Trial Outcomes & Findings for Study in Healthy Volunteers to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GS-9674 (Cilofexor), and the Effect of Food on GS-9674 Pharmacokinetics and Pharmacodynamics (NCT NCT02654002)

NCT ID: NCT02654002

Last Updated: 2020-10-12

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

120 participants

Primary outcome timeframe

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

Results posted on

2020-10-12

Participant Flow

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.

183 participants were screened. No participants were enrolled in Cohorts 9 and 10.

Participant milestones

Participant milestones
Measure	Cohort 1: Cilofexor 10 mg 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.	Cohort 2: Cilofexor 30 mg 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.	Cohort 3: Cilofexor 100 mg 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.	Cohort 4: Cilofexor 300 mg 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.	Cohort 5: Cilofexor 100 mg 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.	Cohort 6: Cilofexor 50 mg 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.	Cohort 7: Cilofexor 15 mg 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.	Cohort 8: Cilofexor 10 mg 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.	All Placebo 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.
Overall Study STARTED	12	12	12	12	12	12	12	12	24
Overall Study COMPLETED	12	12	12	12	12	11	11	11	24
Overall Study NOT COMPLETED	0	0	0	0	0	1	1	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1: Cilofexor 10 mg 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.	Cohort 2: Cilofexor 30 mg 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.	Cohort 3: Cilofexor 100 mg 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.	Cohort 4: Cilofexor 300 mg 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.	Cohort 5: Cilofexor 100 mg 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.	Cohort 6: Cilofexor 50 mg 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.	Cohort 7: Cilofexor 15 mg 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.	Cohort 8: Cilofexor 10 mg 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.	All Placebo 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.
Overall Study Adverse Event	0	0	0	0	0	0	1	0	0
Overall Study Withdrew Consent	0	0	0	0	0	1	0	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1: Cilofexor 10 mg n=12 Participants 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.	Cohort 2: Cilofexor 30 mg n=12 Participants 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.	Cohort 3: Cilofexor 100 mg n=12 Participants 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.	Cohort 4: Cilofexor 300 mg n=12 Participants 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.	Cohort 5: Cilofexor 100 mg n=12 Participants 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.	Cohort 6: Cilofexor 50 mg n=11 Participants 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.	Cohort 7: Cilofexor 15 mg n=12 Participants 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.	Cohort 8: Cilofexor 10 mg n=11 Participants 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.	All Placebo n=24 Participants 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 n=118 Participants Total of all reporting groups
Age, Continuous	34 years STANDARD_DEVIATION 6.5 • n=93 Participants	35 years STANDARD_DEVIATION 8.9 • n=4 Participants	37 years STANDARD_DEVIATION 6.1 • n=27 Participants	32 years STANDARD_DEVIATION 8.7 • n=483 Participants	40 years STANDARD_DEVIATION 4.6 • n=36 Participants	33 years STANDARD_DEVIATION 7.4 • n=10 Participants	35 years STANDARD_DEVIATION 6.0 • n=115 Participants	35 years STANDARD_DEVIATION 7.1 • n=40 Participants	36 years STANDARD_DEVIATION 6.7 • n=8 Participants	35 years STANDARD_DEVIATION 7.1 • n=62 Participants
Sex: Female, Male Female	6 Participants n=93 Participants	4 Participants n=4 Participants	5 Participants n=27 Participants	4 Participants n=483 Participants	5 Participants n=36 Participants	6 Participants n=10 Participants	7 Participants n=115 Participants	8 Participants n=40 Participants	14 Participants n=8 Participants	59 Participants n=62 Participants
Sex: Female, Male Male	6 Participants n=93 Participants	8 Participants n=4 Participants	7 Participants n=27 Participants	8 Participants n=483 Participants	7 Participants n=36 Participants	5 Participants n=10 Participants	5 Participants n=115 Participants	3 Participants n=40 Participants	10 Participants n=8 Participants	59 Participants n=62 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	11 Participants n=93 Participants	12 Participants n=4 Participants	11 Participants n=27 Participants	12 Participants n=483 Participants	12 Participants n=36 Participants	11 Participants n=10 Participants	12 Participants n=115 Participants	11 Participants n=40 Participants	24 Participants n=8 Participants	116 Participants n=62 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=40 Participants	0 Participants n=8 Participants	2 Participants n=62 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=40 Participants	0 Participants n=8 Participants	0 Participants n=62 Participants
Race/Ethnicity, Customized Race · Black	1 Participants n=93 Participants	1 Participants n=4 Participants	2 Participants n=27 Participants	3 Participants n=483 Participants	2 Participants n=36 Participants	2 Participants n=10 Participants	1 Participants n=115 Participants	2 Participants n=40 Participants	2 Participants n=8 Participants	16 Participants n=62 Participants
Race/Ethnicity, Customized Race · White	11 Participants n=93 Participants	11 Participants n=4 Participants	10 Participants n=27 Participants	9 Participants n=483 Participants	10 Participants n=36 Participants	9 Participants n=10 Participants	11 Participants n=115 Participants	9 Participants n=40 Participants	22 Participants n=8 Participants	102 Participants n=62 Participants
Region of Enrollment United States	12 participants n=93 Participants	12 participants n=4 Participants	12 participants n=27 Participants	12 participants n=483 Participants	12 participants n=36 Participants	11 participants n=10 Participants	12 participants n=115 Participants	11 participants n=40 Participants	24 participants n=8 Participants	118 participants n=62 Participants

PRIMARY outcome

Timeframe: 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

Population: 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.

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

Outcome measures

Outcome measures
Measure	Cohort 5: Cilofexor 100 mg n=11 Participants 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.	Cohort 6: Cilofexor 50 mg n=12 Participants 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.	Cohort 7: Cilofexor 15 mg n=11 Participants 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.	Cohort 1: Cilofexor 10 mg n=12 Participants 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.	Cohort 2: Cilofexor 30 mg n=12 Participants 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.	Cohort 3: Cilofexor 100 mg n=12 Participants 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.	Cohort 4: Cilofexor 300 mg n=12 Participants 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.	Cohort 5: Cilofexor 100 mg n=12 Participants 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.	All Placebo 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 Fed Placebo 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.
Single-Dose Pharmacokinetic (PK) Parameter: AUClast of Cilofexor	3091.4 hoursnanogram/millilitre (hng/mL) Standard Deviation 752.66	1301.9 hoursnanogram/millilitre (hng/mL) Standard Deviation 388.51	905.9 hoursnanogram/millilitre (hng/mL) Standard Deviation 210.24	1236.0 hoursnanogram/millilitre (hng/mL) Standard Deviation 384.65	2450.6 hoursnanogram/millilitre (hng/mL) Standard Deviation 921.70	7712.1 hoursnanogram/millilitre (hng/mL) Standard Deviation 7270.76	12458.8 hoursnanogram/millilitre (hng/mL) Standard Deviation 4223.12	4979.5 hoursnanogram/millilitre (hng/mL) Standard Deviation 2039.07	—	—

PRIMARY outcome

Timeframe: 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

Population: Participants in the PK Analysis Set were analyzed.

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

Outcome measures

Outcome measures
Measure	Cohort 5: Cilofexor 100 mg n=11 Participants 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.	Cohort 6: Cilofexor 50 mg n=12 Participants 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.	Cohort 7: Cilofexor 15 mg n=11 Participants 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.	Cohort 1: Cilofexor 10 mg n=12 Participants 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.	Cohort 2: Cilofexor 30 mg n=12 Participants 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.	Cohort 3: Cilofexor 100 mg n=12 Participants 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.	Cohort 4: Cilofexor 300 mg n=12 Participants 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.	Cohort 5: Cilofexor 100 mg n=12 Participants 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.	All Placebo 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 Fed Placebo 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.
Single-Dose PK Parameter: AUCinf of Cilofexor	3559.2 h*ng/mL Standard Deviation 1092.73	1409.3 h*ng/mL Standard Deviation 428.33	924.0 h*ng/mL Standard Deviation 216.60	1255.9 h*ng/mL Standard Deviation 382.37	2473.4 h*ng/mL Standard Deviation 920.85	7743.7 h*ng/mL Standard Deviation 7273.50	12495.7 h*ng/mL Standard Deviation 4230.00	5016.7 h*ng/mL Standard Deviation 2022.94	—	—

PRIMARY outcome

Timeframe: 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

Population: Participants in the PK Analysis Set were analyzed.

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

Outcome measures

Outcome measures
Measure	Cohort 5: Cilofexor 100 mg n=11 Participants 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.	Cohort 6: Cilofexor 50 mg n=12 Participants 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.	Cohort 7: Cilofexor 15 mg n=11 Participants 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.	Cohort 1: Cilofexor 10 mg n=12 Participants 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.	Cohort 2: Cilofexor 30 mg n=12 Participants 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.	Cohort 3: Cilofexor 100 mg n=12 Participants 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.	Cohort 4: Cilofexor 300 mg n=12 Participants 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.	Cohort 5: Cilofexor 100 mg n=12 Participants 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.	All Placebo 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 Fed Placebo 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.
Single-Dose PK Parameter: Cmax of Cilofexor	665.9 ng/mL Standard Deviation 152.30	340.2 ng/mL Standard Deviation 124.44	209.8 ng/mL Standard Deviation 63.24	304.2 ng/mL Standard Deviation 126.66	580.2 ng/mL Standard Deviation 283.79	2592.3 ng/mL Standard Deviation 3059.31	3055.5 ng/mL Standard Deviation 2022.27	927.6 ng/mL Standard Deviation 540.94	—	—

PRIMARY outcome

Timeframe: 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

Population: Participants in the PK Analysis Set were analyzed.

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

Outcome measures

Outcome measures
Measure	Cohort 5: Cilofexor 100 mg n=11 Participants 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.	Cohort 6: Cilofexor 50 mg n=11 Participants 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.	Cohort 7: Cilofexor 15 mg n=11 Participants 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.	Cohort 1: Cilofexor 10 mg n=12 Participants 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.	Cohort 2: Cilofexor 30 mg n=12 Participants 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.	Cohort 3: Cilofexor 100 mg n=12 Participants 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.	Cohort 4: Cilofexor 300 mg n=12 Participants 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.	Cohort 5: Cilofexor 100 mg n=12 Participants 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.	All Placebo 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 Fed Placebo 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.
Multiple-Dose PK Parameter: AUCtau of Cilofexor	3698.3 h*ng/mL Standard Deviation 837.91	1293.5 h*ng/mL Standard Deviation 250.95	848.2 h*ng/mL Standard Deviation 213.82	1284.9 h*ng/mL Standard Deviation 460.35	2891.0 h*ng/mL Standard Deviation 680.10	6719.4 h*ng/mL Standard Deviation 3980.90	8486.0 h*ng/mL Standard Deviation 4139.86	4182.7 h*ng/mL Standard Deviation 1956.03	—	—

PRIMARY outcome

Timeframe: 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

Population: Participants in the PK Analysis Set with available data were analyzed.

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

Outcome measures

Outcome measures
Measure	Cohort 5: Cilofexor 100 mg n=11 Participants 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.	Cohort 6: Cilofexor 50 mg n=11 Participants 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.	Cohort 7: Cilofexor 15 mg n=11 Participants 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.	Cohort 1: Cilofexor 10 mg n=12 Participants 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.	Cohort 2: Cilofexor 30 mg n=12 Participants 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.	Cohort 3: Cilofexor 100 mg n=12 Participants 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.	Cohort 4: Cilofexor 300 mg n=12 Participants 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.	Cohort 5: Cilofexor 100 mg n=12 Participants 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.	All Placebo 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 Fed Placebo 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.
Multiple-Dose PK Parameter: Cmax of Cilofexor	697.8 ng/mL Standard Deviation 145.60	290.4 ng/mL Standard Deviation 78.71	187.0 ng/mL Standard Deviation 57.10	322.2 ng/mL Standard Deviation 136.70	717.5 ng/mL Standard Deviation 235.50	2231.2 ng/mL Standard Deviation 1693.78	2327.9 ng/mL Standard Deviation 1897.48	818.7 ng/mL Standard Deviation 437.28	—	—

PRIMARY outcome

Timeframe: 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

Population: Participants in the PK Analysis Set with available data were analyzed.

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

Outcome measures

Outcome measures
Measure	Cohort 5: Cilofexor 100 mg n=11 Participants 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.	Cohort 6: Cilofexor 50 mg n=11 Participants 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.	Cohort 7: Cilofexor 15 mg n=11 Participants 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.	Cohort 1: Cilofexor 10 mg n=12 Participants 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.	Cohort 2: Cilofexor 30 mg n=12 Participants 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.	Cohort 3: Cilofexor 100 mg n=12 Participants 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.	Cohort 4: Cilofexor 300 mg n=12 Participants 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.	Cohort 5: Cilofexor 100 mg n=12 Participants 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.	All Placebo 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 Fed Placebo 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.
Multiple-Dose PK Parameter: Ctau of Cilofexor	107.6 ng/mL Standard Deviation 84.58	28.4 ng/mL Standard Deviation 14.13	3.0 ng/mL Standard Deviation 1.54	2.7 ng/mL Standard Deviation 1.53	7.9 ng/mL Standard Deviation 3.97	36.3 ng/mL Standard Deviation 15.44	70.1 ng/mL Standard Deviation 39.46	22.6 ng/mL Standard Deviation 8.44	—	—

PRIMARY outcome

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

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Cohort 5: Cilofexor 100 mg n=11 Participants 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.	Cohort 6: Cilofexor 50 mg n=12 Participants 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.	Cohort 7: Cilofexor 15 mg n=11 Participants 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.	Cohort 1: Cilofexor 10 mg n=12 Participants 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.	Cohort 2: Cilofexor 30 mg n=12 Participants 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.	Cohort 3: Cilofexor 100 mg n=12 Participants 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.	Cohort 4: Cilofexor 300 mg n=12 Participants 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.	Cohort 5: Cilofexor 100 mg n=12 Participants 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.	All Placebo n=24 Participants 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 Fed Placebo 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.
Percentage of Participants With at Least One Adverse Event (AE)	27.3 percentage of participants	75.0 percentage of participants	18.2 percentage of participants	33.3 percentage of participants	25.0 percentage of participants	33.3 percentage of participants	25.0 percentage of participants	41.7 percentage of participants	29.2 percentage of participants	—

PRIMARY outcome

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

Population: Participants in the Safety Analysis Set were analyzed. Participants were grouped according to the treatment they actually received.

Investigator determined the ECG findings were clinically significant.

Outcome measures

Outcome measures
Measure	Cohort 5: Cilofexor 100 mg n=11 Participants 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.	Cohort 6: Cilofexor 50 mg n=12 Participants 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.	Cohort 7: Cilofexor 15 mg n=11 Participants 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.	Cohort 1: Cilofexor 10 mg n=12 Participants 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.	Cohort 2: Cilofexor 30 mg n=12 Participants 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.	Cohort 3: Cilofexor 100 mg n=12 Participants 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.	Cohort 4: Cilofexor 300 mg n=12 Participants 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.	Cohort 5: Cilofexor 100 mg n=12 Participants 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.	All Placebo n=24 Participants 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 Fed Placebo 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.
Percentage of Participants With Clinically Significant 12-Lead Electrocardiogram (ECG) Abnormalities	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	—

PRIMARY outcome

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

Population: Participants in the Safety Analysis Set with available data were analyzed. Participants were grouped according to the treatment they actually received.

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.

Outcome measures

Outcome measures
Measure	Cohort 5: Cilofexor 100 mg n=11 Participants 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.	Cohort 6: Cilofexor 50 mg n=12 Participants 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.	Cohort 7: Cilofexor 15 mg n=11 Participants 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.	Cohort 1: Cilofexor 10 mg n=12 Participants 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.	Cohort 2: Cilofexor 30 mg n=12 Participants 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.	Cohort 3: Cilofexor 100 mg n=12 Participants 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.	Cohort 4: Cilofexor 300 mg n=12 Participants 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.	Cohort 5: Cilofexor 100 mg n=12 Participants 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.	All Placebo n=24 Participants 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 Fed Placebo 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.
Percentage of Participants With Clinical Laboratory Abnormalities Hemoglobin-Hypo: Grade 1	18.2 percentage of participants	25.0 percentage of participants	27.3 percentage of participants	16.7 percentage of participants	25.0 percentage of participants	16.7 percentage of participants	8.3 percentage of participants	16.7 percentage of participants	29.2 percentage of participants	—
Percentage of Participants With Clinical Laboratory Abnormalities Hemoglobin-Hypo: Grade 2	0.0 percentage of participants	16.7 percentage of participants	9.1 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	8.3 percentage of participants	8.3 percentage of participants	8.3 percentage of participants	8.3 percentage of participants	—
Percentage of Participants With Clinical Laboratory Abnormalities Alanine Aminotransferase: Grade 2	9.1 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	16.7 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	8.3 percentage of participants	4.2 percentage of participants	—
Percentage of Participants With Clinical Laboratory Abnormalities Aspartate Aminotransferase: Grade 3	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	8.3 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	—
Percentage of Participants With Clinical Laboratory Abnormalities Aspartate Aminotransferase: Grade 4	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	4.2 percentage of participants	—
Percentage of Participants With Clinical Laboratory Abnormalities Low-Density Lipoprotein: Grade 2	0.0 percentage of participants	8.3 percentage of participants	0.0 percentage of participants	8.3 percentage of participants	8.3 percentage of participants	8.3 percentage of participants	8.3 percentage of participants	16.7 percentage of participants	4.2 percentage of participants	—
Percentage of Participants With Clinical Laboratory Abnormalities Serum Amylase: Grade 2	0.0 percentage of participants	0.0 percentage of participants	9.1 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	4.2 percentage of participants	—
Percentage of Participants With Clinical Laboratory Abnormalities Serum Glucose,Fasting-Hyper: Grade 1	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	8.3 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	—
Percentage of Participants With Clinical Laboratory Abnormalities Total Cholesterol-Hyper:Grade 1	36.4 percentage of participants	25.0 percentage of participants	9.1 percentage of participants	16.7 percentage of participants	0.0 percentage of participants	16.7 percentage of participants	16.7 percentage of participants	25.0 percentage of participants	12.5 percentage of participants	—
Percentage of Participants With Clinical Laboratory Abnormalities Uric Acid-Hyper:Grade 1	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	8.3 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	—
Percentage of Participants With Clinical Laboratory Abnormalities Uric Acid-Hypo:Grade 1	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	8.3 percentage of participants	16.7 percentage of participants	0.0 percentage of participants	8.3 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	—
Percentage of Participants With Clinical Laboratory Abnormalities Occult Blood: Grade 1	0.0 percentage of participants	0.0 percentage of participants	9.1 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	8.3 percentage of participants	0.0 percentage of participants	8.3 percentage of participants	8.3 percentage of participants	—
Percentage of Participants With Clinical Laboratory Abnormalities Occult Blood: Grade 2	0.0 percentage of participants	0.0 percentage of participants	9.1 percentage of participants	16.7 percentage of participants	8.3 percentage of participants	0.0 percentage of participants	8.3 percentage of participants	0.0 percentage of participants	12.5 percentage of participants	—
Percentage of Participants With Clinical Laboratory Abnormalities Occult Blood: Grade 3	18.2 percentage of participants	16.7 percentage of participants	18.2 percentage of participants	25.0 percentage of participants	8.3 percentage of participants	8.3 percentage of participants	16.7 percentage of participants	8.3 percentage of participants	8.3 percentage of participants	—
Percentage of Participants With Clinical Laboratory Abnormalities Urine Glucose: Grade 1	0.0 percentage of participants	0.0 percentage of participants	9.1 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	—
Percentage of Participants With Clinical Laboratory Abnormalities Serum Glucose,Non-Fasting-Hyper:Grade 1	0.0 percentage of participants	18.2 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	58.3 percentage of participants	4.2 percentage of participants	—
Percentage of Participants With Clinical Laboratory Abnormalities Hemoglobin-Hypo: Grade 3	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	8.3 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	—
Percentage of Participants With Clinical Laboratory Abnormalities Activated Partial Thromboplastin Time: Grade 1	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	8.3 percentage of participants	16.7 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	—
Percentage of Participants With Clinical Laboratory Abnormalities International Normalized Ratio: Grade 2	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	8.3 percentage of participants	0.0 percentage of participants	—
Percentage of Participants With Clinical Laboratory Abnormalities Lymphocytes: Grade 1	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	8.3 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	—
Percentage of Participants With Clinical Laboratory Abnormalities Platelets: Grade 2	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	8.3 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	—
Percentage of Participants With Clinical Laboratory Abnormalities Alanine Aminotransferase: Grade 1	0.0 percentage of participants	0.0 percentage of participants	9.1 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	8.3 percentage of participants	0.0 percentage of participants	4.2 percentage of participants	—
Percentage of Participants With Clinical Laboratory Abnormalities Alanine Aminotransferase: Grade 3	0.0 percentage of participants	8.3 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	—
Percentage of Participants With Clinical Laboratory Abnormalities Aspartate Aminotransferase: Grade 1	9.1 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	8.3 percentage of participants	4.2 percentage of participants	—
Percentage of Participants With Clinical Laboratory Abnormalities Aspartate Aminotransferase: Grade 2	0.0 percentage of participants	8.3 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	8.3 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	—
Percentage of Participants With Clinical Laboratory Abnormalities Albumin Corrected Calcium-Hyper: Grade 1	9.1 percentage of participants	8.3 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	8.3 percentage of participants	8.3 percentage of participants	4.2 percentage of participants	—
Percentage of Participants With Clinical Laboratory Abnormalities Gamma-Glutamyltransferase: Grade 1	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	8.3 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	4.2 percentage of participants	—
Percentage of Participants With Clinical Laboratory Abnormalities Gamma-Glutamyltransferase: Grade 2	0.0 percentage of participants	8.3 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	—
Percentage of Participants With Clinical Laboratory Abnormalities Low-Density Lipoprotein: Grade 1	27.3 percentage of participants	25.0 percentage of participants	18.2 percentage of participants	8.3 percentage of participants	0.0 percentage of participants	8.3 percentage of participants	8.3 percentage of participants	25.0 percentage of participants	12.5 percentage of participants	—
Percentage of Participants With Clinical Laboratory Abnormalities Phosphate-Hypo: Grade 1	0.0 percentage of participants	8.3 percentage of participants	9.1 percentage of participants	0.0 percentage of participants	8.3 percentage of participants	0.0 percentage of participants	8.3 percentage of participants	8.3 percentage of participants	4.2 percentage of participants	—
Percentage of Participants With Clinical Laboratory Abnormalities Phosphate-Hypo: Grade 2	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	4.2 percentage of participants	—
Percentage of Participants With Clinical Laboratory Abnormalities Serum Amylase: Grade 1	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	8.3 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	—
Percentage of Participants With Clinical Laboratory Abnormalities Serum Glucose,Fasting-Hyper:Grade 2	0.0 percentage of participants	0.0 percentage of participants	9.1 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	—
Percentage of Participants With Clinical Laboratory Abnormalities Serum Glucose,Non-Fasting-Hyper:Grade 2	0.0 percentage of participants	0.0 percentage of participants	9.1 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	—
Percentage of Participants With Clinical Laboratory Abnormalities Serum Glucose,Non-Fasting-Hypo:Grade 1	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	8.3 percentage of participants	4.2 percentage of participants	—
Percentage of Participants With Clinical Laboratory Abnormalities Serum Potassium-Hypo:Grade 1	0.0 percentage of participants	0.0 percentage of participants	27.3 percentage of participants	0.0 percentage of participants	8.3 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	—
Percentage of Participants With Clinical Laboratory Abnormalities Serum Sodium-Hyper:Grade 1	0.0 percentage of participants	0.0 percentage of participants	9.1 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	—
Percentage of Participants With Clinical Laboratory Abnormalities Serum Sodium-Hypo:Grade 1	18.2 percentage of participants	50.0 percentage of participants	9.1 percentage of participants	8.3 percentage of participants	25.0 percentage of participants	8.3 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	4.2 percentage of participants	—
Percentage of Participants With Clinical Laboratory Abnormalities Total Bilirubin-Hyper:Grade 1	0.0 percentage of participants	0.0 percentage of participants	9.1 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	8.3 percentage of participants	0.0 percentage of participants	4.2 percentage of participants	—
Percentage of Participants With Clinical Laboratory Abnormalities Total Cholesterol-Hyper:Grade 2	0.0 percentage of participants	8.3 percentage of participants	9.1 percentage of participants	8.3 percentage of participants	0.0 percentage of participants	8.3 percentage of participants	0.0 percentage of participants	16.7 percentage of participants	4.2 percentage of participants	—
Percentage of Participants With Clinical Laboratory Abnormalities Urine Protein: Grade 1	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	8.3 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	4.2 percentage of participants	—

SECONDARY outcome

Timeframe: 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

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Cohort 5: Cilofexor 100 mg n=12 Participants 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.	Cohort 6: Cilofexor 50 mg n=11 Participants 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.	Cohort 7: Cilofexor 15 mg n=12 Participants 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.	Cohort 1: Cilofexor 10 mg n=12 Participants 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.	Cohort 2: Cilofexor 30 mg n=12 Participants 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.	Cohort 3: Cilofexor 100 mg n=12 Participants 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.	Cohort 4: Cilofexor 300 mg n=12 Participants 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.	Cohort 5: Cilofexor 100 mg n=12 Participants 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.	All Placebo n=11 Participants 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 Fed Placebo n=12 Participants 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.
Pharmacodynamic (PD) Parameter: Fibroblast Growth Factor 19 (FGF19) AUC2-12 Ratio Day 1/Day -1	2.406 ratio Interval 2.196 to 2.637	2.629 ratio Interval 2.369 to 2.917	1.743 ratio Interval 1.463 to 2.076	2.040 ratio Interval 1.571 to 2.65	1.958 ratio Interval 1.478 to 2.594	2.037 ratio Interval 1.699 to 2.442	2.314 ratio Interval 1.958 to 2.735	0.981 ratio Interval 0.777 to 1.24	1.372 ratio Interval 1.132 to 1.663	0.916 ratio Interval 0.799 to 1.05
Pharmacodynamic (PD) Parameter: Fibroblast Growth Factor 19 (FGF19) AUC2-12 Ratio Day 20/Day -1	1.795 ratio Interval 1.544 to 2.086	2.119 ratio Interval 1.728 to 2.598	1.650 ratio Interval 1.301 to 2.093	2.270 ratio Interval 1.5 to 3.435	2.261 ratio Interval 1.782 to 2.868	2.054 ratio Interval 1.727 to 2.442	2.179 ratio Interval 1.632 to 2.911	1.249 ratio Interval 0.929 to 1.681	1.509 ratio Interval 1.325 to 1.719	0.963 ratio Interval 0.762 to 1.216

SECONDARY outcome

Population: Participants in the PD Analysis Set with available data were analyzed.

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.

Outcome measures

Outcome measures
Measure	Cohort 5: Cilofexor 100 mg n=12 Participants 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.	Cohort 6: Cilofexor 50 mg n=11 Participants 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.	Cohort 7: Cilofexor 15 mg n=12 Participants 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.	Cohort 1: Cilofexor 10 mg n=12 Participants 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.	Cohort 2: Cilofexor 30 mg n=12 Participants 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.	Cohort 3: Cilofexor 100 mg n=12 Participants 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.	Cohort 4: Cilofexor 300 mg n=12 Participants 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.	Cohort 5: Cilofexor 100 mg n=12 Participants 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.	All Placebo n=11 Participants 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 Fed Placebo n=12 Participants 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.
PD Parameter: FGF19 Cmax Ratio Day 1/Day -1	2.793 ratio Interval 2.264 to 3.446	2.973 ratio Interval 2.578 to 3.428	1.961 ratio Interval 1.588 to 2.422	2.217 ratio Interval 1.667 to 2.949	2.084 ratio Interval 1.468 to 2.957	2.259 ratio Interval 1.742 to 2.93	2.679 ratio Interval 2.113 to 3.398	0.982 ratio Interval 0.759 to 1.272	1.689 ratio Interval 1.354 to 2.106	0.929 ratio Interval 0.81 to 1.065
PD Parameter: FGF19 Cmax Ratio Day 20/Day -1	2.241 ratio Interval 1.85 to 2.713	2.455 ratio Interval 1.964 to 3.069	1.768 ratio Interval 1.27 to 2.462	2.157 ratio Interval 1.345 to 3.46	2.393 ratio Interval 1.77 to 3.235	2.325 ratio Interval 1.804 to 2.996	3.084 ratio Interval 2.194 to 4.334	1.210 ratio Interval 0.91 to 1.608	1.878 ratio Interval 1.527 to 2.31	0.874 ratio Interval 0.68 to 1.123

SECONDARY outcome

Population: Participants in the PD Analysis Set with available data were analyzed.

Outcome measures

Outcome measures
Measure	Cohort 5: Cilofexor 100 mg n=12 Participants 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.	Cohort 6: Cilofexor 50 mg n=11 Participants 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.	Cohort 7: Cilofexor 15 mg n=12 Participants 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.	Cohort 1: Cilofexor 10 mg n=12 Participants 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.	Cohort 2: Cilofexor 30 mg n=12 Participants 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.	Cohort 3: Cilofexor 100 mg n=12 Participants 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.	Cohort 4: Cilofexor 300 mg n=12 Participants 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.	Cohort 5: Cilofexor 100 mg n=12 Participants 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.	All Placebo n=11 Participants 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 Fed Placebo n=12 Participants 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.
PD Parameter: 7alpha-hydroxy-4-cholesten-3-one (C4) AUC2-12 Ratio Day 1/Day -1	0.837 ratio Interval 0.629 to 1.114	0.653 ratio Interval 0.581 to 0.735	0.863 ratio Interval 0.747 to 0.997	0.681 ratio Interval 0.431 to 1.077	0.640 ratio Interval 0.516 to 0.794	0.427 ratio Interval 0.34 to 0.537	0.347 ratio Interval 0.278 to 0.433	1.147 ratio Interval 0.921 to 1.429	1.108 ratio Interval 0.828 to 1.483	1.057 ratio Interval 0.893 to 1.252
PD Parameter: 7alpha-hydroxy-4-cholesten-3-one (C4) AUC2-12 Ratio Day 20/Day -1	0.621 ratio Interval 0.414 to 0.933	0.173 ratio Interval 0.109 to 0.275	0.624 ratio Interval 0.472 to 0.825	0.661 ratio Interval 0.456 to 0.959	0.382 ratio Interval 0.277 to 0.525	0.495 ratio Interval 0.348 to 0.704	0.325 ratio Interval 0.223 to 0.474	1.213 ratio Interval 0.828 to 1.777	0.974 ratio Interval 0.677 to 1.402	0.843 ratio Interval 0.681 to 1.043

SECONDARY outcome

Population: Participants in the PD Analysis Set with available data were analyzed.

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.