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

NCT ID: NCT02654002

Last Updated: 2020-10-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-20
• Study Completion Date: 2016-07-14

Brief Summary

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).

Conditions

Nonalcoholic Steatohepatitis (NASH)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Cohort 1: Cilofexor 10 mg

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.

Group Type: EXPERIMENTAL

Cilofexor

Intervention Type: DRUG

Tablets administered orally

Placebo

Intervention Type: DRUG

Tablets administered orally

Cohort 2: Cilofexor 30 mg

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.

Group Type: EXPERIMENTAL

Cilofexor

Intervention Type: DRUG

Tablets administered orally

Placebo

Intervention Type: DRUG

Tablets administered orally

Cohort 3: Cilofexor 100 mg

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.

Group Type: EXPERIMENTAL

Cilofexor

Intervention Type: DRUG

Tablets administered orally

Placebo

Intervention Type: DRUG

Tablets administered orally

Cohort 4: Cilofexor 300 mg

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.

Group Type: EXPERIMENTAL

Cilofexor

Intervention Type: DRUG

Tablets administered orally

Placebo

Intervention Type: DRUG

Tablets administered orally

Cohort 5: Cilofexor 100 mg

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.

Group Type: EXPERIMENTAL

Cilofexor

Intervention Type: DRUG

Tablets administered orally

Placebo

Intervention Type: DRUG

Tablets administered orally

Cohort 6: Cilofexor 50 mg

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.

Group Type: EXPERIMENTAL

Cilofexor

Intervention Type: DRUG

Tablets administered orally

Placebo

Intervention Type: DRUG

Tablets administered orally

Cohort 7: Cilofexor 15 mg

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.

Group Type: EXPERIMENTAL

Cilofexor

Intervention Type: DRUG

Tablets administered orally

Placebo

Intervention Type: DRUG

Tablets administered orally

Cohort 8: Cilofexor 10 mg

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.

Group Type: EXPERIMENTAL

Cilofexor

Intervention Type: DRUG

Tablets administered orally

Placebo

Intervention Type: DRUG

Tablets administered orally

Cohort 9: Cilofexor

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

Group Type: EXPERIMENTAL

Cilofexor

Intervention Type: DRUG

Tablets administered orally

Placebo

Intervention Type: DRUG

Tablets administered orally

Cohort 10: Cilofexor

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

Group Type: EXPERIMENTAL

Cilofexor

Intervention Type: DRUG

Tablets administered orally

Placebo

Intervention Type: DRUG

Tablets administered orally

Interventions

Cilofexor

Tablets administered orally

Intervention Type: DRUG

Placebo

Tablets administered orally

Intervention Type: DRUG

Other Intervention Names

GS-9674

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

SeaView Research, Inc

Miami, Florida, United States

Countries

United States

References

Djedjos CS, Kirby BJ, Billin A, Gosink J, Song Q, Srihari R, et al. Pharmacodynamic Effects of the Oral, Non-Steroidal Farnesoid X Receptor Agonist GS-9674 in Healthy Volunteers. The 67th Annual Meeting of the American Association for the Study of Liver Diseases: The Liver Meeting (AASLD); 2016 November 11-15; Boston MA United States.

Reference Type: BACKGROUND

Kirby BJ, Djedjos CS, Birkeback J, Song Q, Grycz K, Weston J, et al. Evaluation of the Safety and Pharmacokinetics of the Oral, Nonsteroidal Farnesoid X Receptor Agonist GS-9674 in Healthy Volunteers. The 67th Annual Meeting of the American Association for the Study of Liver Diseases: The Liver Meeting (AASLD); 2016 November 11-15; Boston MA United States.

Reference Type: BACKGROUND

Other Identifiers

GS-US-402-1851

Identifier Type: -

Identifier Source: org_study_id