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
Sponsor
Gilead Sciences (Industry)
Overall Status
Completed
CT.gov ID
NCT02654002
Collaborator
(none)
120
1
10
5.8
20.8
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
120 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
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
Actual Study Start Date
:
Jan 20, 2016
Actual Primary Completion Date
:
Jul 14, 2016
Actual Study Completion Date
:
Jul 14, 2016
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. |
Drug: Cilofexor
Tablets administered orally
Other Names:
Drug: Placebo
Tablets administered orally
|
| Experimental: 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. |
Drug: Cilofexor
Tablets administered orally
Other Names:
Drug: Placebo
Tablets administered orally
|
| Experimental: 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. |
Drug: Cilofexor
Tablets administered orally
Other Names:
Drug: Placebo
Tablets administered orally
|
| Experimental: 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. |
Drug: Cilofexor
Tablets administered orally
Other Names:
Drug: Placebo
Tablets administered orally
|
| Experimental: 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. |
Drug: Cilofexor
Tablets administered orally
Other Names:
Drug: Placebo
Tablets administered orally
|
| Experimental: 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. |
Drug: Cilofexor
Tablets administered orally
Other Names:
Drug: Placebo
Tablets administered orally
|
| Experimental: 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. |
Drug: Cilofexor
Tablets administered orally
Other Names:
Drug: Placebo
Tablets administered orally
|
| Experimental: 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. |
Drug: Cilofexor
Tablets administered orally
Other Names:
Drug: Placebo
Tablets administered orally
|
| Experimental: Cohort 9: Cilofexor Participants will receive cilofexor up to 300 mg or placebo once daily in the evening on empty stomach. |
Drug: Cilofexor
Tablets administered orally
Other Names:
Drug: Placebo
Tablets administered orally
|
| Experimental: Cohort 10: Cilofexor Participants will receive cilofexor up to 300 mg or placebo once daily in the evening on empty stomach. |
Drug: Cilofexor
Tablets administered orally
Other Names:
Drug: Placebo
Tablets administered orally
|
Outcome Measures
Primary Outcome Measures
- Single-Dose Pharmacokinetic (PK) Parameter: AUClast of Cilofexor [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 [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 [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 [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 [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 [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) [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 [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 [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.
Secondary Outcome Measures
- 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]
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.
- 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]
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.
- 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]
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.
- 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]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 45 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | SeaView Research, Inc | Miami | Florida | United States |
Sponsors and Collaborators
- Gilead Sciences
Investigators
- Study Director: Gilead Study Director, Gilead Sciences
Study Documents (Full-Text)
None provided.More Information
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.
Responsible Party:
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT02654002
Other Study ID Numbers:
- GS-US-402-1851
First Posted:
Jan 13, 2016
Last Update Posted:
Oct 12, 2020
Last Verified:
Sep 1, 2020
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants were enrolled at one study site in the United States. The first participant was screened on 20 January 2016. The last study visit occurred on 14 July 2016. |
|---|---|
| Pre-assignment Detail | 183 participants were screened. No participants were enrolled in Cohorts 9 and 10. |
| Arm/Group Title | 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 | All Placebo |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants in fasted state received cilofexor 10 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 10 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 30 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 30 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 100 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 100 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 300 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 300 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fed state received cilofexor 100 mg tablet, orally, once with food on Day 1 followed by a 5-day washout period then received cilofexor 100 mg tablet, orally, once daily with food from Day 7 to Day 20. | Participants in fed state received cilofexor 50 mg tablet, orally, twice with food on Day 1 followed by a 5-day washout period then received cilofexor 50 mg tablet, orally, twice daily from Day 7 to Day 20. | Participants in fed state received cilofexor 15 mg tablet orally, twice with food on Day 1 followed by a 5-day washout period then received cilofexor 15 mg tablet orally, twice daily from Day 7 to Day 20. | Participants in fed state received cilofexor 10 mg tablet, orally, once with food on Day 1 followed by a 5-day washout period then received cilofexor 10 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state (cohorts 1-4) and fed state (cohorts 5-8) received placebo tablet(s), orally, once or twice on Day 1 followed by a 5-day washout period then received placebo tablet(s), orally, once or twice daily from Day 7 to Day 20. |
| Period Title: Overall Study | |||||||||
| STARTED | 12 | 12 | 12 | 12 | 12 | 12 | 12 | 12 | 24 |
| COMPLETED | 12 | 12 | 12 | 12 | 12 | 11 | 11 | 11 | 24 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 0 |
Baseline Characteristics
| Arm/Group Title | 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 | All Placebo | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants in fasted state received cilofexor 10 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 10 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 30 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 30 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 100 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 100 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 300 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 300 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fed state received cilofexor 100 mg tablet, orally, once with food on Day 1 followed by a 5-day washout period then received cilofexor 100 mg tablet, orally, once daily with food from Day 7 to Day 20. | Participants in fed state received cilofexor 50 mg tablet, orally, twice with food on Day 1 followed by a 5-day washout period then received cilofexor 50 mg tablet, orally, twice daily from Day 7 to Day 20. | Participants in fed state received cilofexor 15 mg tablet orally, twice with food on Day 1 followed by a 5-day washout period then received cilofexor 15 mg tablet orally, twice daily from Day 7 to Day 20. | Participants in fed state received cilofexor 10 mg tablet, orally, once with food on Day 1 followed by a 5-day washout period then received cilofexor 10 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state (cohorts 1-4) and fed state (cohorts 5-8) received placebo tablet(s), orally, once or twice on Day 1 followed by a 5-day washout period then received placebo tablet(s), orally, once or twice daily from Day 7 to Day 20. | Total of all reporting groups |
| Overall Participants | 12 | 12 | 12 | 12 | 12 | 11 | 12 | 11 | 24 | 118 |
| Age (years) [Mean (Standard Deviation) ] | ||||||||||
| Mean (Standard Deviation) [years] |
34
(6.5)
|
35
(8.9)
|
37
(6.1)
|
32
(8.7)
|
40
(4.6)
|
33
(7.4)
|
35
(6.0)
|
35
(7.1)
|
36
(6.7)
|
35
(7.1)
|
| Sex: Female, Male (Count of Participants) | ||||||||||
| Female |
6
50%
|
4
33.3%
|
5
41.7%
|
4
33.3%
|
5
41.7%
|
6
54.5%
|
7
58.3%
|
8
72.7%
|
14
58.3%
|
59
50%
|
| Male |
6
50%
|
8
66.7%
|
7
58.3%
|
8
66.7%
|
7
58.3%
|
5
45.5%
|
5
41.7%
|
3
27.3%
|
10
41.7%
|
59
50%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||||||||
| Hispanic or Latino |
11
91.7%
|
12
100%
|
11
91.7%
|
12
100%
|
12
100%
|
11
100%
|
12
100%
|
11
100%
|
24
100%
|
116
98.3%
|
| Not Hispanic or Latino |
1
8.3%
|
0
0%
|
1
8.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
1.7%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||||||||
| Black |
1
8.3%
|
1
8.3%
|
2
16.7%
|
3
25%
|
2
16.7%
|
2
18.2%
|
1
8.3%
|
2
18.2%
|
2
8.3%
|
16
13.6%
|
| White |
11
91.7%
|
11
91.7%
|
10
83.3%
|
9
75%
|
10
83.3%
|
9
81.8%
|
11
91.7%
|
9
81.8%
|
22
91.7%
|
102
86.4%
|
| Region of Enrollment (participants) [Number] | ||||||||||
| United States |
12
100%
|
12
100%
|
12
100%
|
12
100%
|
12
100%
|
11
100%
|
12
100%
|
11
100%
|
24
100%
|
118
100%
|
Outcome Measures
| Title | Single-Dose Pharmacokinetic (PK) Parameter: AUClast of Cilofexor |
|---|---|
| Description | AUClast is defined as the concentration of drug from time zero to the last quantifiable concentration. |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants in fasted state received cilofexor 10 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 10 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 30 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 30 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 100 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 100 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 300 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 300 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fed state received cilofexor 100 mg tablet, orally, once with food on Day 1 followed by a 5-day washout period then received cilofexor 100 mg tablet, orally, once daily with food from Day 7 to Day 20. | Participants in fed state received cilofexor 50 mg tablet, orally, twice with food on Day 1 followed by a 5-day washout period then received cilofexor 50 mg tablet, orally, twice daily from Day 7 to Day 20. | Participants in fed state received cilofexor 15 mg tablet orally, twice with food on Day 1 followed by a 5-day washout period then received cilofexor 15 mg tablet orally, twice daily from Day 7 to Day 20. | Participants in fed state received cilofexor 10 mg tablet, orally, once with food on Day 1 followed by a 5-day washout period then received cilofexor 10 mg tablet, orally, once daily from Day 7 to Day 20. |
| Measure Participants | 12 | 12 | 12 | 12 | 12 | 11 | 12 | 11 |
| Mean (Standard Deviation) [hours*nanogram/millilitre (h*ng/mL)] |
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)
|
| Title | Single-Dose PK Parameter: AUCinf of Cilofexor |
|---|---|
| Description | AUCinf is defined as the concentration of drug extrapolated to infinite time (area under the plasma concentration versus time curve extrapolated to infinite time). |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the PK Analysis Set were analyzed. |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants in fasted state received cilofexor 10 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 10 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 30 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 30 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 100 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 100 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 300 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 300 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fed state received cilofexor 100 mg tablet, orally, once with food on Day 1 followed by a 5-day washout period then received cilofexor 100 mg tablet, orally, once daily with food from Day 7 to Day 20. | Participants in fed state received cilofexor 50 mg tablet, orally, twice with food on Day 1 followed by a 5-day washout period then received cilofexor 50 mg tablet, orally, twice daily from Day 7 to Day 20. | Participants in fed state received cilofexor 15 mg tablet orally, twice with food on Day 1 followed by a 5-day washout period then received cilofexor 15 mg tablet orally, twice daily from Day 7 to Day 20. | Participants in fed state received cilofexor 10 mg tablet, orally, once with food on Day 1 followed by a 5-day washout period then received cilofexor 10 mg tablet, orally, once daily from Day 7 to Day 20. |
| Measure Participants | 12 | 12 | 12 | 12 | 12 | 11 | 12 | 11 |
| Mean (Standard Deviation) [h*ng/mL] |
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)
|
| Title | Single-Dose PK Parameter: Cmax of Cilofexor |
|---|---|
| Description | Cmax is defined as the maximum observed concentration of drug in plasma. |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the PK Analysis Set were analyzed. |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants in fasted state received cilofexor 10 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 10 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 30 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 30 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 100 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 100 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 300 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 300 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fed state received cilofexor 100 mg tablet, orally, once with food on Day 1 followed by a 5-day washout period then received cilofexor 100 mg tablet, orally, once daily with food from Day 7 to Day 20. | Participants in fed state received cilofexor 50 mg tablet, orally, twice with food on Day 1 followed by a 5-day washout period then received cilofexor 50 mg tablet, orally, twice daily from Day 7 to Day 20. | Participants in fed state received cilofexor 15 mg tablet orally, twice with food on Day 1 followed by a 5-day washout period then received cilofexor 15 mg tablet orally, twice daily from Day 7 to Day 20. | Participants in fed state received cilofexor 10 mg tablet, orally, once with food on Day 1 followed by a 5-day washout period then received cilofexor 10 mg tablet, orally, once daily from Day 7 to Day 20. |
| Measure Participants | 12 | 12 | 12 | 12 | 12 | 11 | 12 | 11 |
| Mean (Standard Deviation) [ng/mL] |
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)
|
| Title | Multiple-Dose PK Parameter: AUCtau of Cilofexor |
|---|---|
| Description | AUCtau is the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval). |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the PK Analysis Set were analyzed. |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants in fasted state received cilofexor 10 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 10 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 30 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 30 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 100 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 100 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 300 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 300 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fed state received cilofexor 100 mg tablet, orally, once with food on Day 1 followed by a 5-day washout period then received cilofexor 100 mg tablet, orally, once daily with food from Day 7 to Day 20. | Participants in fed state received cilofexor 50 mg tablet, orally, twice with food on Day 1 followed by a 5-day washout period then received cilofexor 50 mg tablet, orally, twice daily from Day 7 to Day 20. | Participants in fed state received cilofexor 15 mg tablet orally, twice with food on Day 1 followed by a 5-day washout period then received cilofexor 15 mg tablet orally, twice daily from Day 7 to Day 20. | Participants in fed state received cilofexor 10 mg tablet, orally, once with food on Day 1 followed by a 5-day washout period then received cilofexor 10 mg tablet, orally, once daily from Day 7 to Day 20. |
| Measure Participants | 12 | 12 | 12 | 12 | 12 | 11 | 11 | 11 |
| Mean (Standard Deviation) [h*ng/mL] |
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)
|
| Title | Multiple-Dose PK Parameter: Cmax of Cilofexor |
|---|---|
| Description | Cmax is defined as the maximum observed concentration of drug in plasma. |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the PK Analysis Set with available data were analyzed. |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants in fasted state received cilofexor 10 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 10 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 30 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 30 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 100 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 100 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 300 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 300 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fed state received cilofexor 100 mg tablet, orally, once with food on Day 1 followed by a 5-day washout period then received cilofexor 100 mg tablet, orally, once daily with food from Day 7 to Day 20. | Participants in fed state received cilofexor 50 mg tablet, orally, twice with food on Day 1 followed by a 5-day washout period then received cilofexor 50 mg tablet, orally, twice daily from Day 7 to Day 20. | Participants in fed state received cilofexor 15 mg tablet orally, twice with food on Day 1 followed by a 5-day washout period then received cilofexor 15 mg tablet orally, twice daily from Day 7 to Day 20. | Participants in fed state received cilofexor 10 mg tablet, orally, once with food on Day 1 followed by a 5-day washout period then received cilofexor 10 mg tablet, orally, once daily from Day 7 to Day 20. |
| Measure Participants | 12 | 12 | 12 | 12 | 12 | 11 | 11 | 11 |
| Mean (Standard Deviation) [ng/mL] |
322.2
(136.70)
|
717.5
(235.50)
|
2231.2
(1693.78)
|
2327.9
(1897.48)
|
818.7
(437.28)
|
697.8
(145.60)
|
290.4
(78.71)
|
187.0
(57.10)
|
| Title | Multiple-Dose PK Parameter: Ctau of Cilofexor |
|---|---|
| Description | Ctau is defined as the observed drug concentration at the end of the dosing interval. |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the PK Analysis Set with available data were analyzed. |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants in fasted state received cilofexor 10 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 10 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 30 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 30 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 100 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 100 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 300 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 300 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fed state received cilofexor 100 mg tablet, orally, once with food on Day 1 followed by a 5-day washout period then received cilofexor 100 mg tablet, orally, once daily with food from Day 7 to Day 20. | Participants in fed state received cilofexor 50 mg tablet, orally, twice with food on Day 1 followed by a 5-day washout period then received cilofexor 50 mg tablet, orally, twice daily from Day 7 to Day 20. | Participants in fed state received cilofexor 15 mg tablet orally, twice with food on Day 1 followed by a 5-day washout period then received cilofexor 15 mg tablet orally, twice daily from Day 7 to Day 20. | Participants in fed state received cilofexor 10 mg tablet, orally, once with food on Day 1 followed by a 5-day washout period then received cilofexor 10 mg tablet, orally, once daily from Day 7 to Day 20. |
| Measure Participants | 12 | 12 | 12 | 12 | 12 | 11 | 11 | 11 |
| Mean (Standard Deviation) [ng/mL] |
2.7
(1.53)
|
7.9
(3.97)
|
36.3
(15.44)
|
70.1
(39.46)
|
22.6
(8.44)
|
107.6
(84.58)
|
28.4
(14.13)
|
3.0
(1.54)
|
| Title | Percentage of Participants With at Least One Adverse Event (AE) |
|---|---|
| Description | 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. |
| Time Frame | First dose date up to last dose date (Maximum: 20 days) plus 30 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Safety Analysis Set included all randomized participants who took at least 1 dose of study drug. Participants were grouped according to the treatment they actually received. |
| Arm/Group Title | 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 | All Placebo |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants in fasted state received cilofexor 10 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 10 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 30 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 30 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 100 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 100 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 300 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 300 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fed state received cilofexor 100 mg tablet, orally, once with food on Day 1 followed by a 5-day washout period then received cilofexor 100 mg tablet, orally, once daily with food from Day 7 to Day 20. | Participants in fed state received cilofexor 50 mg tablet, orally, twice with food on Day 1 followed by a 5-day washout period then received cilofexor 50 mg tablet, orally, twice daily from Day 7 to Day 20. | Participants in fed state received cilofexor 15 mg tablet orally, twice with food on Day 1 followed by a 5-day washout period then received cilofexor 15 mg tablet orally, twice daily from Day 7 to Day 20. | Participants in fed state received cilofexor 10 mg tablet, orally, once with food on Day 1 followed by a 5-day washout period then received cilofexor 10 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state (cohorts 1-4) and fed state (cohorts 5-8) received placebo tablet(s), orally, once or twice on Day 1 followed by a 5-day washout period then received placebo tablet(s), orally, once or twice daily from Day 7 to Day 20. |
| Measure Participants | 12 | 12 | 12 | 12 | 12 | 11 | 12 | 11 | 24 |
| Number [percentage of participants] |
33.3
277.5%
|
25.0
208.3%
|
33.3
277.5%
|
25.0
208.3%
|
41.7
347.5%
|
27.3
248.2%
|
75.0
625%
|
18.2
165.5%
|
29.2
121.7%
|
| Title | Percentage of Participants With Clinically Significant 12-Lead Electrocardiogram (ECG) Abnormalities |
|---|---|
| Description | Investigator determined the ECG findings were clinically significant. |
| Time Frame | First dose date up to last dose date (Maximum: 20 days) plus 30 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set were analyzed. Participants were grouped according to the treatment they actually received. |
| Arm/Group Title | 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 | All Placebo |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants in fasted state received cilofexor 10 mg tablet, orally, once on Day 1 followed by a 5-day washout period then receive cilofexor 10 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 30 mg tablet, orally, once on Day 1 followed by a 5-day washout period then receive cilofexor 30 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 100 mg tablet, orally, once on Day 1 followed by a 5-day washout period then receive cilofexor 100 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 300 mg tablet, orally, once on Day 1 followed by a 5-day washout period then receive cilofexor 300 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fed state received cilofexor 100 mg tablet, orally, once with food on Day 1 followed by a 5-day washout period then receive cilofexor 100 mg tablet, orally, once daily with food from Day 7 to Day 20. | Participants in fed state received cilofexor 50 mg tablet, orally, twice with food on Day 1 followed by a 5-day washout period then receive cilofexor 50 mg tablet, orally, twice daily from Day 7 to Day 20. | Participants in fed state received cilofexor 15 mg tablet orally, twice with food on Day 1 followed by a 5-day washout period then receive cilofexor 15 mg tablet orally, twice daily from Day 7 to Day 20. | Participants in fed state received cilofexor 10 mg tablet, orally, once with food on Day 1 followed by a 5-day washout period then receive cilofexor 10 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state (cohorts 1-4) and fed state (cohorts 5-8) received placebo tablet(s), orally, once or twice on Day 1 followed by a 5-day washout period then receive placebo tablet(s), orally, once or twice daily from Day 7 to Day 20. |
| Measure Participants | 12 | 12 | 12 | 12 | 12 | 11 | 12 | 11 | 24 |
| Number [percentage of participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Percentage of Participants With Clinical Laboratory Abnormalities |
|---|---|
| Description | 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. |
| Time Frame | First dose date up to last dose date (Maximum: 20 days) plus 30 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set with available data were analyzed. Participants were grouped according to the treatment they actually received. |
| Arm/Group Title | 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 | All Placebo |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants in fasted state received cilofexor 10 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 10 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 30 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 30 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 100 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 100 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 300 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 300 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fed state received cilofexor 100 mg tablet, orally, once with food on Day 1 followed by a 5-day washout period then received cilofexor 100 mg tablet, orally, once daily with food from Day 7 to Day 20. | Participants in fed state received cilofexor 50 mg tablet, orally, twice with food on Day 1 followed by a 5-day washout period then received cilofexor 50 mg tablet, orally, twice daily from Day 7 to Day 20. | Participants in fed state received cilofexor 15 mg tablet orally, twice with food on Day 1 followed by a 5-day washout period then received cilofexor 15 mg tablet orally, twice daily from Day 7 to Day 20. | Participants in fed state received cilofexor 10 mg tablet, orally, once with food on Day 1 followed by a 5-day washout period then received cilofexor 10 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state (cohorts 1-4) and fed state (cohorts 5-8) received placebo tablet(s), orally, once or twice on Day 1 followed by a 5-day washout period then received placebo tablet(s), orally, once or twice daily from Day 7 to Day 20. |
| Measure Participants | 12 | 12 | 12 | 12 | 12 | 11 | 12 | 11 | 24 |
| Activated Partial Thromboplastin Time: Grade 1 |
0.0
0%
|
8.3
69.2%
|
16.7
139.2%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
| Hemoglobin-Hypo: Grade 1 |
16.7
139.2%
|
25.0
208.3%
|
16.7
139.2%
|
8.3
69.2%
|
16.7
139.2%
|
18.2
165.5%
|
25.0
208.3%
|
27.3
248.2%
|
29.2
121.7%
|
| Hemoglobin-Hypo: Grade 2 |
0.0
0%
|
0.0
0%
|
8.3
69.2%
|
8.3
69.2%
|
8.3
69.2%
|
0.0
0%
|
16.7
139.2%
|
9.1
82.7%
|
8.3
34.6%
|
| Hemoglobin-Hypo: Grade 3 |
0.0
0%
|
0.0
0%
|
0.0
0%
|
8.3
69.2%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
| International Normalized Ratio: Grade 2 |
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
8.3
69.2%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
| Lymphocytes: Grade 1 |
0.0
0%
|
8.3
69.2%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
| Platelets: Grade 2 |
0.0
0%
|
8.3
69.2%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
| Alanine Aminotransferase: Grade 1 |
0.0
0%
|
0.0
0%
|
0.0
0%
|
8.3
69.2%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
9.1
82.7%
|
4.2
17.5%
|
| Alanine Aminotransferase: Grade 2 |
0.0
0%
|
16.7
139.2%
|
0.0
0%
|
0.0
0%
|
8.3
69.2%
|
9.1
82.7%
|
0.0
0%
|
0.0
0%
|
4.2
17.5%
|
| Alanine Aminotransferase: Grade 3 |
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
8.3
69.2%
|
0.0
0%
|
0.0
0%
|
| Aspartate Aminotransferase: Grade 1 |
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
8.3
69.2%
|
9.1
82.7%
|
0.0
0%
|
0.0
0%
|
4.2
17.5%
|
| Aspartate Aminotransferase: Grade 2 |
0.0
0%
|
8.3
69.2%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
8.3
69.2%
|
0.0
0%
|
0.0
0%
|
| Aspartate Aminotransferase: Grade 3 |
0.0
0%
|
8.3
69.2%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
| Aspartate Aminotransferase: Grade 4 |
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
4.2
17.5%
|
| Albumin Corrected Calcium-Hyper: Grade 1 |
0.0
0%
|
0.0
0%
|
0.0
0%
|
8.3
69.2%
|
8.3
69.2%
|
9.1
82.7%
|
8.3
69.2%
|
0.0
0%
|
4.2
17.5%
|
| Gamma-Glutamyltransferase: Grade 1 |
0.0
0%
|
0.0
0%
|
8.3
69.2%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
4.2
17.5%
|
| Gamma-Glutamyltransferase: Grade 2 |
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
8.3
69.2%
|
0.0
0%
|
0.0
0%
|
| Low-Density Lipoprotein: Grade 1 |
8.3
69.2%
|
0.0
0%
|
8.3
69.2%
|
8.3
69.2%
|
25.0
208.3%
|
27.3
248.2%
|
25.0
208.3%
|
18.2
165.5%
|
12.5
52.1%
|
| Low-Density Lipoprotein: Grade 2 |
8.3
69.2%
|
8.3
69.2%
|
8.3
69.2%
|
8.3
69.2%
|
16.7
139.2%
|
0.0
0%
|
8.3
69.2%
|
0.0
0%
|
4.2
17.5%
|
| Phosphate-Hypo: Grade 1 |
0.0
0%
|
8.3
69.2%
|
0.0
0%
|
8.3
69.2%
|
8.3
69.2%
|
0.0
0%
|
8.3
69.2%
|
9.1
82.7%
|
4.2
17.5%
|
| Phosphate-Hypo: Grade 2 |
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
4.2
17.5%
|
| Serum Amylase: Grade 1 |
0.0
0%
|
8.3
69.2%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
| Serum Amylase: Grade 2 |
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
9.1
82.7%
|
4.2
17.5%
|
| Serum Glucose,Fasting-Hyper: Grade 1 |
0.0
0%
|
8.3
69.2%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
| Serum Glucose,Fasting-Hyper:Grade 2 |
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
9.1
82.7%
|
0.0
0%
|
| Serum Glucose,Non-Fasting-Hyper:Grade 1 |
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
58.3
485.8%
|
0.0
0%
|
18.2
151.7%
|
0.0
0%
|
4.2
17.5%
|
| Serum Glucose,Non-Fasting-Hyper:Grade 2 |
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
9.1
82.7%
|
0.0
0%
|
| Serum Glucose,Non-Fasting-Hypo:Grade 1 |
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
8.3
69.2%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
4.2
17.5%
|
| Serum Potassium-Hypo:Grade 1 |
0.0
0%
|
8.3
69.2%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
27.3
248.2%
|
0.0
0%
|
| Serum Sodium-Hyper:Grade 1 |
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
9.1
82.7%
|
0.0
0%
|
| Serum Sodium-Hypo:Grade 1 |
8.3
69.2%
|
25.0
208.3%
|
8.3
69.2%
|
0.0
0%
|
0.0
0%
|
18.2
165.5%
|
50.0
416.7%
|
9.1
82.7%
|
4.2
17.5%
|
| Total Bilirubin-Hyper:Grade 1 |
0.0
0%
|
0.0
0%
|
0.0
0%
|
8.3
69.2%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
9.1
82.7%
|
4.2
17.5%
|
| Total Cholesterol-Hyper:Grade 1 |
16.7
139.2%
|
0.0
0%
|
16.7
139.2%
|
16.7
139.2%
|
25.0
208.3%
|
36.4
330.9%
|
25.0
208.3%
|
9.1
82.7%
|
12.5
52.1%
|
| Total Cholesterol-Hyper:Grade 2 |
8.3
69.2%
|
0.0
0%
|
8.3
69.2%
|
0.0
0%
|
16.7
139.2%
|
0.0
0%
|
8.3
69.2%
|
9.1
82.7%
|
4.2
17.5%
|
| Uric Acid-Hyper:Grade 1 |
0.0
0%
|
0.0
0%
|
8.3
69.2%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
| Uric Acid-Hypo:Grade 1 |
8.3
69.2%
|
16.7
139.2%
|
0.0
0%
|
8.3
69.2%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
| Occult Blood: Grade 1 |
0.0
0%
|
0.0
0%
|
8.3
69.2%
|
0.0
0%
|
8.3
69.2%
|
0.0
0%
|
0.0
0%
|
9.1
82.7%
|
8.3
34.6%
|
| Occult Blood: Grade 2 |
16.7
139.2%
|
8.3
69.2%
|
0.0
0%
|
8.3
69.2%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
9.1
82.7%
|
12.5
52.1%
|
| Occult Blood: Grade 3 |
25.0
208.3%
|
8.3
69.2%
|
8.3
69.2%
|
16.7
139.2%
|
8.3
69.2%
|
18.2
165.5%
|
16.7
139.2%
|
18.2
165.5%
|
8.3
34.6%
|
| Urine Glucose: Grade 1 |
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
9.1
82.7%
|
0.0
0%
|
| Urine Protein: Grade 1 |
0.0
0%
|
8.3
69.2%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
4.2
17.5%
|
| Title | Pharmacodynamic (PD) Parameter: Fibroblast Growth Factor 19 (FGF19) AUC2-12 Ratio |
|---|---|
| Description | 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. |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PD Analysis Set included all randomized participants who received at least 1 dose of study drug and had the necessary baseline and on-study measurement to provide interpretable results for each respective PD parameter. Included participants with available data. |
| Arm/Group Title | Cohort 1: Cilofexor 10 mg | Cohort 2: Cilofexor 30 mg | Cohort 3: Cilofexor 100 mg | Cohort 4: Cilofexor 300 mg | All Fasted Placebo | Cohort 5: Cilofexor 100 mg | Cohort 6: Cilofexor 50 mg | Cohort 7: Cilofexor 15 mg | Cohort 8: Cilofexor 10 mg | All Fed Placebo |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants in fasted state received cilofexor 10 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 10 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 30 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 30 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 100 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 100 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 300 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 300 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state (cohorts 1-4) received placebo tablet(s), orally, once on Day 1 followed by a 5-day washout period then received placebo tablet(s), orally, once daily from Day 7 to Day 20. | Participants in fed state received cilofexor 100 mg tablet, orally, once with food on Day 1 followed by a 5-day washout period then received cilofexor 100 mg tablet, orally, once daily with food from Day 7 to Day 20. | Participants in fed state received cilofexor 50 mg tablet, orally, twice with food on Day 1 followed by a 5-day washout period then received cilofexor 50 mg tablet, orally, twice daily from Day 7 to Day 20. | Participants in fed state received cilofexor 15 mg tablet orally, twice with food on Day 1 followed by a 5-day washout period then received cilofexor 15 mg tablet orally, twice daily from Day 7 to Day 20. | Participants in fed state received cilofexor 10 mg tablet, orally, once with food on Day 1 followed by a 5-day washout period then received cilofexor 10 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fed state (cohorts 5-8) received placebo tablet(s), orally, once or twice on Day 1 followed by a 5-day washout period then received placebo tablet(s), orally, once or twice daily from Day 7 to Day 20. |
| Measure Participants | 12 | 12 | 12 | 12 | 12 | 12 | 11 | 12 | 11 | 12 |
| Day 1/Day -1 |
2.040
|
1.958
|
2.037
|
2.314
|
0.981
|
2.406
|
2.629
|
1.743
|
1.372
|
0.916
|
| Day 20/Day -1 |
2.270
|
2.261
|
2.054
|
2.179
|
1.249
|
1.795
|
2.119
|
1.650
|
1.509
|
0.963
|
| Title | PD Parameter: FGF19 Cmax Ratio |
|---|---|
| Description | 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. |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the PD Analysis Set with available data were analyzed. |
| Arm/Group Title | Cohort 1: Cilofexor 10 mg | Cohort 2: Cilofexor 30 mg | Cohort 3: Cilofexor 100 mg | Cohort 4: Cilofexor 300 mg | All Fasted Placebo | Cohort 5: Cilofexor 100 mg | Cohort 6: Cilofexor 50 mg | Cohort 7: Cilofexor 15 mg | Cohort 8: Cilofexor 10 mg | All Fed Placebo |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants in fasted state received cilofexor 10 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 10 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 30 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 30 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 100 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 100 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 300 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 300 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state (cohorts 1-4) received placebo tablet(s), orally, once on Day 1 followed by a 5-day washout period then received placebo tablet(s), orally, once daily from Day 7 to Day 20. | Participants in fed state received cilofexor 100 mg tablet, orally, once with food on Day 1 followed by a 5-day washout period then received cilofexor 100 mg tablet, orally, once daily with food from Day 7 to Day 20. | Participants in fed state received cilofexor 50 mg tablet, orally, twice with food on Day 1 followed by a 5-day washout period then received cilofexor 50 mg tablet, orally, twice daily from Day 7 to Day 20. | Participants in fed state received cilofexor 15 mg tablet orally, twice with food on Day 1 followed by a 5-day washout period then received cilofexor 15 mg tablet orally, twice daily from Day 7 to Day 20. | Participants in fed state received cilofexor 10 mg tablet, orally, once with food on Day 1 followed by a 5-day washout period then received cilofexor 10 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fed state (cohorts 5-8) received placebo tablet(s), orally, once or twice on Day 1 followed by a 5-day washout period then received placebo tablet(s), orally, once or twice daily from Day 7 to Day 20. |
| Measure Participants | 12 | 12 | 12 | 12 | 12 | 12 | 11 | 12 | 11 | 12 |
| Day 1/Day -1 |
2.217
|
2.084
|
2.259
|
2.679
|
0.982
|
2.793
|
2.973
|
1.961
|
1.689
|
0.929
|
| Day 20/Day -1 |
2.157
|
2.393
|
2.325
|
3.084
|
1.210
|
2.241
|
2.455
|
1.768
|
1.878
|
0.874
|
| Title | PD Parameter: 7alpha-hydroxy-4-cholesten-3-one (C4) AUC2-12 Ratio |
|---|---|
| Description | 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. |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the PD Analysis Set with available data were analyzed. |
| Arm/Group Title | Cohort 1: Cilofexor 10 mg | Cohort 2: Cilofexor 30 mg | Cohort 3: Cilofexor 100 mg | Cohort 4: Cilofexor 300 mg | All Fasted Placebo | Cohort 5: Cilofexor 100 mg | Cohort 6: Cilofexor 50 mg | Cohort 7: Cilofexor 15 mg | Cohort 8: Cilofexor 10 mg | All Fed Placebo |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants in fasted state received cilofexor 10 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 10 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 30 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 30 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 100 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 100 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 300 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 300 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state (cohorts 1-4) received placebo tablet(s), orally, once on Day 1 followed by a 5-day washout period then received placebo tablet(s), orally, once daily from Day 7 to Day 20. | Participants in fed state received cilofexor 100 mg tablet, orally, once with food on Day 1 followed by a 5-day washout period then received cilofexor 100 mg tablet, orally, once daily with food from Day 7 to Day 20. | Participants in fed state received cilofexor 50 mg tablet, orally, twice with food on Day 1 followed by a 5-day washout period then received cilofexor 50 mg tablet, orally, twice daily from Day 7 to Day 20. | Participants in fed state received cilofexor 15 mg tablet orally, twice with food on Day 1 followed by a 5-day washout period then received cilofexor 15 mg tablet orally, twice daily from Day 7 to Day 20. | Participants in fed state received cilofexor 10 mg tablet, orally, once with food on Day 1 followed by a 5-day washout period then received cilofexor 10 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fed state (cohorts 5-8) received placebo tablet(s), orally, once or twice on Day 1 followed by a 5-day washout period then received placebo tablet(s), orally, once or twice daily from Day 7 to Day 20. |
| Measure Participants | 12 | 12 | 12 | 12 | 12 | 12 | 11 | 12 | 11 | 12 |
| Day 1/Day -1 |
0.681
|
0.640
|
0.427
|
0.347
|
1.147
|
0.837
|
0.653
|
0.863
|
1.108
|
1.057
|
| Day 20/Day -1 |
0.661
|
0.382
|
0.495
|
0.325
|
1.213
|
0.621
|
0.173
|
0.624
|
0.974
|
0.843
|
| Title | PD Parameter: C4 Cmin Ratio |
|---|---|
| Description | 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. |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the PD Analysis Set with available data were analyzed. |
| Arm/Group Title | Cohort 1: Cilofexor 10 mg | Cohort 2: Cilofexor 30 mg | Cohort 3: Cilofexor 100 mg | Cohort 4: Cilofexor 300 mg | All Fasted Placebo | Cohort 5: Cilofexor 100 mg | Cohort 6: Cilofexor 50 mg | Cohort 7: Cilofexor 15 mg | Cohort 8: Cilofexor 10 mg | All Fed Placebo |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants in fasted state received cilofexor 10 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 10 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 30 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 30 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 100 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 100 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 300 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 300 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state (cohorts 1-4) received placebo tablet(s), orally, once on Day 1 followed by a 5-day washout period then received placebo tablet(s), orally, once daily from Day 7 to Day 20. | Participants in fed state received cilofexor 100 mg tablet, orally, once with food on Day 1 followed by a 5-day washout period then received cilofexor 100 mg tablet, orally, once daily with food from Day 7 to Day 20. | Participants in fed state received cilofexor 50 mg tablet, orally, twice with food on Day 1 followed by a 5-day washout period then received cilofexor 50 mg tablet, orally, twice daily from Day 7 to Day 20. | Participants in fed state received cilofexor 15 mg tablet orally, twice with food on Day 1 followed by a 5-day washout period then received cilofexor 15 mg tablet orally, twice daily from Day 7 to Day 20. | Participants in fed state received cilofexor 10 mg tablet, orally, once with food on Day 1 followed by a 5-day washout period then received cilofexor 10 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fed state (cohorts 5-8) received placebo tablet(s), orally, once or twice on Day 1 followed by a 5-day washout period then received placebo tablet(s), orally, once or twice daily from Day 7 to Day 20. |
| Measure Participants | 12 | 12 | 12 | 12 | 12 | 12 | 11 | 12 | 11 | 12 |
| Day 1/Day -1 |
0.715
|
0.759
|
0.663
|
0.467
|
1.201
|
0.613
|
0.348
|
0.737
|
0.961
|
1.162
|
| Day 20/Day -1 |
0.822
|
0.456
|
0.624
|
0.432
|
1.262
|
0.440
|
0.116
|
0.508
|
0.862
|
0.983
|
Adverse Events
| Time Frame | First dose date up to last dose date (Maximum: 20 days) plus 30 days | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | The Safety Analysis Set included all randomized participants who took at least 1 dose of study drug. Participants were grouped according to the treatment they actually received. | |||||||||||||||||
| Arm/Group Title | 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 | All Placebo | |||||||||
| Arm/Group Description | Participants in fasted state received cilofexor 10 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 10 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 30 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 30 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 100 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 100 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state received cilofexor 300 mg tablet, orally, once on Day 1 followed by a 5-day washout period then received cilofexor 300 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fed state received cilofexor 100 mg tablet, orally, once with food on Day 1 followed by a 5-day washout period then received cilofexor 100 mg tablet, orally, once daily with food from Day 7 to Day 20. | Participants in fed state received cilofexor 50 mg tablet, orally, twice with food on Day 1 followed by a 5-day washout period then received cilofexor 50 mg tablet, orally, twice daily from Day 7 to Day 20. | Participants in fed state received cilofexor 15 mg tablet orally, twice with food on Day 1 followed by a 5-day washout period then received cilofexor 15 mg tablet orally, twice daily from Day 7 to Day 20. | Participants in fed state received cilofexor 10 mg tablet, orally, once with food on Day 1 followed by a 5-day washout period then received cilofexor 10 mg tablet, orally, once daily from Day 7 to Day 20. | Participants in fasted state (cohorts 1-4) and fed state (cohorts 5-8) received placebo tablet(s), orally, once or twice on Day 1 followed by a 5-day washout period then received placebo tablet(s), orally, once or twice daily from Day 7 to Day 20. | |||||||||
All Cause Mortality |
||||||||||||||||||
| 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 | All Placebo | ||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/11 (0%) | 0/12 (0%) | 0/11 (0%) | 0/24 (0%) | |||||||||
Serious Adverse Events |
||||||||||||||||||
| 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 | All Placebo | ||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/11 (0%) | 0/12 (0%) | 0/11 (0%) | 0/24 (0%) | |||||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||||||
| 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 | All Placebo | ||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/12 (33.3%) | 3/12 (25%) | 4/12 (33.3%) | 3/12 (25%) | 5/12 (41.7%) | 3/11 (27.3%) | 9/12 (75%) | 2/11 (18.2%) | 6/24 (25%) | |||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||
| Anaemia | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 2/12 (16.7%) | 0/11 (0%) | 0/12 (0%) | 0/11 (0%) | 0/24 (0%) | |||||||||
| Iron deficiency anaemia | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 1/12 (8.3%) | 0/12 (0%) | 0/11 (0%) | 1/12 (8.3%) | 0/11 (0%) | 1/24 (4.2%) | |||||||||
| Eye disorders | ||||||||||||||||||
| Ocular discomfort | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/11 (0%) | 0/12 (0%) | 0/11 (0%) | 0/24 (0%) | |||||||||
| Gastrointestinal disorders | ||||||||||||||||||
| Abdominal pain | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/11 (0%) | 1/12 (8.3%) | 0/11 (0%) | 0/24 (0%) | |||||||||
| Constipation | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/11 (0%) | 1/12 (8.3%) | 0/11 (0%) | 0/24 (0%) | |||||||||
| Diarrhoea | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 2/12 (16.7%) | 0/11 (0%) | 1/12 (8.3%) | 0/11 (0%) | 0/24 (0%) | |||||||||
| Dyspepsia | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/11 (0%) | 1/12 (8.3%) | 0/11 (0%) | 0/24 (0%) | |||||||||
| Gastritis | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/11 (0%) | 0/12 (0%) | 0/11 (0%) | 0/24 (0%) | |||||||||
| Nausea | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/11 (0%) | 1/12 (8.3%) | 0/11 (0%) | 0/24 (0%) | |||||||||
| Toothache | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 0/11 (0%) | 0/12 (0%) | 0/11 (0%) | 0/24 (0%) | |||||||||
| Vomiting | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/11 (0%) | 1/12 (8.3%) | 0/11 (0%) | 0/24 (0%) | |||||||||
| Immune system disorders | ||||||||||||||||||
| Hypersensitivity | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/11 (0%) | 0/12 (0%) | 0/11 (0%) | 0/24 (0%) | |||||||||
| Infections and infestations | ||||||||||||||||||
| Conjunctivitis | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/11 (0%) | 0/12 (0%) | 0/11 (0%) | 0/24 (0%) | |||||||||
| Oral herpes | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/11 (0%) | 0/12 (0%) | 0/11 (0%) | 0/24 (0%) | |||||||||
| Rhinitis | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/11 (0%) | 0/12 (0%) | 0/11 (0%) | 0/24 (0%) | |||||||||
| Viral infection | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 0/11 (0%) | 1/12 (8.3%) | 0/11 (0%) | 1/24 (4.2%) | |||||||||
| Viral upper respiratory tract infection | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/11 (0%) | 1/12 (8.3%) | 0/11 (0%) | 0/24 (0%) | |||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||||
| Muscle injury | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/11 (0%) | 0/12 (0%) | 0/11 (0%) | 1/24 (4.2%) | |||||||||
| Investigations | ||||||||||||||||||
| Transaminases increased | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/11 (0%) | 1/12 (8.3%) | 0/11 (0%) | 0/24 (0%) | |||||||||
| Metabolism and nutrition disorders | ||||||||||||||||||
| Diabetes mellitus | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/11 (0%) | 0/12 (0%) | 1/11 (9.1%) | 0/24 (0%) | |||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||
| Back pain | 1/12 (8.3%) | 1/12 (8.3%) | 1/12 (8.3%) | 0/12 (0%) | 1/12 (8.3%) | 1/11 (9.1%) | 0/12 (0%) | 0/11 (0%) | 0/24 (0%) | |||||||||
| Muscle spasms | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/11 (0%) | 1/12 (8.3%) | 0/11 (0%) | 0/24 (0%) | |||||||||
| Tendonitis | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/11 (0%) | 1/12 (8.3%) | 0/11 (0%) | 0/24 (0%) | |||||||||
| Nervous system disorders | ||||||||||||||||||
| Dizziness | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/11 (0%) | 1/12 (8.3%) | 0/11 (0%) | 0/24 (0%) | |||||||||
| Headache | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 2/12 (16.7%) | 1/11 (9.1%) | 5/12 (41.7%) | 0/11 (0%) | 3/24 (12.5%) | |||||||||
| Presyncope | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/11 (0%) | 0/12 (0%) | 0/11 (0%) | 0/24 (0%) | |||||||||
| Sciatica | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/11 (0%) | 0/12 (0%) | 1/11 (9.1%) | 0/24 (0%) | |||||||||
| Renal and urinary disorders | ||||||||||||||||||
| Dysuria | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/11 (0%) | 0/12 (0%) | 0/11 (0%) | 0/24 (0%) | |||||||||
| Reproductive system and breast disorders | ||||||||||||||||||
| Dysfunctional uterine bleeding | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/11 (0%) | 1/12 (8.3%) | 0/11 (0%) | 0/24 (0%) | |||||||||
| Menorrhagia | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/11 (0%) | 0/12 (0%) | 0/11 (0%) | 1/24 (4.2%) | |||||||||
| Vaginal discharge | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/11 (0%) | 0/12 (0%) | 0/11 (0%) | 0/24 (0%) | |||||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||||||
| Dermatitis | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/11 (0%) | 0/12 (0%) | 0/11 (0%) | 1/24 (4.2%) | |||||||||
| Dermatitis contact | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/11 (0%) | 1/12 (8.3%) | 0/11 (0%) | 2/24 (8.3%) | |||||||||
| Ecchymosis | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/11 (9.1%) | 0/12 (0%) | 0/11 (0%) | 0/24 (0%) | |||||||||
| Pruritus generalised | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/11 (0%) | 0/12 (0%) | 0/11 (0%) | 0/24 (0%) | |||||||||
| Rash | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/11 (0%) | 0/12 (0%) | 0/11 (0%) | 0/24 (0%) | |||||||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or The study has been completed at all study sites for at least 2 years
Results Point of Contact
| Name/Title | Gilead Clinical Study Information Center |
|---|---|
| Organization | Gilead Sciences |
| Phone | 1-833-445-3230 (GILEAD-0) |
| GileadClinicalTrials@gilead.com |
Responsible Party:
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT02654002
Other Study ID Numbers:
- GS-US-402-1851
First Posted:
Jan 13, 2016
Last Update Posted:
Oct 12, 2020
Last Verified:
Sep 1, 2020