo twice with food on Day 1 followed by a 5-day washout period then receive cilofexor 50 mg or placebo twice daily from Day 7 to Day 20.

Treatment:

Drug: Cilofexor

Drug: Placebo

Cohort 7: Cilofexor 15 mg

Experimental group

Description:

Participants in fed state will receive cilofexor 15 mg or placebo twice with food on Day 1 followed by a 5-day washout period then receive cilofexor 15 mg or placebo twice daily from Day 7 to Day 20.

Treatment:

Drug: Cilofexor

Drug: Placebo

Cohort 8: Cilofexor 10 mg

Experimental group

Description:

Participants in fed state will receive cilofexor 10 mg or placebo once with food on Day 1 followed by a 5-day washout period then receive cilofexor 10 mg or placebo once daily from Day 7 to Day 20.

Treatment:

Drug: Cilofexor

Drug: Placebo

Cohort 9: Cilofexor

Experimental group

Description:

Participants will receive cilofexor up to 300 mg or placebo once daily in the evening on empty stomach.

Treatment:

Drug: Cilofexor

Drug: Placebo

Cohort 10: Cilofexor

Experimental group