Trial Outcomes & Findings for Pharmacokinetics and Pharmacodynamics of Cilofexor in Adults With Normal and Impaired Hepatic Function (NCT NCT02808312)
NCT ID: NCT02808312
Last Updated: 2021-01-07
Results Overview
AUClast is defined as the concentration of drug from time zero to the last observable concentration.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
57 participants
Primary outcome timeframe
≤ 5 minutes predose, and 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 postdose on Day 1
Results posted on
2021-01-07
Participant Flow
Participants were enrolled at study sites in the United States (US) and New Zealand. The first participant was screened on 13 July 2016. The last study visit occurred on 16 October 2018.
In the control groups (normal hepatic function), each participant was matched for age, gender, race, and body mass index with a participant in the hepatic impairment group. 17 total unique participants with normal hepatic function were enrolled in Cohort 1 (N = 10) and Cohort 2 (N = 7). 5 participants with normal hepatic function from Cohort 1 also served as matched controls in Cohort 2.
Participant milestones
| Measure |
Cohort 1: Mild Hepatic Impairment
Participants with mild hepatic impairment received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 2: Moderate Hepatic Impairment
Participants with moderate hepatic impairment received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 1 & 2: Normal Hepatic Function
Matched normal hepatic function participants to mild or moderate hepatic impairment participants received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 3: Severe Hepatic Impairment
Participants with severe hepatic impairment received a single oral dose of cilofexor 10 mg (1 x 10 mg tablet) in a fed state, on Day 1.
|
Cohort 3: Normal Hepatic Function
Matched normal hepatic function participants to severe hepatic impairment participants, received a single oral dose of cilofexor 10 mg (1 x 10 mg tablet) in a fed state, on Day 1.
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
10
|
10
|
17
|
10
|
10
|
|
Overall Study
COMPLETED
|
10
|
10
|
16
|
10
|
10
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
1
|
0
|
0
|
Reasons for withdrawal
| Measure |
Cohort 1: Mild Hepatic Impairment
Participants with mild hepatic impairment received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 2: Moderate Hepatic Impairment
Participants with moderate hepatic impairment received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 1 & 2: Normal Hepatic Function
Matched normal hepatic function participants to mild or moderate hepatic impairment participants received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 3: Severe Hepatic Impairment
Participants with severe hepatic impairment received a single oral dose of cilofexor 10 mg (1 x 10 mg tablet) in a fed state, on Day 1.
|
Cohort 3: Normal Hepatic Function
Matched normal hepatic function participants to severe hepatic impairment participants, received a single oral dose of cilofexor 10 mg (1 x 10 mg tablet) in a fed state, on Day 1.
|
|---|---|---|---|---|---|
|
Overall Study
Enrolled but Never Treated
|
0
|
0
|
1
|
0
|
0
|
Baseline Characteristics
Pharmacokinetics and Pharmacodynamics of Cilofexor in Adults With Normal and Impaired Hepatic Function
Baseline characteristics by cohort
| Measure |
Cohort 1: Mild Hepatic Impairment
n=10 Participants
Participants with mild hepatic impairment received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 2: Moderate Hepatic Impairment
n=10 Participants
Participants with moderate hepatic impairment received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 1 & 2: Normal Hepatic Function
n=16 Participants
Matched normal hepatic function participants to mild or moderate hepatic impairment participants, received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 3: Severe Hepatic Impairment
n=10 Participants
Participants with severe hepatic impairment received a single oral dose of cilofexor 10 mg (1 x 10 mg tablet) in a fed state, on Day 1.
|
Cohort 3: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants, received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets ) or 10 mg (1 x 10 mg tablet) in a fed state, on Day 1.
|
Total
n=56 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Continuous
|
54 years
STANDARD_DEVIATION 10.1 • n=5 Participants
|
57 years
STANDARD_DEVIATION 8.9 • n=7 Participants
|
55 years
STANDARD_DEVIATION 7.6 • n=5 Participants
|
54 years
STANDARD_DEVIATION 9.5 • n=4 Participants
|
52 years
STANDARD_DEVIATION 8.4 • n=21 Participants
|
54.45 years
STANDARD_DEVIATION 8.67 • n=10 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
16 Participants
n=10 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
7 Participants
n=21 Participants
|
40 Participants
n=10 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
25 Participants
n=10 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
6 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
31 Participants
n=10 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
2 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
3 Participants
n=10 Participants
|
|
Race (NIH/OMB)
White
|
8 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
9 Participants
n=21 Participants
|
51 Participants
n=10 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
|
Region of Enrollment
New Zealand
|
2 participants
n=5 Participants
|
1 participants
n=7 Participants
|
3 participants
n=5 Participants
|
1 participants
n=4 Participants
|
1 participants
n=21 Participants
|
8 participants
n=10 Participants
|
|
Region of Enrollment
United States
|
8 participants
n=5 Participants
|
9 participants
n=7 Participants
|
13 participants
n=5 Participants
|
9 participants
n=4 Participants
|
9 participants
n=21 Participants
|
48 participants
n=10 Participants
|
PRIMARY outcome
Timeframe: ≤ 5 minutes predose, and 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 postdose on Day 1Population: The PK Analysis Sets included all enrolled participants who took at least 1 dose of study drug and had at least 1 nonmissing postdose concentration value reported by the PK laboratory for the corresponding analytes. A participant with normal hepatic function might serve as a matched control across cohorts evaluating the same cilofexor dose.
AUClast is defined as the concentration of drug from time zero to the last observable concentration.
Outcome measures
| Measure |
Cohort 2: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to moderate hepatic impairment participants, received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 3: Severe Hepatic Impairment
n=10 Participants
Participants with severe hepatic impairment received a single oral dose of cilofexor 10 mg (1 x 10 mg tablet) in a fed state, on Day 1.
|
Cohort 3: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to severe hepatic impairment participants, received a single oral dose of cilofexor 10 mg (1 x 10 mg tablet) in a fed state, on Day 1.
|
Cohort 1: Mild Hepatic Impairment
n=10 Participants
Participants with mild hepatic impairment received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 1: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to mild hepatic impairment participants, received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 2: Moderate Hepatic Impairment
n=10 Participants
Participants with moderate hepatic impairment received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
|---|---|---|---|---|---|---|
|
Pharmacokinetic (PK) Parameter: AUClast of Cilofexor
|
2756.7 h*ng/mL
Standard Deviation 851.38
|
6534.3 h*ng/mL
Standard Deviation 3791.05
|
960.0 h*ng/mL
Standard Deviation 352.71
|
5381.0 h*ng/mL
Standard Deviation 2175.34
|
2972.6 h*ng/mL
Standard Deviation 1230.49
|
8223.7 h*ng/mL
Standard Deviation 7492.41
|
PRIMARY outcome
Timeframe: ≤ 5 minutes predose, and 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 postdose on Day 1Population: Participants in the PK Analysis Set were analyzed. A participant with normal hepatic function might serve as a matched control across cohorts evaluating the same cilofexor dose.
AUCinf is defined as the concentration of drug extrapolated to infinite time.
Outcome measures
| Measure |
Cohort 2: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to moderate hepatic impairment participants, received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 3: Severe Hepatic Impairment
n=10 Participants
Participants with severe hepatic impairment received a single oral dose of cilofexor 10 mg (1 x 10 mg tablet) in a fed state, on Day 1.
|
Cohort 3: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to severe hepatic impairment participants, received a single oral dose of cilofexor 10 mg (1 x 10 mg tablet) in a fed state, on Day 1.
|
Cohort 1: Mild Hepatic Impairment
n=10 Participants
Participants with mild hepatic impairment received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 1: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to mild hepatic impairment participants, received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 2: Moderate Hepatic Impairment
n=10 Participants
Participants with moderate hepatic impairment received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
|---|---|---|---|---|---|---|
|
PK Parameter: AUCinf of Cilofexor
|
2805.6 h*ng/mL
Standard Deviation 851.26
|
6719.4 h*ng/mL
Standard Deviation 4056.73
|
986.2 h*ng/mL
Standard Deviation 354.93
|
5411.9 h*ng/mL
Standard Deviation 2181.82
|
3024.3 h*ng/mL
Standard Deviation 1224.02
|
8288.2 h*ng/mL
Standard Deviation 7583.42
|
PRIMARY outcome
Timeframe: ≤ 5 minutes predose, and 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 postdose on Day 1Population: Participants in the PK Analysis Set were analyzed. A participant with normal hepatic function might serve as a matched control across cohorts evaluating the same cilofexor dose.
Cmax is defined as the maximum concentration of drug.
Outcome measures
| Measure |
Cohort 2: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to moderate hepatic impairment participants, received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 3: Severe Hepatic Impairment
n=10 Participants
Participants with severe hepatic impairment received a single oral dose of cilofexor 10 mg (1 x 10 mg tablet) in a fed state, on Day 1.
|
Cohort 3: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to severe hepatic impairment participants, received a single oral dose of cilofexor 10 mg (1 x 10 mg tablet) in a fed state, on Day 1.
|
Cohort 1: Mild Hepatic Impairment
n=10 Participants
Participants with mild hepatic impairment received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 1: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to mild hepatic impairment participants, received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 2: Moderate Hepatic Impairment
n=10 Participants
Participants with moderate hepatic impairment received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
|---|---|---|---|---|---|---|
|
PK Parameter: Cmax of Cilofexor
|
495.7 ng/mL
Standard Deviation 199.45
|
426.6 ng/mL
Standard Deviation 136.40
|
182.4 ng/mL
Standard Deviation 86.67
|
994.1 ng/mL
Standard Deviation 533.38
|
603.5 ng/mL
Standard Deviation 275.33
|
909.2 ng/mL
Standard Deviation 477.20
|
PRIMARY outcome
Timeframe: ≤ 5 minutes predose, and 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 postdose on Day 1Population: Participants in the PK Analysis Set were analyzed. A participant with normal hepatic function might serve as a matched control across cohorts evaluating the same cilofexor dose.
%AUCexp is defined as the percentage of AUC extrapolated between AUClast and AUCinf.
Outcome measures
| Measure |
Cohort 2: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to moderate hepatic impairment participants, received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 3: Severe Hepatic Impairment
n=10 Participants
Participants with severe hepatic impairment received a single oral dose of cilofexor 10 mg (1 x 10 mg tablet) in a fed state, on Day 1.
|
Cohort 3: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to severe hepatic impairment participants, received a single oral dose of cilofexor 10 mg (1 x 10 mg tablet) in a fed state, on Day 1.
|
Cohort 1: Mild Hepatic Impairment
n=10 Participants
Participants with mild hepatic impairment received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 1: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to mild hepatic impairment participants, received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 2: Moderate Hepatic Impairment
n=10 Participants
Participants with moderate hepatic impairment received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
|---|---|---|---|---|---|---|
|
PK Parameter: %AUCexp of Cilofexor
|
1.87 percentage of AUCexp
Standard Deviation 1.653
|
1.81 percentage of AUCexp
Standard Deviation 1.874
|
2.96 percentage of AUCexp
Standard Deviation 1.962
|
0.63 percentage of AUCexp
Standard Deviation 0.270
|
1.95 percentage of AUCexp
Standard Deviation 1.621
|
0.64 percentage of AUCexp
Standard Deviation 0.194
|
PRIMARY outcome
Timeframe: ≤ 5 minutes predose, and 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 postdose on Day 1Population: Participants in the PK Analysis Set were analyzed. A participant with normal hepatic function might serve as a matched control across cohorts evaluating the same cilofexor dose.
Clast is defined as the last observable concentration of drug.
Outcome measures
| Measure |
Cohort 2: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to moderate hepatic impairment participants, received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 3: Severe Hepatic Impairment
n=10 Participants
Participants with severe hepatic impairment received a single oral dose of cilofexor 10 mg (1 x 10 mg tablet) in a fed state, on Day 1.
|
Cohort 3: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to severe hepatic impairment participants, received a single oral dose of cilofexor 10 mg (1 x 10 mg tablet) in a fed state, on Day 1.
|
Cohort 1: Mild Hepatic Impairment
n=10 Participants
Participants with mild hepatic impairment received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 1: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to mild hepatic impairment participants, received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 2: Moderate Hepatic Impairment
n=10 Participants
Participants with moderate hepatic impairment received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
|---|---|---|---|---|---|---|
|
PK Parameter: Clast of Cilofexor
|
3.73 ng/mL
Standard Deviation 2.378
|
6.03 ng/mL
Standard Deviation 8.044
|
2.18 ng/mL
Standard Deviation 1.387
|
1.97 ng/mL
Standard Deviation 1.005
|
3.84 ng/mL
Standard Deviation 2.162
|
2.76 ng/mL
Standard Deviation 3.377
|
PRIMARY outcome
Timeframe: ≤ 5 minutes predose, and 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 postdose on Day 1Population: Participants in the PK Analysis Set were analyzed. A participant with normal hepatic function might serve as a matched control across cohorts evaluating the same cilofexor dose.
Tmax is defined as the time (observed time point) of Cmax.
Outcome measures
| Measure |
Cohort 2: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to moderate hepatic impairment participants, received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 3: Severe Hepatic Impairment
n=10 Participants
Participants with severe hepatic impairment received a single oral dose of cilofexor 10 mg (1 x 10 mg tablet) in a fed state, on Day 1.
|
Cohort 3: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to severe hepatic impairment participants, received a single oral dose of cilofexor 10 mg (1 x 10 mg tablet) in a fed state, on Day 1.
|
Cohort 1: Mild Hepatic Impairment
n=10 Participants
Participants with mild hepatic impairment received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 1: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to mild hepatic impairment participants, received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 2: Moderate Hepatic Impairment
n=10 Participants
Participants with moderate hepatic impairment received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
|---|---|---|---|---|---|---|
|
PK Parameter: Tmax of Cilofexor
|
3.75 hours
Interval 2.5 to 4.0
|
5.00 hours
Interval 5.0 to 6.0
|
4.00 hours
Interval 3.0 to 5.0
|
3.75 hours
Interval 2.5 to 5.0
|
3.00 hours
Interval 2.5 to 4.0
|
4.50 hours
Interval 2.5 to 10.0
|
PRIMARY outcome
Timeframe: ≤ 5 minutes predose, and 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 postdose on Day 1Population: Participants in the PK Analysis Set were analyzed. A participant with normal hepatic function might serve as a matched control across cohorts evaluating the same cilofexor dose.
Tlast is defined as the time (observed time point) of Clast.
Outcome measures
| Measure |
Cohort 2: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to moderate hepatic impairment participants, received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 3: Severe Hepatic Impairment
n=10 Participants
Participants with severe hepatic impairment received a single oral dose of cilofexor 10 mg (1 x 10 mg tablet) in a fed state, on Day 1.
|
Cohort 3: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to severe hepatic impairment participants, received a single oral dose of cilofexor 10 mg (1 x 10 mg tablet) in a fed state, on Day 1.
|
Cohort 1: Mild Hepatic Impairment
n=10 Participants
Participants with mild hepatic impairment received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 1: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to mild hepatic impairment participants, received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 2: Moderate Hepatic Impairment
n=10 Participants
Participants with moderate hepatic impairment received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
|---|---|---|---|---|---|---|
|
PK Parameter: Tlast of Cilofexor
|
48.00 hours
Interval 24.0 to 72.0
|
96.00 hours
Interval 96.0 to 96.0
|
48.00 hours
Interval 24.0 to 48.0
|
64.80 hours
Interval 48.0 to 72.02
|
48.00 hours
Interval 24.0 to 72.0
|
72.00 hours
Interval 72.0 to 96.0
|
PRIMARY outcome
Timeframe: ≤ 5 minutes predose, and 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 postdose on Day 1Population: Participants in the PK Analysis Set were analyzed. A participant with normal hepatic function might serve as a matched control across cohorts evaluating the same cilofexor dose.
λz is defined as the terminal elimination rate constant, estimated by linear regression of the terminal elimination phase of the log plasma concentration of drug versus time curve of the drug.
Outcome measures
| Measure |
Cohort 2: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to moderate hepatic impairment participants, received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 3: Severe Hepatic Impairment
n=10 Participants
Participants with severe hepatic impairment received a single oral dose of cilofexor 10 mg (1 x 10 mg tablet) in a fed state, on Day 1.
|
Cohort 3: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to severe hepatic impairment participants, received a single oral dose of cilofexor 10 mg (1 x 10 mg tablet) in a fed state, on Day 1.
|
Cohort 1: Mild Hepatic Impairment
n=10 Participants
Participants with mild hepatic impairment received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 1: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to mild hepatic impairment participants, received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 2: Moderate Hepatic Impairment
n=10 Participants
Participants with moderate hepatic impairment received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
|---|---|---|---|---|---|---|
|
PK Parameter: λz of Cilofexor
|
0.100 1/hour
Standard Deviation 0.0655
|
0.045 1/hour
Standard Deviation 0.0117
|
0.099 1/hour
Standard Deviation 0.0659
|
0.070 1/hour
Standard Deviation 0.0377
|
0.099 1/hour
Standard Deviation 0.0661
|
0.051 1/hour
Standard Deviation 0.0152
|
PRIMARY outcome
Timeframe: ≤ 5 minutes predose, and 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 postdose on Day 1Population: Participants in the PK Analysis Set were analyzed. A participant with normal hepatic function might serve as a matched control across cohorts evaluating the same cilofexor dose.
CL/F is defined as the apparent oral clearance following administration of the drug.
Outcome measures
| Measure |
Cohort 2: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to moderate hepatic impairment participants, received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 3: Severe Hepatic Impairment
n=10 Participants
Participants with severe hepatic impairment received a single oral dose of cilofexor 10 mg (1 x 10 mg tablet) in a fed state, on Day 1.
|
Cohort 3: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to severe hepatic impairment participants, received a single oral dose of cilofexor 10 mg (1 x 10 mg tablet) in a fed state, on Day 1.
|
Cohort 1: Mild Hepatic Impairment
n=10 Participants
Participants with mild hepatic impairment received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 1: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to mild hepatic impairment participants, received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 2: Moderate Hepatic Impairment
n=10 Participants
Participants with moderate hepatic impairment received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
|---|---|---|---|---|---|---|
|
PK Parameter: CL/F of Cilofexor
|
11631.7 mL/h
Standard Deviation 3666.25
|
1963.1 mL/h
Standard Deviation 964.19
|
11535.9 mL/h
Standard Deviation 4627.39
|
6621.5 mL/h
Standard Deviation 3219.50
|
11324.4 mL/h
Standard Deviation 4184.32
|
5264.4 mL/h
Standard Deviation 2686.26
|
PRIMARY outcome
Timeframe: ≤ 5 minutes predose, and 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 postdose on Day 1Population: Participants in the PK Analysis Set were analyzed. A participant with normal hepatic function might serve as a matched control across cohorts evaluating the same cilofexor dose.
Vz/F is defined as the apparent volume of distribution of the drug.
Outcome measures
| Measure |
Cohort 2: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to moderate hepatic impairment participants, received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 3: Severe Hepatic Impairment
n=10 Participants
Participants with severe hepatic impairment received a single oral dose of cilofexor 10 mg (1 x 10 mg tablet) in a fed state, on Day 1.
|
Cohort 3: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to severe hepatic impairment participants, received a single oral dose of cilofexor 10 mg (1 x 10 mg tablet) in a fed state, on Day 1.
|
Cohort 1: Mild Hepatic Impairment
n=10 Participants
Participants with mild hepatic impairment received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 1: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to mild hepatic impairment participants, received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 2: Moderate Hepatic Impairment
n=10 Participants
Participants with moderate hepatic impairment received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
|---|---|---|---|---|---|---|
|
PK Parameter: Vz/F of Cilofexor
|
153854.9 mL
Standard Deviation 83844.37
|
41375.1 mL
Standard Deviation 11767.71
|
160423.9 mL
Standard Deviation 92259.03
|
97797.6 mL
Standard Deviation 18500.74
|
148898.5 mL
Standard Deviation 81520.19
|
99541.7 mL
Standard Deviation 31192.41
|
PRIMARY outcome
Timeframe: ≤ 5 minutes predose, and 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 postdose on Day 1Population: Participants in the PK Analysis Set were analyzed. A participant with normal hepatic function might serve as a matched control across cohorts evaluating the same cilofexor dose.
t1/2 is defined as the estimate of the terminal elimination half-life of the drug.
Outcome measures
| Measure |
Cohort 2: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to moderate hepatic impairment participants, received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 3: Severe Hepatic Impairment
n=10 Participants
Participants with severe hepatic impairment received a single oral dose of cilofexor 10 mg (1 x 10 mg tablet) in a fed state, on Day 1.
|
Cohort 3: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to severe hepatic impairment participants, received a single oral dose of cilofexor 10 mg (1 x 10 mg tablet) in a fed state, on Day 1.
|
Cohort 1: Mild Hepatic Impairment
n=10 Participants
Participants with mild hepatic impairment received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 1: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to mild hepatic impairment participants, received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 2: Moderate Hepatic Impairment
n=10 Participants
Participants with moderate hepatic impairment received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
|---|---|---|---|---|---|---|
|
PK Parameter: t1/2 of Cilofexor
|
8.12 hours
Interval 4.9 to 15.02
|
15.90 hours
Interval 12.85 to 19.02
|
9.31 hours
Interval 5.15 to 11.61
|
11.45 hours
Interval 8.5 to 12.94
|
9.49 hours
Interval 4.78 to 11.67
|
13.53 hours
Interval 11.56 to 18.15
|
SECONDARY outcome
Timeframe: Day 1 up to Day 31Population: The Safety Analysis Set included all participants who took at least 1 dose of study drug.
Outcome measures
| Measure |
Cohort 2: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to moderate hepatic impairment participants, received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 3: Severe Hepatic Impairment
n=10 Participants
Participants with severe hepatic impairment received a single oral dose of cilofexor 10 mg (1 x 10 mg tablet) in a fed state, on Day 1.
|
Cohort 3: Normal Hepatic Function
Matched normal hepatic function participants to severe hepatic impairment participants, received a single oral dose of cilofexor 10 mg (1 x 10 mg tablet) in a fed state, on Day 1.
|
Cohort 1: Mild Hepatic Impairment
n=10 Participants
Participants with mild hepatic impairment received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 1: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to mild hepatic impairment participants, received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 2: Moderate Hepatic Impairment
n=16 Participants
Participants with moderate hepatic impairment received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
|---|---|---|---|---|---|---|
|
Percentage of Participants Experiencing Treatment-Emergent Adverse Events
|
30.0 percentage of participants
|
0 percentage of participants
|
—
|
10.0 percentage of participants
|
20.0 percentage of participants
|
12.5 percentage of participants
|
SECONDARY outcome
Timeframe: Day 1 up to Day 31Population: Participants in the Safety Analysis Set were analyzed.
A treatment-emergent laboratory abnormality was defined as an increase of at least 1 toxicity grade from predose at any time postdose up to and including the date of last study drug dose plus 30 days. The most severe graded abnormality from all tests was counted for each participant.
Outcome measures
| Measure |
Cohort 2: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to moderate hepatic impairment participants, received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 3: Severe Hepatic Impairment
n=10 Participants
Participants with severe hepatic impairment received a single oral dose of cilofexor 10 mg (1 x 10 mg tablet) in a fed state, on Day 1.
|
Cohort 3: Normal Hepatic Function
Matched normal hepatic function participants to severe hepatic impairment participants, received a single oral dose of cilofexor 10 mg (1 x 10 mg tablet) in a fed state, on Day 1.
|
Cohort 1: Mild Hepatic Impairment
n=10 Participants
Participants with mild hepatic impairment received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 1: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to mild hepatic impairment participants, received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 2: Moderate Hepatic Impairment
n=16 Participants
Participants with moderate hepatic impairment received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
|---|---|---|---|---|---|---|
|
Percentage of Participants Who Experienced Graded Laboratory Abnormalities
Any Laboratory Abnormality
|
100.0 percentage of participants
|
60.0 percentage of participants
|
—
|
90.0 percentage of participants
|
100.0 percentage of participants
|
50.0 percentage of participants
|
|
Percentage of Participants Who Experienced Graded Laboratory Abnormalities
Grade 3 or above Laboratory Abnormalities
|
40.0 percentage of participants
|
0 percentage of participants
|
—
|
20.0 percentage of participants
|
20.0 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: 0.5 hour predose, ≤ 5 minutes predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, and 16 hours postdose on Day -1 and Day 1; 4.5 hours postdose on Day -1; 24, 48, 72, and 96 hours postdose on Day 1Population: Participants in the PD Analysis Set were analyzed. A participant with normal hepatic function might serve as a matched control across cohorts evaluating the same cilofexor dose.
AUC2-12 is defined as area under the curve calculated by the trapezoidal rule for the time from 2 to 12 hours. For PD assessments on Day -1, participants were administered a single oral dose of placebo-to-match cilofexor tablet on Day -1; the reported Time Frame is with respect to the placebo dosing.
Outcome measures
| Measure |
Cohort 2: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to moderate hepatic impairment participants, received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 3: Severe Hepatic Impairment
n=10 Participants
Participants with severe hepatic impairment received a single oral dose of cilofexor 10 mg (1 x 10 mg tablet) in a fed state, on Day 1.
|
Cohort 3: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to severe hepatic impairment participants, received a single oral dose of cilofexor 10 mg (1 x 10 mg tablet) in a fed state, on Day 1.
|
Cohort 1: Mild Hepatic Impairment
n=10 Participants
Participants with mild hepatic impairment received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 1: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to mild hepatic impairment participants, received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 2: Moderate Hepatic Impairment
n=10 Participants
Participants with moderate hepatic impairment received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
|---|---|---|---|---|---|---|
|
Pharmacodynamic (PD) Parameter: Mean Day 1/ Day -1 Ratio of AUC2-12 for α-hydroxy-4-cholesten-3-one (C4)
|
0.681 ratio
Standard Deviation 0.2614
|
1.063 ratio
Standard Deviation 0.2469
|
0.978 ratio
Standard Deviation 0.4155
|
0.706 ratio
Standard Deviation 0.2273
|
0.817 ratio
Standard Deviation 0.2836
|
0.716 ratio
Standard Deviation 0.2370
|
SECONDARY outcome
Timeframe: 0.5 hour predose, ≤ 5 minutes predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, and 16 hours postdose on Day -1 and Day 1; 4.5 hours postdose on Day -1; 24, 48, 72, and 96 hours postdose on Day 1Population: Participants in the PD Analysis Set were analyzed. A participant with normal hepatic function might serve as a matched control across cohorts evaluating the same cilofexor dose.
Cmin for C4 is defined as the minimum observed concentration of C4. For PD assessments on Day -1, participants were administered a single oral dose of placebo-to-match cilofexor tablet on Day -1; the reported Time Frame is with respect to the placebo dosing.
Outcome measures
| Measure |
Cohort 2: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to moderate hepatic impairment participants, received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 3: Severe Hepatic Impairment
n=10 Participants
Participants with severe hepatic impairment received a single oral dose of cilofexor 10 mg (1 x 10 mg tablet) in a fed state, on Day 1.
|
Cohort 3: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to severe hepatic impairment participants, received a single oral dose of cilofexor 10 mg (1 x 10 mg tablet) in a fed state, on Day 1.
|
Cohort 1: Mild Hepatic Impairment
n=10 Participants
Participants with mild hepatic impairment received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 1: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to mild hepatic impairment participants, received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 2: Moderate Hepatic Impairment
n=10 Participants
Participants with moderate hepatic impairment received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
|---|---|---|---|---|---|---|
|
PD Parameter: Mean Day 1/ Day -1 Ratio of Cmin for α-hydroxy-4-cholesten-3-one (C4)
|
0.583 ratio
Standard Deviation 0.1634
|
0.953 ratio
Standard Deviation 0.2073
|
0.727 ratio
Standard Deviation 0.2674
|
0.599 ratio
Standard Deviation 0.3272
|
0.707 ratio
Standard Deviation 0.2838
|
0.668 ratio
Standard Deviation 0.2384
|
SECONDARY outcome
Timeframe: 0.5 hour predose, ≤ 5 minutes predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, and 16 hours postdose on Day -1 and Day 1; 4.5 hours postdose on Day -1; 24, 48, 72, and 96 hours postdose on Day 1Population: Participants in the PD Analysis Set were analyzed. A participant with normal hepatic function might serve as a matched control across cohorts evaluating the same cilofexor dose.
AUC2-12 is defined as area under the curve calculated by the trapezoidal rule for the time from 2 to 12 hours. For PD assessments on Day -1, participants were administered a single oral dose of placebo-to-match cilofexor tablet on Day -1; the reported Time Frame is with respect to the placebo dosing.
Outcome measures
| Measure |
Cohort 2: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to moderate hepatic impairment participants, received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 3: Severe Hepatic Impairment
n=10 Participants
Participants with severe hepatic impairment received a single oral dose of cilofexor 10 mg (1 x 10 mg tablet) in a fed state, on Day 1.
|
Cohort 3: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to severe hepatic impairment participants, received a single oral dose of cilofexor 10 mg (1 x 10 mg tablet) in a fed state, on Day 1.
|
Cohort 1: Mild Hepatic Impairment
n=10 Participants
Participants with mild hepatic impairment received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 1: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to mild hepatic impairment participants, received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 2: Moderate Hepatic Impairment
n=10 Participants
Participants with moderate hepatic impairment received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
|---|---|---|---|---|---|---|
|
PD Parameter: Mean Day 1/ Day -1 Ratio of AUC2-12 for Fibroblast Growth Factor 19 (FGF19)
|
2.848 ratio
Standard Deviation 1.0250
|
1.582 ratio
Standard Deviation 0.8182
|
2.179 ratio
Standard Deviation 1.6972
|
3.031 ratio
Standard Deviation 1.0376
|
2.840 ratio
Standard Deviation 0.9254
|
3.730 ratio
Standard Deviation 1.3768
|
SECONDARY outcome
Timeframe: 0.5 hour predose, ≤ 5 minutes predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, and 16 hours postdose on Day -1 and Day 1; 4.5 hours postdose on Day -1; 24, 48, 72, and 96 hours postdose on Day 1Population: Participants in the PD Analysis Set were analyzed. A participant with normal hepatic function might serve as a matched control across cohorts evaluating the same cilofexor dose.
Cmax for FGF19 is defined as the maximum observed concentration of FGF19. For PD assessments on Day -1, participants were administered a single oral dose of placebo-to-match cilofexor tablet on Day -1; the reported Time Frame is with respect to the placebo dosing.
Outcome measures
| Measure |
Cohort 2: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to moderate hepatic impairment participants, received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 3: Severe Hepatic Impairment
n=10 Participants
Participants with severe hepatic impairment received a single oral dose of cilofexor 10 mg (1 x 10 mg tablet) in a fed state, on Day 1.
|
Cohort 3: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to severe hepatic impairment participants, received a single oral dose of cilofexor 10 mg (1 x 10 mg tablet) in a fed state, on Day 1.
|
Cohort 1: Mild Hepatic Impairment
n=10 Participants
Participants with mild hepatic impairment received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 1: Normal Hepatic Function
n=10 Participants
Matched normal hepatic function participants to mild hepatic impairment participants, received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 2: Moderate Hepatic Impairment
n=10 Participants
Participants with moderate hepatic impairment received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
|---|---|---|---|---|---|---|
|
PD Parameter: Mean Day 1/ Day -1 Ratio of Cmax for Fibroblast Growth Factor 19 (FGF19)
|
3.145 ratio
Standard Deviation 1.4484
|
1.899 ratio
Standard Deviation 1.1619
|
2.098 ratio
Standard Deviation 1.1579
|
3.778 ratio
Standard Deviation 1.4954
|
3.494 ratio
Standard Deviation 1.4423
|
4.459 ratio
Standard Deviation 1.9899
|
Adverse Events
Cohort 1: Mild Hepatic Impairment
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Cohort 2: Moderate Hepatic Impairment
Serious events: 1 serious events
Other events: 1 other events
Deaths: 0 deaths
Cohort 1 and 2: Normal Hepatic Function
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Cohort 3: Severe Hepatic Impairment
Serious events: 1 serious events
Other events: 2 other events
Deaths: 0 deaths
Cohort 3: Normal Hepatic Function
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Cohort 1: Mild Hepatic Impairment
n=10 participants at risk
Participants with mild hepatic impairment received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 2: Moderate Hepatic Impairment
n=10 participants at risk
Participants with moderate hepatic impairment received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 1 and 2: Normal Hepatic Function
n=16 participants at risk
Matched normal hepatic function participants to mild or moderate hepatic impairment participants, received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 3: Severe Hepatic Impairment
n=10 participants at risk
Participants with severe hepatic impairment received a single oral dose of cilofexor 10 mg (1 x 10 mg tablet) in a fed state, on Day 1.
|
Cohort 3: Normal Hepatic Function
n=10 participants at risk
Matched normal hepatic function participants to severe hepatic impairment participants, received a single oral dose of cilofexor 10 mg (1 x 10 mg tablet) in a fed state, on Day 1.
|
|---|---|---|---|---|---|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.00%
0/10 • Day 1 up to Day 31
The Safety Analysis Set included all participants who took at least 1 dose of study drug.
|
10.0%
1/10 • Day 1 up to Day 31
The Safety Analysis Set included all participants who took at least 1 dose of study drug.
|
0.00%
0/16 • Day 1 up to Day 31
The Safety Analysis Set included all participants who took at least 1 dose of study drug.
|
0.00%
0/10 • Day 1 up to Day 31
The Safety Analysis Set included all participants who took at least 1 dose of study drug.
|
0.00%
0/10 • Day 1 up to Day 31
The Safety Analysis Set included all participants who took at least 1 dose of study drug.
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.00%
0/10 • Day 1 up to Day 31
The Safety Analysis Set included all participants who took at least 1 dose of study drug.
|
0.00%
0/10 • Day 1 up to Day 31
The Safety Analysis Set included all participants who took at least 1 dose of study drug.
|
0.00%
0/16 • Day 1 up to Day 31
The Safety Analysis Set included all participants who took at least 1 dose of study drug.
|
10.0%
1/10 • Day 1 up to Day 31
The Safety Analysis Set included all participants who took at least 1 dose of study drug.
|
0.00%
0/10 • Day 1 up to Day 31
The Safety Analysis Set included all participants who took at least 1 dose of study drug.
|
Other adverse events
| Measure |
Cohort 1: Mild Hepatic Impairment
n=10 participants at risk
Participants with mild hepatic impairment received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 2: Moderate Hepatic Impairment
n=10 participants at risk
Participants with moderate hepatic impairment received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 1 and 2: Normal Hepatic Function
n=16 participants at risk
Matched normal hepatic function participants to mild or moderate hepatic impairment participants, received a single oral dose of cilofexor 30 mg (3 x 10 mg tablets) in a fed state, on Day 1.
|
Cohort 3: Severe Hepatic Impairment
n=10 participants at risk
Participants with severe hepatic impairment received a single oral dose of cilofexor 10 mg (1 x 10 mg tablet) in a fed state, on Day 1.
|
Cohort 3: Normal Hepatic Function
n=10 participants at risk
Matched normal hepatic function participants to severe hepatic impairment participants, received a single oral dose of cilofexor 10 mg (1 x 10 mg tablet) in a fed state, on Day 1.
|
|---|---|---|---|---|---|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/10 • Day 1 up to Day 31
The Safety Analysis Set included all participants who took at least 1 dose of study drug.
|
10.0%
1/10 • Day 1 up to Day 31
The Safety Analysis Set included all participants who took at least 1 dose of study drug.
|
0.00%
0/16 • Day 1 up to Day 31
The Safety Analysis Set included all participants who took at least 1 dose of study drug.
|
0.00%
0/10 • Day 1 up to Day 31
The Safety Analysis Set included all participants who took at least 1 dose of study drug.
|
0.00%
0/10 • Day 1 up to Day 31
The Safety Analysis Set included all participants who took at least 1 dose of study drug.
|
|
Injury, poisoning and procedural complications
Skin abrasion
|
0.00%
0/10 • Day 1 up to Day 31
The Safety Analysis Set included all participants who took at least 1 dose of study drug.
|
0.00%
0/10 • Day 1 up to Day 31
The Safety Analysis Set included all participants who took at least 1 dose of study drug.
|
0.00%
0/16 • Day 1 up to Day 31
The Safety Analysis Set included all participants who took at least 1 dose of study drug.
|
10.0%
1/10 • Day 1 up to Day 31
The Safety Analysis Set included all participants who took at least 1 dose of study drug.
|
0.00%
0/10 • Day 1 up to Day 31
The Safety Analysis Set included all participants who took at least 1 dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/10 • Day 1 up to Day 31
The Safety Analysis Set included all participants who took at least 1 dose of study drug.
|
0.00%
0/10 • Day 1 up to Day 31
The Safety Analysis Set included all participants who took at least 1 dose of study drug.
|
0.00%
0/16 • Day 1 up to Day 31
The Safety Analysis Set included all participants who took at least 1 dose of study drug.
|
10.0%
1/10 • Day 1 up to Day 31
The Safety Analysis Set included all participants who took at least 1 dose of study drug.
|
0.00%
0/10 • Day 1 up to Day 31
The Safety Analysis Set included all participants who took at least 1 dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/10 • Day 1 up to Day 31
The Safety Analysis Set included all participants who took at least 1 dose of study drug.
|
0.00%
0/10 • Day 1 up to Day 31
The Safety Analysis Set included all participants who took at least 1 dose of study drug.
|
6.2%
1/16 • Day 1 up to Day 31
The Safety Analysis Set included all participants who took at least 1 dose of study drug.
|
0.00%
0/10 • Day 1 up to Day 31
The Safety Analysis Set included all participants who took at least 1 dose of study drug.
|
0.00%
0/10 • Day 1 up to Day 31
The Safety Analysis Set included all participants who took at least 1 dose of study drug.
|
|
Nervous system disorders
Headache
|
0.00%
0/10 • Day 1 up to Day 31
The Safety Analysis Set included all participants who took at least 1 dose of study drug.
|
0.00%
0/10 • Day 1 up to Day 31
The Safety Analysis Set included all participants who took at least 1 dose of study drug.
|
6.2%
1/16 • Day 1 up to Day 31
The Safety Analysis Set included all participants who took at least 1 dose of study drug.
|
0.00%
0/10 • Day 1 up to Day 31
The Safety Analysis Set included all participants who took at least 1 dose of study drug.
|
0.00%
0/10 • Day 1 up to Day 31
The Safety Analysis Set included all participants who took at least 1 dose of study drug.
|
|
Vascular disorders
Haematoma
|
10.0%
1/10 • Day 1 up to Day 31
The Safety Analysis Set included all participants who took at least 1 dose of study drug.
|
0.00%
0/10 • Day 1 up to Day 31
The Safety Analysis Set included all participants who took at least 1 dose of study drug.
|
0.00%
0/16 • Day 1 up to Day 31
The Safety Analysis Set included all participants who took at least 1 dose of study drug.
|
0.00%
0/10 • Day 1 up to Day 31
The Safety Analysis Set included all participants who took at least 1 dose of study drug.
|
0.00%
0/10 • Day 1 up to Day 31
The Safety Analysis Set included all participants who took at least 1 dose of study drug.
|
Additional Information
Gilead Clinical Study Information Center
Gilead Sciences
Phone: 1-833-445-3230 (GILEAD-0)
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee 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
- Publication restrictions are in place
Restriction type: OTHER