NCT02654002

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).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
120

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Jan 2016

Shorter than P25 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 11, 2016

Completed
2 days until next milestone

First Posted

Study publicly available on registry

January 13, 2016

Completed
7 days until next milestone

Study Start

First participant enrolled

January 20, 2016

Completed
6 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 14, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 14, 2016

Completed
4.2 years until next milestone

Results Posted

Study results publicly available

October 12, 2020

Completed
Last Updated

October 12, 2020

Status Verified

September 1, 2020

Enrollment Period

6 months

First QC Date

January 11, 2016

Results QC Date

September 16, 2020

Last Update Submit

September 16, 2020

Conditions

Nonalcoholic Steatohepatitis (NASH)

Outcome Measures

Primary Outcomes (9)

  • Single-Dose Pharmacokinetic (PK) Parameter: AUClast of Cilofexor

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

    Day 1: -0.5, 0 (pre-dose), 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 post-dose

  • Single-Dose PK Parameter: AUCinf of Cilofexor

    AUCinf is defined as the concentration of drug extrapolated to infinite time (area under the plasma concentration versus time curve extrapolated to infinite time).

    Day 1: -0.5, 0 (pre-dose), 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 post-dose

  • Single-Dose PK Parameter: Cmax of Cilofexor

    Cmax is defined as the maximum observed concentration of drug in plasma.

    Day 1: -0.5, 0 (pre-dose), 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 post-dose

  • Multiple-Dose PK Parameter: AUCtau of Cilofexor

    AUCtau is the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval).

    Day 20: -0.5, 0 (pre-dose), 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 post-dose

  • Multiple-Dose PK Parameter: Cmax of Cilofexor

    Cmax is defined as the maximum observed concentration of drug in plasma.

    Day 20: -0.5, 0 (pre-dose), 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 post-dose

  • Multiple-Dose PK Parameter: Ctau of Cilofexor

    Ctau is defined as the observed drug concentration at the end of the dosing interval.

    Day 20: -0.5, 0 (pre-dose), 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 post-dose

  • Percentage of Participants With at Least One Adverse Event (AE)

    An AE is any untoward medical occurrence in a clinical study participant administered a medicinal product, which does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

    First dose date up to last dose date (Maximum: 20 days) plus 30 days

  • Percentage of Participants With Clinically Significant 12-Lead Electrocardiogram (ECG) Abnormalities

    Investigator determined the ECG findings were clinically significant.

    First dose date up to last dose date (Maximum: 20 days) plus 30 days

  • Percentage of Participants With Clinical Laboratory Abnormalities

    Treatment-emergent laboratory (Hematology, Chemistry, and Urinalysis) abnormalities were defined as values that increase at least one toxicity grade from baseline. Laboratory Abnormalities are graded by the investigator as Grade 1, 2, 3, or 4 according to the modified Gilead Sciences, Inc (GSI) Grading Scale. The most severe graded abnormality from all tests was counted for each participant. Data is only reported for those Grades reported in 1 or more participants.

    First dose date up to last dose date (Maximum: 20 days) plus 30 days

Secondary Outcomes (4)

  • Pharmacodynamic (PD) Parameter: Fibroblast Growth Factor 19 (FGF19) AUC2-12 Ratio

    Day -1: -0.5, 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, and 16 hours post-dose; Days 1, and 20: -0.5, 0 (pre-dose), 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 post-dose

  • PD Parameter: FGF19 Cmax Ratio

    Day -1: -0.5, 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, and 16 hours post-dose; Days 1, and 20: -0.5, 0 (pre-dose), 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 post-dose

  • PD Parameter: 7alpha-hydroxy-4-cholesten-3-one (C4) AUC2-12 Ratio

    Day -1: -0.5, 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, and 16 hours post-dose; Days 1, and 20: -0.5, 0 (pre-dose), 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 post-dose

  • PD Parameter: C4 Cmin Ratio

    Day -1: -0.5, 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, and 16 hours post-dose; Days 1, and 20: -0.5, 0 (pre-dose), 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 post-dose

Study Arms (10)

Cohort 1: Cilofexor 10 mg

EXPERIMENTAL

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.

Drug: CilofexorDrug: Placebo

Cohort 2: Cilofexor 30 mg

EXPERIMENTAL

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.

Drug: CilofexorDrug: Placebo

Cohort 3: Cilofexor 100 mg

EXPERIMENTAL

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.

Drug: CilofexorDrug: Placebo

Cohort 4: Cilofexor 300 mg

EXPERIMENTAL

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.

Drug: CilofexorDrug: Placebo

Cohort 5: Cilofexor 100 mg

EXPERIMENTAL

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.

Drug: CilofexorDrug: Placebo

Cohort 6: Cilofexor 50 mg

EXPERIMENTAL

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.

Drug: CilofexorDrug: Placebo

Cohort 7: Cilofexor 15 mg

EXPERIMENTAL

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.

Drug: CilofexorDrug: Placebo

Cohort 8: Cilofexor 10 mg

EXPERIMENTAL

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.

Drug: CilofexorDrug: Placebo

Cohort 9: Cilofexor

EXPERIMENTAL

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

Drug: CilofexorDrug: Placebo

Cohort 10: Cilofexor

EXPERIMENTAL

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

Drug: CilofexorDrug: Placebo

Interventions

CilofexorDRUG

Tablets administered orally

Also known as: GS-9674
Cohort 10: CilofexorCohort 1: Cilofexor 10 mgCohort 2: Cilofexor 30 mgCohort 3: Cilofexor 100 mgCohort 4: Cilofexor 300 mgCohort 5: Cilofexor 100 mgCohort 6: Cilofexor 50 mgCohort 7: Cilofexor 15 mgCohort 8: Cilofexor 10 mgCohort 9: Cilofexor
PlaceboDRUG

Tablets administered orally

Cohort 10: CilofexorCohort 1: Cilofexor 10 mgCohort 2: Cilofexor 30 mgCohort 3: Cilofexor 100 mgCohort 4: Cilofexor 300 mgCohort 5: Cilofexor 100 mgCohort 6: Cilofexor 50 mgCohort 7: Cilofexor 15 mgCohort 8: Cilofexor 10 mgCohort 9: Cilofexor

Eligibility Criteria

Age18 Years - 45 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

SeaView Research, Inc

Miami, Florida, United States

Location

Related Publications (2)

  • 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.

    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.

    BACKGROUND

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

cilofexor

Condition Hierarchy (Ancestors)

Fatty LiverLiver DiseasesDigestive System 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
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 11, 2016

First Posted

January 13, 2016

Study Start

January 20, 2016

Primary Completion

July 14, 2016

Study Completion

July 14, 2016

Last Updated

October 12, 2020

Results First Posted

October 12, 2020

Record last verified: 2020-09

Locations

US(1)