Nonalcoholic Steatohepatitis (NASH)Phase 1NCT02654002

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

A Phase 1 study testing Cilofexor in people with Nonalcoholic Steatohepatitis (NASH), run by Gilead Sciences at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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). Read more about this study

Who is it for?: Ages 18 to 45 yearsHealthy volunteers can take part
Conditions the study is for: Nonalcoholic Steatohepatitis (NASH)
What is being tested?: Cilofexor
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 120 participants
Where: 1 siteUnited States
Study dates: 20 Jan 2016to 14 Jul 2016
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 45 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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.

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

SeaView Research, Inc
Miami, Florida

Other trials in United States

About this study

Official title: A Phase 1 Study in Healthy Volunteers to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GS-9674, and the Effect of Food on GS-9674 Pharmacokinetics and Pharmacodynamics

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)
Being tested: Cilofexor, Placebo
Medical subject headings: Non-alcoholic Fatty Liver Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CilofexorDrug
Also called GS-9674
Tablets administered orally
PlaceboDrug
Tablets administered orally

Study groups in NCT02654002
Study group	Role	What they receive
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. Receives: Drug: Cilofexor; Drug: 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. Receives: Drug: Cilofexor; Drug: 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. Receives: Drug: Cilofexor; Drug: 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. Receives: Drug: Cilofexor; Drug: 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. Receives: Drug: Cilofexor; Drug: 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. Receives: Drug: Cilofexor; Drug: 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. Receives: Drug: Cilofexor; Drug: 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. Receives: Drug: Cilofexor; Drug: Placebo
Cohort 9: Cilofexor	Experimental	Participants will receive cilofexor up to 300 mg or placebo once daily in the evening on empty stomach. Receives: Drug: Cilofexor; Drug: Placebo
Cohort 10: Cilofexor	Experimental	Participants will receive cilofexor up to 300 mg or placebo once daily in the evening on empty stomach. Receives: Drug: Cilofexor; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Single-Dose Pharmacokinetic (PK) Parameter: AUClast of Cilofexor
AUClast is defined as the concentration of drug from time zero to the last quantifiable concentration.
Measured: 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).
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
AUC2-12 is defined as the AUC from time 2 to 12 hours. The ratios calculated were normalized to Day -1. Participants received a single placebo tablet at Day -1 for Baseline. The ratio reported for Day 1 is the AUC2-12 Day 1 /AUC2-12 Day-1. The ratio reported for Day 20 is the AUC2-12 Day 20 /AUC2-12 Day-1.
Measured: 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
Cmax is defined as the maximum observed concentration of FGF19 in plasma. The ratios calculated were normalized to Day -1. Participants received a single placebo tablet at Day -1 for Baseline. The ratio reported for Day 1 is the Cmax Day 1 /Cmax Day-1. The ratio reported for Day 20 is the Cmax Day 20 /Cmax Day-1.
Measured: 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
AUC2-12 is defined as the AUC from time 2 to 12 hours. The ratios calculated were normalized to Day -1. Participants received a single placebo tablet at Day -1 for Baseline. The ratio reported for Day 1 is the AUC2-12 Day 1 /AUC2-12 Day-1. The ratio reported for Day 20 is the AUC2-12 Day 20 /AUC2-12 Day-1.
Measured: 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
Cmin is defined as the minimum observed concentration of C4 in plasma. The ratios calculated were normalized to Day -1. Participants received a single placebo tablet at Day -1 for Baseline. The ratio reported for Day 1 is the Cmin Day 1 /Cmin Day-1. The ratio reported for Day 20 is the Cmin Day 20 /Cmin Day-1.
Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

20 Jan 201614 Jul 2016

First posted13 Jan 2016 (estimated)
Study start20 Jan 2016
Primary completion14 Jul 2016
Study completion14 Jul 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Nonalcoholic Steatohepatitis (NASH)Studies of the same condition, open and under way.
More trials run by Gilead SciencesThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 120 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02654002
Sponsor's protocol ID: GS-US-402-1851
Status last verified: Sep 2020
First submitted: 11 Jan 2016
Last updated: 12 Oct 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

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.
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.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruiting
Efficacy of Carnitine Complex in Improving Hepatic Steatosis in Potential Liver Donors
Hepatic Steatosis, Fatty Liver
RecruitingPhase 3
A Study Evaluating Efruxifermin in Subjects With Non-Cirrhotic Nonalcoholic Steatohepatitis (NASH)/Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Fibrosis
NASH With Fibrosis, MASH With Fibrosis
Recruiting
NAFLD Clinical Care Pathway
NAFLD, MASLD
RecruitingPhase 3
Trial to Evaluate ALN-CIDEB in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Metabolic Dysfunction-Associated Steatotic Liver Disease, MASLD
RecruitingPhase 1
A Study of Efimosfermin Alfa in Adults With Hepatic Impairment
Non-alcoholic Fatty Liver Disease

All Nonalcoholic Steatohepatitis (NASH) trials

Study at a glance

From the registry record, last updated by the sponsor on 12 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1 Study in Healthy Volunteers to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GS-9674, and the Effect of Food on GS-9674 Pharmacokinetics and Pharmacodynamics
ClinicalTrials.gov ID: NCT02654002
Acronym / sponsor ID: GS-US-402-1851
Conditions: Nonalcoholic Steatohepatitis (NASH)
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 120 participants (actual)
Lead sponsor: Gilead SciencesIndustry (pharma, biotech, devices)
Study start: 20 Jan 2016 (actual)
Primary completion: 14 Jul 2016 (actual)
Study completion: 14 Jul 2016 (actual)
First posted: 13 Jan 2016 (estimated)
Results: Posted 12 Oct 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 10

Arm	Type	Receives
Cohort 1: Cilofexor 10 mg	Experimental	Drug: Cilofexor, Drug: PlaceboParticipants 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.
Cohort 2: Cilofexor 30 mg	Experimental	Drug: Cilofexor, Drug: PlaceboParticipants 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.
Cohort 3: Cilofexor 100 mg	Experimental	Drug: Cilofexor, Drug: PlaceboParticipants 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.
Cohort 4: Cilofexor 300 mg	Experimental	Drug: Cilofexor, Drug: PlaceboParticipants 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.
Cohort 5: Cilofexor 100 mg	Experimental	Drug: Cilofexor, Drug: PlaceboParticipants 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.
Cohort 6: Cilofexor 50 mg	Experimental	Drug: Cilofexor, Drug: PlaceboParticipants 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.
Cohort 7: Cilofexor 15 mg	Experimental	Drug: Cilofexor, Drug: PlaceboParticipants 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.
Cohort 8: Cilofexor 10 mg	Experimental	Drug: Cilofexor, Drug: PlaceboParticipants 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.
Cohort 9: Cilofexor	Experimental	Drug: Cilofexor, Drug: PlaceboParticipants will receive cilofexor up to 300 mg or placebo once daily in the evening on empty stomach.
Cohort 10: Cilofexor	Experimental	Drug: Cilofexor, Drug: PlaceboParticipants will receive cilofexor up to 300 mg or placebo once daily in the evening on empty stomach.

Who may qualify

Ages: 18 to 45 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (6 listed)

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.

Key exclusion criteria (0 listed)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
CilofexorAlso: GS-9674Tablets administered orally	Drug	Cohort 10: Cilofexor, Cohort 1: Cilofexor 10 mg, Cohort 2: Cilofexor 30 mg, Cohort 3: Cilofexor 100 mg, Cohort 4: Cilofexor 300 mg, Cohort 5: Cilofexor 100 mg, Cohort 6: Cilofexor 50 mg, Cohort 7: Cilofexor 15 mg, Cohort 8: Cilofexor 10 mg, Cohort 9: Cilofexor
PlaceboTablets administered orally	Drug	Cohort 10: Cilofexor, Cohort 1: Cilofexor 10 mg, Cohort 2: Cilofexor 30 mg, Cohort 3: Cilofexor 100 mg, Cohort 4: Cilofexor 300 mg, Cohort 5: Cilofexor 100 mg, Cohort 6: Cilofexor 50 mg, Cohort 7: Cilofexor 15 mg, Cohort 8: Cilofexor 10 mg, Cohort 9: Cilofexor

Primary outcome

Single-Dose Pharmacokinetic (PK) Parameter: AUClast of Cilofexor
Time frame: 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
AUClast is defined as the concentration of drug from time zero to the last quantifiable concentration.
Single-Dose PK Parameter: AUCinf of Cilofexor
Time frame: 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
AUCinf is defined as the concentration of drug extrapolated to infinite time (area under the plasma concentration versus time curve extrapolated to infinite time).
Single-Dose PK Parameter: Cmax of Cilofexor
Time frame: 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
Cmax is defined as the maximum observed concentration of drug in plasma.
Multiple-Dose PK Parameter: AUCtau of Cilofexor
Time frame: 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
AUCtau is the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval).
Multiple-Dose PK Parameter: Cmax of Cilofexor
Time frame: 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
Cmax is defined as the maximum observed concentration of drug in plasma.
Multiple-Dose PK Parameter: Ctau of Cilofexor
Time frame: 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
Ctau is defined as the observed drug concentration at the end of the dosing interval.
Percentage of Participants With at Least One Adverse Event (AE)
Time frame: First dose date up to last dose date (Maximum: 20 days) plus 30 days
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.
Percentage of Participants With Clinically Significant 12-Lead Electrocardiogram (ECG) Abnormalities
Time frame: First dose date up to last dose date (Maximum: 20 days) plus 30 days
Investigator determined the ECG findings were clinically significant.
Percentage of Participants With Clinical Laboratory Abnormalities
Time frame: First dose date up to last dose date (Maximum: 20 days) plus 30 days
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.

4 secondary outcomes

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

Results and safety

Results posted to the registry on 12 Oct 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cohort 1: Cilofexor 10 mg	12	12
Cohort 2: Cilofexor 30 mg	12	12
Cohort 3: Cilofexor 100 mg	12	12
Cohort 4: Cilofexor 300 mg	12	12
Cohort 5: Cilofexor 100 mg	12	12
Cohort 6: Cilofexor 50 mg	12	11
Cohort 7: Cilofexor 15 mg	12	11
Cohort 8: Cilofexor 10 mg	12	11
All Placebo	24	24

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

Time frame: 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. Mean (Standard Deviation). Unit: hours*nanogram/millilitre (h*ng/mL)

Measure	Cohort 1: Cilofexor 10 mg n = 12	Cohort 2: Cilofexor 30 mg n = 12	Cohort 3: Cilofexor 100 mg n = 12	Cohort 4: Cilofexor 300 mg n = 12	Cohort 5: Cilofexor 100 mg n = 12	Cohort 6: Cilofexor 50 mg n = 11	Cohort 7: Cilofexor 15 mg n = 12	Cohort 8: Cilofexor 10 mg n = 11
Value	1236.0 (384.65)	2450.6 (921.70)	7712.1 (7270.76)	12458.8 (4223.12)	4979.5 (2039.07)	3091.4 (752.66)	1301.9 (388.51)	905.9 (210.24)

Population analysed: The PK Analysis Set included all randomized participants who took at least 1 dose of Cilofexor and had at least 1 non-missing post-dose concentration value reported by the PK laboratory for each corresponding analyte.

Primary outcome: Single-Dose PK Parameter: AUCinf of Cilofexor

Time frame: 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. Mean (Standard Deviation). Unit: h*ng/mL

Measure	Cohort 1: Cilofexor 10 mg n = 12	Cohort 2: Cilofexor 30 mg n = 12	Cohort 3: Cilofexor 100 mg n = 12	Cohort 4: Cilofexor 300 mg n = 12	Cohort 5: Cilofexor 100 mg n = 12	Cohort 6: Cilofexor 50 mg n = 11	Cohort 7: Cilofexor 15 mg n = 12	Cohort 8: Cilofexor 10 mg n = 11
Value	1255.9 (382.37)	2473.4 (920.85)	7743.7 (7273.50)	12495.7 (4230.00)	5016.7 (2022.94)	3559.2 (1092.73)	1409.3 (428.33)	924.0 (216.60)

Population analysed: Participants in the PK Analysis Set were analyzed.

Primary outcome: Single-Dose PK Parameter: Cmax of Cilofexor

Time frame: 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. Mean (Standard Deviation). Unit: ng/mL

Measure	Cohort 1: Cilofexor 10 mg n = 12	Cohort 2: Cilofexor 30 mg n = 12	Cohort 3: Cilofexor 100 mg n = 12	Cohort 4: Cilofexor 300 mg n = 12	Cohort 5: Cilofexor 100 mg n = 12	Cohort 6: Cilofexor 50 mg n = 11	Cohort 7: Cilofexor 15 mg n = 12	Cohort 8: Cilofexor 10 mg n = 11
Value	304.2 (126.66)	580.2 (283.79)	2592.3 (3059.31)	3055.5 (2022.27)	927.6 (540.94)	665.9 (152.30)	340.2 (124.44)	209.8 (63.24)

Population analysed: Participants in the PK Analysis Set were analyzed.

Primary outcome: Multiple-Dose PK Parameter: AUCtau of Cilofexor

Time frame: 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. Mean (Standard Deviation). Unit: h*ng/mL

Measure	Cohort 1: Cilofexor 10 mg n = 12	Cohort 2: Cilofexor 30 mg n = 12	Cohort 3: Cilofexor 100 mg n = 12	Cohort 4: Cilofexor 300 mg n = 12	Cohort 5: Cilofexor 100 mg n = 12	Cohort 6: Cilofexor 50 mg n = 11	Cohort 7: Cilofexor 15 mg n = 11	Cohort 8: Cilofexor 10 mg n = 11
Value	1284.9 (460.35)	2891.0 (680.10)	6719.4 (3980.90)	8486.0 (4139.86)	4182.7 (1956.03)	3698.3 (837.91)	1293.5 (250.95)	848.2 (213.82)

Population analysed: Participants in the PK Analysis Set were analyzed.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: First dose date up to last dose date (Maximum: 20 days) plus 30 days. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cohort 1: Cilofexor 10 mg	0 of 12 (0%)	4 of 12 (33.3%)	0 of 12
Cohort 2: Cilofexor 30 mg	0 of 12 (0%)	3 of 12 (25%)	0 of 12
Cohort 3: Cilofexor 100 mg	0 of 12 (0%)	4 of 12 (33.3%)	0 of 12
Cohort 4: Cilofexor 300 mg	0 of 12 (0%)	3 of 12 (25%)	0 of 12
Cohort 5: Cilofexor 100 mg	0 of 12 (0%)	5 of 12 (41.7%)	0 of 12
Cohort 6: Cilofexor 50 mg	0 of 11 (0%)	3 of 11 (27.3%)	0 of 11
Cohort 7: Cilofexor 15 mg	0 of 12 (0%)	9 of 12 (75%)	0 of 12
Cohort 8: Cilofexor 10 mg	0 of 11 (0%)	2 of 11 (18.2%)	0 of 11
All Placebo	0 of 24 (0%)	6 of 24 (25%)	0 of 24

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
BackgroundDjedjos 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.
BackgroundKirby 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.

Related trials for Nonalcoholic Steatohepatitis (NASH)

Not yet recruiting
Efficacy of Carnitine Complex in Improving Hepatic Steatosis in Potential Liver Donors
Hepatic Steatosis, Fatty Liver
RecruitingPhase 3
A Study Evaluating Efruxifermin in Subjects With Non-Cirrhotic Nonalcoholic Steatohepatitis (NASH)/Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Fibrosis
NASH With Fibrosis, MASH With Fibrosis
Recruiting
NAFLD Clinical Care Pathway
NAFLD, MASLD
RecruitingPhase 3
Trial to Evaluate ALN-CIDEB in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Metabolic Dysfunction-Associated Steatotic Liver Disease, MASLD
RecruitingPhase 1
A Study of Efimosfermin Alfa in Adults With Hepatic Impairment
Non-alcoholic Fatty Liver Disease

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Gilead Study Director study director

Gilead Sciences

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cilofexor in people with Nonalcoholic Steatohepatitis (NASH), run by Gilead Sciences at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Oct 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Single-Dose Pharmacokinetic (PK) Parameter: AUClast of Cilofexor (time frame: 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). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02654002, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Oct 2020.