Pharmacokinetics and Pharmacodynamics of Cilofexor in Adults With Normal and Impaired Hepatic Function
Sponsor
Gilead Sciences (Industry)
Overall Status
Completed
CT.gov ID
NCT02808312
Collaborator
(none)
57
5
6
27.1
11.4
0.4
Study Details
Study Description
Brief Summary
The primary objective of this study is to evaluate the single-dose pharmacokinetics of cilofexor in adults with impaired hepatic function relative to matched, healthy controls with normal hepatic function.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
57 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1 Open-Label, Parallel-Group, Adaptive, Single-Dose Study to Evaluate the Pharmacokinetics and Pharmacodynamics of GS-9674 in Subjects With Normal and Impaired Hepatic Function
Actual Study Start Date
:
Jul 13, 2016
Actual Primary Completion Date
:
Oct 16, 2018
Actual Study Completion Date
:
Oct 16, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort 1: Mild Hepatic Impairment Participants with mild hepatic impairment will receive a single oral dose of cilofexor 30 mg (3 x 10 mg tablets). |
Drug: Cilofexor
Tablet(s) administered orally in a fed state on Day 1
Other Names:
|
| Experimental: Cohort 1: Normal Hepatic Function Matched normal hepatic function participants to mild hepatic impairment participants will receive a single oral dose of cilofexor 30 mg (3 x 10 mg tablets). |
Drug: Cilofexor
Tablet(s) administered orally in a fed state on Day 1
Other Names:
|
| Experimental: Cohort 2: Moderate Hepatic Impairment Participants with moderate hepatic impairment will receive a single oral dose of cilofexor 30 mg (3 x 10 mg tablets). |
Drug: Cilofexor
Tablet(s) administered orally in a fed state on Day 1
Other Names:
|
| Experimental: Cohort 2: Normal Hepatic Function Matched normal hepatic function participants to moderate hepatic impairment participants will receive a single oral dose of cilofexor 30 mg (3 x 10 mg tablets). |
Drug: Cilofexor
Tablet(s) administered orally in a fed state on Day 1
Other Names:
|
| Experimental: Cohort 3: Severe Hepatic Impairment Participants with severe hepatic impairment will receive a single oral dose of cilofexor 10 mg (1 x 10 mg tablet). |
Drug: Cilofexor
Tablet(s) administered orally in a fed state on Day 1
Other Names:
|
| Experimental: Cohort 3: Normal Hepatic Function Matched normal hepatic function participants to severe hepatic impairment participants will receive a single oral dose of cilofexor 10 mg (1 x 10 mg tablet). |
Drug: Cilofexor
Tablet(s) administered orally in a fed state on Day 1
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Pharmacokinetic (PK) Parameter: AUClast of Cilofexor [≤ 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]
AUClast is defined as the concentration of drug from time zero to the last observable concentration.
- PK Parameter: AUCinf of Cilofexor [≤ 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]
AUCinf is defined as the concentration of drug extrapolated to infinite time.
- PK Parameter: Cmax of Cilofexor [≤ 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]
Cmax is defined as the maximum concentration of drug.
- PK Parameter: %AUCexp of Cilofexor [≤ 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]
%AUCexp is defined as the percentage of AUC extrapolated between AUClast and AUCinf.
- PK Parameter: Clast of Cilofexor [≤ 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]
Clast is defined as the last observable concentration of drug.
- PK Parameter: Tmax of Cilofexor [≤ 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]
Tmax is defined as the time (observed time point) of Cmax.
- PK Parameter: Tlast of Cilofexor [≤ 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]
Tlast is defined as the time (observed time point) of Clast.
- PK Parameter: λz of Cilofexor [≤ 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]
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.
- PK Parameter: CL/F of Cilofexor [≤ 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]
CL/F is defined as the apparent oral clearance following administration of the drug.
- PK Parameter: Vz/F of Cilofexor [≤ 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]
Vz/F is defined as the apparent volume of distribution of the drug.
- PK Parameter: t1/2 of Cilofexor [≤ 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]
t1/2 is defined as the estimate of the terminal elimination half-life of the drug.
Secondary Outcome Measures
- Percentage of Participants Experiencing Treatment-Emergent Adverse Events [Day 1 up to Day 31]
- Percentage of Participants Who Experienced Graded Laboratory Abnormalities [Day 1 up to Day 31]
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.
- Pharmacodynamic (PD) Parameter: Mean Day 1/ Day -1 Ratio of AUC2-12 for α-hydroxy-4-cholesten-3-one (C4) [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 1]
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.
- PD Parameter: Mean Day 1/ Day -1 Ratio of Cmin for α-hydroxy-4-cholesten-3-one (C4) [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 1]
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.
- PD Parameter: Mean Day 1/ Day -1 Ratio of AUC2-12 for Fibroblast Growth Factor 19 (FGF19) [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 1]
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.
- PD Parameter: Mean Day 1/ Day -1 Ratio of Cmax for Fibroblast Growth Factor 19 (FGF19) [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 1]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Key Inclusion Criteria:
Cohort 1:
-
Individuals with mildly impaired and normal hepatic function.
-
Individuals with mild hepatic impairment must have a score of 5-6 on the Child-Pugh-Turcotte (CPT) classification at screening without evidence of worsening clinical and/or laboratory signs of hepatic impairment within 2 months prior or within the screening period.
Cohort 2:
-
Individuals with moderately impaired and normal hepatic function.
-
Individuals with moderate hepatic impairment must have a score of 7-9 on the CPT classification at screening without evidence of worsening clinical and/or laboratory signs of hepatic impairment within 2 months prior or within the screening period.
Cohort 3:
-
Individuals with severely impaired and normal hepatic function.
-
Individuals with severe hepatic impairment must have a score of 10-15 on the CPT classification at screening without evidence of worsening clinical and/or laboratory signs of hepatic impairment within 2 months prior or within the screening period.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Miami | Florida | United States | 33014 | |
| 2 | Orlando | Florida | United States | 32809 | |
| 3 | Knoxville | Tennessee | United States | 37920 | |
| 4 | San Antonio | Texas | United States | 78215 | |
| 5 | Auckland | New Zealand | 1640 |
Sponsors and Collaborators
- Gilead Sciences
Investigators
- Study Director: Gilead Study Director, Gilead Sciences
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT02808312
Other Study ID Numbers:
- GS-US-402-3885
First Posted:
Jun 21, 2016
Last Update Posted:
Jan 7, 2021
Last Verified:
Dec 1, 2020
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants were enrolled at 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. |
|---|---|
| Pre-assignment Detail | 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. |
| Arm/Group Title | Cohort 1: Mild Hepatic Impairment | Cohort 2: Moderate Hepatic Impairment | Cohort 1 & 2: Normal Hepatic Function | Cohort 3: Severe Hepatic Impairment | Cohort 3: Normal Hepatic Function |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. |
| Period Title: Overall Study | |||||
| STARTED | 10 | 10 | 17 | 10 | 10 |
| COMPLETED | 10 | 10 | 16 | 10 | 10 |
| NOT COMPLETED | 0 | 0 | 1 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Cohort 1: Mild Hepatic Impairment | Cohort 2: Moderate Hepatic Impairment | Cohort 1 & 2: Normal Hepatic Function | Cohort 3: Severe Hepatic Impairment | Cohort 3: Normal Hepatic Function | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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 of all reporting groups |
| Overall Participants | 10 | 10 | 16 | 10 | 10 | 56 |
| Age (years) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [years] |
54
(10.1)
|
57
(8.9)
|
55
(7.6)
|
54
(9.5)
|
52
(8.4)
|
54.45
(8.67)
|
| Sex: Female, Male (Count of Participants) | ||||||
| Female |
3
30%
|
2
20%
|
5
31.3%
|
3
30%
|
3
30%
|
16
28.6%
|
| Male |
7
70%
|
8
80%
|
11
68.8%
|
7
70%
|
7
70%
|
40
71.4%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||||
| Hispanic or Latino |
4
40%
|
3
30%
|
7
43.8%
|
6
60%
|
5
50%
|
25
44.6%
|
| Not Hispanic or Latino |
6
60%
|
7
70%
|
9
56.3%
|
4
40%
|
5
50%
|
31
55.4%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | ||||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
1
10%
|
0
0%
|
1
6.3%
|
0
0%
|
0
0%
|
2
3.6%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
1
10%
|
0
0%
|
0
0%
|
1
10%
|
1
10%
|
3
5.4%
|
| White |
8
80%
|
10
100%
|
15
93.8%
|
9
90%
|
9
90%
|
51
91.1%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | ||||||
| New Zealand |
2
20%
|
1
10%
|
3
18.8%
|
1
10%
|
1
10%
|
8
14.3%
|
| United States |
8
80%
|
9
90%
|
13
81.3%
|
9
90%
|
9
90%
|
48
85.7%
|
Outcome Measures
| Title | Pharmacokinetic (PK) Parameter: AUClast of Cilofexor |
|---|---|
| Description | AUClast is defined as the concentration of drug from time zero to the last observable concentration. |
| Time Frame | ≤ 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Cohort 1: Mild Hepatic Impairment | Cohort 1: Normal Hepatic Function | Cohort 2: Moderate Hepatic Impairment | Cohort 2: Normal Hepatic Function | Cohort 3: Severe Hepatic Impairment | Cohort 3: Normal Hepatic Function |
|---|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. | 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. |
| Measure Participants | 10 | 10 | 10 | 10 | 10 | 10 |
| Mean (Standard Deviation) [h*ng/mL] |
5381.0
(2175.34)
|
2972.6
(1230.49)
|
8223.7
(7492.41)
|
2756.7
(851.38)
|
6534.3
(3791.05)
|
960.0
(352.71)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Mild Hepatic Impairment, Cohort 1: Normal Hepatic Function |
|---|---|---|
| Comments | An analysis of variance (ANOVA) model with hepatic function group as a fixed effect was fitted to the natural logarithmic transformation of PK parameters (AUClast) for each cohort. | |
| Type of Statistical Test | Other | |
| Comments | Two-sided 90% Confidence Intervals (CIs) were calculated for the ratios of geometric least-squares means (GLSMs) of PK parameters between mild hepatic impairment group and the control (normal hepatic function) group. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GLSM ratio |
| Estimated Value | 1.7869 | |
| Confidence Interval |
(2-Sided) 90% 1.2885 to 2.4781 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: Moderate Hepatic Impairment, Cohort 2: Normal Hepatic Function |
|---|---|---|
| Comments | An ANOVA model with hepatic function group as a fixed effect was fitted to the natural logarithmic transformation of PK parameters (AUClast) for each cohort. | |
| Type of Statistical Test | Other | |
| Comments | Two-sided 90% CIs were calculated for the ratios of GLSMs of PK parameters between moderate hepatic impairment group and the control (normal hepatic function) group. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GLSM ratio |
| Estimated Value | 2.4868 | |
| Confidence Interval |
(2-Sided) 90% 1.6735 to 3.6954 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Cohort 3: Severe Hepatic Impairment, Cohort 3: Normal Hepatic Function |
|---|---|---|
| Comments | An ANOVA model with hepatic function group as a fixed effect was fitted to the natural logarithmic transformation of PK parameters (AUClast) for each cohort. | |
| Type of Statistical Test | Other | |
| Comments | Two-sided 90% CIs were calculated for the ratios of GLSMs of PK parameters between severe hepatic impairment group and the control (normal hepatic function) group. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GLSM ratio |
| Estimated Value | 6.3240 | |
| Confidence Interval |
(2-Sided) 90% 4.3675 to 9.1569 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | PK Parameter: AUCinf of Cilofexor |
|---|---|
| Description | AUCinf is defined as the concentration of drug extrapolated to infinite time. |
| Time Frame | ≤ 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Cohort 1: Mild Hepatic Impairment | Cohort 1: Normal Hepatic Function | Cohort 2: Moderate Hepatic Impairment | Cohort 2: Normal Hepatic Function | Cohort 3: Severe Hepatic Impairment | Cohort 3: Normal Hepatic Function |
|---|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. | 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. |
| Measure Participants | 10 | 10 | 10 | 10 | 10 | 10 |
| Mean (Standard Deviation) [h*ng/mL] |
5411.9
(2181.82)
|
3024.3
(1224.02)
|
8288.2
(7583.42)
|
2805.6
(851.26)
|
6719.4
(4056.73)
|
986.2
(354.93)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Mild Hepatic Impairment, Cohort 1: Normal Hepatic Function |
|---|---|---|
| Comments | An ANOVA model with hepatic function group as a fixed effect was fitted to the natural logarithmic transformation of PK parameters (AUCinf) for each cohort. | |
| Type of Statistical Test | Other | |
| Comments | Two-sided 90% CIs were calculated for the ratios of GLSMs of PK parameters between mild hepatic impairment group and the control (normal hepatic function) group. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GLSM ratio |
| Estimated Value | 1.7628 | |
| Confidence Interval |
(2-Sided) 90% 1.2750 to 2.4374 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: Moderate Hepatic Impairment, Cohort 2: Normal Hepatic Function |
|---|---|---|
| Comments | An ANOVA model with hepatic function group as a fixed effect was fitted to the natural logarithmic transformation of PK parameters (AUCinf) for each cohort. | |
| Type of Statistical Test | Other | |
| Comments | Two-sided 90% CIs were calculated for the ratios of GLSMs of PK parameters between moderate hepatic impairment group and the control (normal hepatic function) group. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GLSM ratio |
| Estimated Value | 2.4559 | |
| Confidence Interval |
(2-Sided) 90% 1.6531 to 3.6486 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Cohort 3: Severe Hepatic Impairment, Cohort 3: Normal Hepatic Function |
|---|---|---|
| Comments | An ANOVA model with hepatic function group as a fixed effect was fitted to the natural logarithmic transformation of PK parameters (AUCinf) for each cohort. | |
| Type of Statistical Test | Other | |
| Comments | Two-sided 90% CIs were calculated for the ratios of GLSMs of PK parameters between severe hepatic impairment group and the control (normal hepatic function) group. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GLSM ratio |
| Estimated Value | 6.2497 | |
| Confidence Interval |
(2-Sided) 90% 4.2965 to 9.0910 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | PK Parameter: Cmax of Cilofexor |
|---|---|
| Description | Cmax is defined as the maximum concentration of drug. |
| Time Frame | ≤ 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Cohort 1: Mild Hepatic Impairment | Cohort 1: Normal Hepatic Function | Cohort 2: Moderate Hepatic Impairment | Cohort 2: Normal Hepatic Function | Cohort 3: Severe Hepatic Impairment | Cohort 3: Normal Hepatic Function |
|---|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. | 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. |
| Measure Participants | 10 | 10 | 10 | 10 | 10 | 10 |
| Mean (Standard Deviation) [ng/mL] |
994.1
(533.38)
|
603.5
(275.33)
|
909.2
(477.20)
|
495.7
(199.45)
|
426.6
(136.40)
|
182.4
(86.67)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Mild Hepatic Impairment, Cohort 1: Normal Hepatic Function |
|---|---|---|
| Comments | An ANOVA model with hepatic function group as a fixed effect was fitted to the natural logarithmic transformation of PK parameters (Cmax) for each cohort. | |
| Type of Statistical Test | Other | |
| Comments | Two-sided 90% CIs were calculated for the ratios of GLSMs of PK parameters between mild hepatic impairment group and the control (normal hepatic function) group. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GLSM ratio |
| Estimated Value | 1.5703 | |
| Confidence Interval |
(2-Sided) 90% 1.0723 to 2.2995 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: Moderate Hepatic Impairment, Cohort 2: Normal Hepatic Function |
|---|---|---|
| Comments | An ANOVA model with hepatic function group as a fixed effect was fitted to the natural logarithmic transformation of PK parameters (Cmax) for each cohort. | |
| Type of Statistical Test | Other | |
| Comments | Two-sided 90% CIs were calculated for the ratios of GLSMs of PK parameters between moderate hepatic impairment group and the control (normal hepatic function) group. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GLSM ratio |
| Estimated Value | 1.7343 | |
| Confidence Interval |
(2-Sided) 90% 1.2193 to 2.4667 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Cohort 3: Severe Hepatic Impairment, Cohort 3: Normal Hepatic Function |
|---|---|---|
| Comments | An ANOVA model with hepatic function group as a fixed effect was fitted to the natural logarithmic transformation of PK parameters (Cmax) for each cohort. | |
| Type of Statistical Test | Other | |
| Comments | Two-sided 90% CIs were calculated for the ratios of GLSMs of PK parameters between severe hepatic impairment group and the control (normal hepatic function) group. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GLSM ratio |
| Estimated Value | 2.5369 | |
| Confidence Interval |
(2-Sided) 90% 1.7562 to 3.6648 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | PK Parameter: %AUCexp of Cilofexor |
|---|---|
| Description | %AUCexp is defined as the percentage of AUC extrapolated between AUClast and AUCinf. |
| Time Frame | ≤ 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Cohort 1: Mild Hepatic Impairment | Cohort 1: Normal Hepatic Function | Cohort 2: Moderate Hepatic Impairment | Cohort 2: Normal Hepatic Function | Cohort 3: Severe Hepatic Impairment | Cohort 3: Normal Hepatic Function |
|---|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. | 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. |
| Measure Participants | 10 | 10 | 10 | 10 | 10 | 10 |
| Mean (Standard Deviation) [percentage of AUCexp] |
0.63
(0.270)
|
1.95
(1.621)
|
0.64
(0.194)
|
1.87
(1.653)
|
1.81
(1.874)
|
2.96
(1.962)
|
| Title | PK Parameter: Clast of Cilofexor |
|---|---|
| Description | Clast is defined as the last observable concentration of drug. |
| Time Frame | ≤ 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Cohort 1: Mild Hepatic Impairment | Cohort 1: Normal Hepatic Function | Cohort 2: Moderate Hepatic Impairment | Cohort 2: Normal Hepatic Function | Cohort 3: Severe Hepatic Impairment | Cohort 3: Normal Hepatic Function |
|---|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. | 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. |
| Measure Participants | 10 | 10 | 10 | 10 | 10 | 10 |
| Mean (Standard Deviation) [ng/mL] |
1.97
(1.005)
|
3.84
(2.162)
|
2.76
(3.377)
|
3.73
(2.378)
|
6.03
(8.044)
|
2.18
(1.387)
|
| Title | PK Parameter: Tmax of Cilofexor |
|---|---|
| Description | Tmax is defined as the time (observed time point) of Cmax. |
| Time Frame | ≤ 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Cohort 1: Mild Hepatic Impairment | Cohort 1: Normal Hepatic Function | Cohort 2: Moderate Hepatic Impairment | Cohort 2: Normal Hepatic Function | Cohort 3: Severe Hepatic Impairment | Cohort 3: Normal Hepatic Function |
|---|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. | 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. |
| Measure Participants | 10 | 10 | 10 | 10 | 10 | 10 |
| Median (Inter-Quartile Range) [hours] |
3.75
|
3.00
|
4.50
|
3.75
|
5.00
|
4.00
|
| Title | PK Parameter: Tlast of Cilofexor |
|---|---|
| Description | Tlast is defined as the time (observed time point) of Clast. |
| Time Frame | ≤ 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Cohort 1: Mild Hepatic Impairment | Cohort 1: Normal Hepatic Function | Cohort 2: Moderate Hepatic Impairment | Cohort 2: Normal Hepatic Function | Cohort 3: Severe Hepatic Impairment | Cohort 3: Normal Hepatic Function |
|---|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. | 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. |
| Measure Participants | 10 | 10 | 10 | 10 | 10 | 10 |
| Median (Inter-Quartile Range) [hours] |
64.80
|
48.00
|
72.00
|
48.00
|
96.00
|
48.00
|
| Title | PK Parameter: λz of Cilofexor |
|---|---|
| Description | 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. |
| Time Frame | ≤ 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Cohort 1: Mild Hepatic Impairment | Cohort 1: Normal Hepatic Function | Cohort 2: Moderate Hepatic Impairment | Cohort 2: Normal Hepatic Function | Cohort 3: Severe Hepatic Impairment | Cohort 3: Normal Hepatic Function |
|---|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. | 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. |
| Measure Participants | 10 | 10 | 10 | 10 | 10 | 10 |
| Mean (Standard Deviation) [1/hour] |
0.070
(0.0377)
|
0.099
(0.0661)
|
0.051
(0.0152)
|
0.100
(0.0655)
|
0.045
(0.0117)
|
0.099
(0.0659)
|
| Title | PK Parameter: CL/F of Cilofexor |
|---|---|
| Description | CL/F is defined as the apparent oral clearance following administration of the drug. |
| Time Frame | ≤ 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Cohort 1: Mild Hepatic Impairment | Cohort 1: Normal Hepatic Function | Cohort 2: Moderate Hepatic Impairment | Cohort 2: Normal Hepatic Function | Cohort 3: Severe Hepatic Impairment | Cohort 3: Normal Hepatic Function |
|---|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. | 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. |
| Measure Participants | 10 | 10 | 10 | 10 | 10 | 10 |
| Mean (Standard Deviation) [mL/h] |
6621.5
(3219.50)
|
11324.4
(4184.32)
|
5264.4
(2686.26)
|
11631.7
(3666.25)
|
1963.1
(964.19)
|
11535.9
(4627.39)
|
| Title | PK Parameter: Vz/F of Cilofexor |
|---|---|
| Description | Vz/F is defined as the apparent volume of distribution of the drug. |
| Time Frame | ≤ 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Cohort 1: Mild Hepatic Impairment | Cohort 1: Normal Hepatic Function | Cohort 2: Moderate Hepatic Impairment | Cohort 2: Normal Hepatic Function | Cohort 3: Severe Hepatic Impairment | Cohort 3: Normal Hepatic Function |
|---|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. | 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. |
| Measure Participants | 10 | 10 | 10 | 10 | 10 | 10 |
| Mean (Standard Deviation) [mL] |
97797.6
(18500.74)
|
148898.5
(81520.19)
|
99541.7
(31192.41)
|
153854.9
(83844.37)
|
41375.1
(11767.71)
|
160423.9
(92259.03)
|
| Title | PK Parameter: t1/2 of Cilofexor |
|---|---|
| Description | t1/2 is defined as the estimate of the terminal elimination half-life of the drug. |
| Time Frame | ≤ 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Cohort 1: Mild Hepatic Impairment | Cohort 1: Normal Hepatic Function | Cohort 2: Moderate Hepatic Impairment | Cohort 2: Normal Hepatic Function | Cohort 3: Severe Hepatic Impairment | Cohort 3: Normal Hepatic Function |
|---|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. | 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. |
| Measure Participants | 10 | 10 | 10 | 10 | 10 | 10 |
| Median (Inter-Quartile Range) [hours] |
11.45
|
9.49
|
13.53
|
8.12
|
15.90
|
9.31
|
| Title | Percentage of Participants Experiencing Treatment-Emergent Adverse Events |
|---|---|
| Description | |
| Time Frame | Day 1 up to Day 31 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Safety Analysis Set included all participants who took at least 1 dose of study drug. |
| Arm/Group Title | Cohort 1: Mild Hepatic Impairment | Cohort 2: Moderate Hepatic Impairment | Cohort 1 and 2: Normal Hepatic Function | Cohort 3: Severe Hepatic Impairment | Cohort 3: Normal Hepatic Function |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. |
| Measure Participants | 10 | 10 | 16 | 10 | 10 |
| Number [percentage of participants] |
10.0
100%
|
20.0
200%
|
12.5
78.1%
|
30.0
300%
|
0
0%
|
| Title | Percentage of Participants Who Experienced Graded Laboratory Abnormalities |
|---|---|
| Description | 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. |
| Time Frame | Day 1 up to Day 31 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set were analyzed. |
| Arm/Group Title | Cohort 1: Mild Hepatic Impairment | Cohort 2: Moderate Hepatic Impairment | Cohort 1 and 2: Normal Hepatic Function | Cohort 3: Severe Hepatic Impairment | Cohort 3: Normal Hepatic Function |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. |
| Measure Participants | 10 | 10 | 16 | 10 | 10 |
| Any Laboratory Abnormality |
90.0
900%
|
100.0
1000%
|
50.0
312.5%
|
100.0
1000%
|
60.0
600%
|
| Grade 3 or above Laboratory Abnormalities |
20.0
200%
|
20.0
200%
|
0
0%
|
40.0
400%
|
0
0%
|
| Title | Pharmacodynamic (PD) Parameter: Mean Day 1/ Day -1 Ratio of AUC2-12 for α-hydroxy-4-cholesten-3-one (C4) |
|---|---|
| Description | 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. |
| Time Frame | 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 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Cohort 1: Mild Hepatic Impairment | Cohort 1: Normal Hepatic Function | Cohort 2: Moderate Hepatic Impairment | Cohort 2: Normal Hepatic Function | Cohort 3: Severe Hepatic Impairment | Cohort 3: Normal Hepatic Function |
|---|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. | 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. |
| Measure Participants | 10 | 10 | 10 | 10 | 10 | 10 |
| Mean (Standard Deviation) [ratio] |
0.706
(0.2273)
|
0.817
(0.2836)
|
0.716
(0.2370)
|
0.681
(0.2614)
|
1.063
(0.2469)
|
0.978
(0.4155)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Mild Hepatic Impairment, Cohort 1: Normal Hepatic Function |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | Two-sided 90% CIs were calculated for the ratios of GLSMs of PD parameters between mild hepatic impairment group and the control (normal hepatic function) group. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GLSM ratio |
| Estimated Value | 0.8722 | |
| Confidence Interval |
(2-Sided) 90% 0.6827 to 1.1144 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: Moderate Hepatic Impairment, Cohort 2: Normal Hepatic Function |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | Two-sided 90% CIs were calculated for the ratios of GLSMs of PD parameters between moderate hepatic impairment group and the control (normal hepatic function) group. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GLSM ratio |
| Estimated Value | 1.0731 | |
| Confidence Interval |
(2-Sided) 90% 0.8295 to 1.3883 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Cohort 3: Severe Hepatic Impairment, Cohort 3: Normal Hepatic Function |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | Two-sided 90% CIs were calculated for the ratios of GLSMs of PD parameters between severe hepatic impairment group and the control (normal hepatic function) group. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GLSM ratio |
| Estimated Value | 1.1475 | |
| Confidence Interval |
(2-Sided) 90% 0.8783 to 1.4992 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | PD Parameter: Mean Day 1/ Day -1 Ratio of Cmin for α-hydroxy-4-cholesten-3-one (C4) |
|---|---|
| Description | 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. |
| Time Frame | 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 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Cohort 1: Mild Hepatic Impairment | Cohort 1: Normal Hepatic Function | Cohort 2: Moderate Hepatic Impairment | Cohort 2: Normal Hepatic Function | Cohort 3: Severe Hepatic Impairment | Cohort 3: Normal Hepatic Function |
|---|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. | 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. |
| Measure Participants | 10 | 10 | 10 | 10 | 10 | 10 |
| Mean (Standard Deviation) [ratio] |
0.599
(0.3272)
|
0.707
(0.2838)
|
0.668
(0.2384)
|
0.583
(0.1634)
|
0.953
(0.2073)
|
0.727
(0.2674)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Mild Hepatic Impairment, Cohort 1: Normal Hepatic Function |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | Two-sided 90% CIs were calculated for the ratios of GLSMs of PD parameters between mild hepatic impairment group and the control (normal hepatic function) group. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GLSM ratio |
| Estimated Value | 0.8188 | |
| Confidence Interval |
(2-Sided) 90% 0.5837 to 1.1486 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: Moderate Hepatic Impairment, Cohort 2: Normal Hepatic Function |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | Two-sided 90% CIs were calculated for the ratios of GLSMs of PD parameters between moderate hepatic impairment group and the control (normal hepatic function) group. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GLSM ratio |
| Estimated Value | 1.1323 | |
| Confidence Interval |
(2-Sided) 90% 0.8772 to 1.4615 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Cohort 3: Severe Hepatic Impairment, Cohort 3: Normal Hepatic Function |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | Two-sided 90% CIs were calculated for the ratios of GLSMs of PD parameters between severe hepatic impairment group and the control (normal hepatic function) group. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GLSM ratio |
| Estimated Value | 1.3563 | |
| Confidence Interval |
(2-Sided) 90% 1.0468 to 1.7574 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | PD Parameter: Mean Day 1/ Day -1 Ratio of AUC2-12 for Fibroblast Growth Factor 19 (FGF19) |
|---|---|
| Description | 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. |
| Time Frame | 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 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Cohort 1: Mild Hepatic Impairment | Cohort 1: Normal Hepatic Function | Cohort 2: Moderate Hepatic Impairment | Cohort 2: Normal Hepatic Function | Cohort 3: Severe Hepatic Impairment | Cohort 3: Normal Hepatic Function |
|---|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. | 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. |
| Measure Participants | 10 | 10 | 10 | 10 | 10 | 10 |
| Mean (Standard Deviation) [ratio] |
3.031
(1.0376)
|
2.840
(0.9254)
|
3.730
(1.3768)
|
2.848
(1.0250)
|
1.582
(0.8182)
|
2.179
(1.6972)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Mild Hepatic Impairment, Cohort 1: Normal Hepatic Function |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | Two-sided 90% CIs were calculated for the ratios of GLSMs of PD parameters between mild hepatic impairment group and the control (normal hepatic function) group. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GLSM ratio |
| Estimated Value | 1.0658 | |
| Confidence Interval |
(2-Sided) 90% 0.8275 to 1.3726 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: Moderate Hepatic Impairment, Cohort 2: Normal Hepatic Function |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | Two-sided 90% CIs were calculated for the ratios of GLSMs of PD parameters between moderate hepatic impairment group and the control (normal hepatic function) group. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GLSM ratio |
| Estimated Value | 1.2942 | |
| Confidence Interval |
(2-Sided) 90% 0.9663 to 1.7334 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Cohort 3: Severe Hepatic Impairment, Cohort 3: Normal Hepatic Function |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | Two-sided 90% CIs were calculated for the ratios of GLSMs of PD parameters between severe hepatic impairment group and the control (normal hepatic function) group. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GLSM ratio |
| Estimated Value | 0.8225 | |
| Confidence Interval |
(2-Sided) 90% 0.5479 to 1.2347 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | PD Parameter: Mean Day 1/ Day -1 Ratio of Cmax for Fibroblast Growth Factor 19 (FGF19) |
|---|---|
| Description | 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. |
| Time Frame | 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 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Cohort 1: Mild Hepatic Impairment | Cohort 1: Normal Hepatic Function | Cohort 2: Moderate Hepatic Impairment | Cohort 2: Normal Hepatic Function | Cohort 3: Severe Hepatic Impairment | Cohort 3: Normal Hepatic Function |
|---|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. | 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. |
| Measure Participants | 10 | 10 | 10 | 10 | 10 | 10 |
| Mean (Standard Deviation) [ratio] |
3.778
(1.4954)
|
3.494
(1.4423)
|
4.459
(1.9899)
|
3.145
(1.4484)
|
1.899
(1.1619)
|
2.098
(1.1579)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Mild Hepatic Impairment, Cohort 1: Normal Hepatic Function |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | Two-sided 90% CIs were calculated for the ratios of GLSMs of PD parameters between mild hepatic impairment group and the control (normal hepatic function) group. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GLSM ratio |
| Estimated Value | 1.0806 | |
| Confidence Interval |
(2-Sided) 90% 0.7910 to 1.4762 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: Moderate Hepatic Impairment, Cohort 2: Normal Hepatic Function |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | Two-sided 90% CIs were calculated for the ratios of GLSMs of PD parameters between moderate hepatic impairment group and the control (normal hepatic function) group. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GLSM ratio |
| Estimated Value | 1.3729 | |
| Confidence Interval |
(2-Sided) 90% 0.9663 to 1.9506 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Cohort 3: Severe Hepatic Impairment, Cohort 3: Normal Hepatic Function |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | Two-sided 90% CIs were calculated for the ratios of GLSMs of PD parameters between severe hepatic impairment group and the control (normal hepatic function) group. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GLSM ratio |
| Estimated Value | 0.9030 | |
| Confidence Interval |
(2-Sided) 90% 0.6142 to 1.3275 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | Day 1 up to Day 31 | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | The Safety Analysis Set included all participants who took at least 1 dose of study drug. | |||||||||
| Arm/Group Title | Cohort 1: Mild Hepatic Impairment | Cohort 2: Moderate Hepatic Impairment | Cohort 1 and 2: Normal Hepatic Function | Cohort 3: Severe Hepatic Impairment | Cohort 3: Normal Hepatic Function | |||||
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. | |||||
All Cause Mortality |
||||||||||
| Cohort 1: Mild Hepatic Impairment | Cohort 2: Moderate Hepatic Impairment | Cohort 1 and 2: Normal Hepatic Function | Cohort 3: Severe Hepatic Impairment | Cohort 3: Normal Hepatic Function | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/10 (0%) | 0/10 (0%) | 0/16 (0%) | 0/10 (0%) | 0/10 (0%) | |||||
Serious Adverse Events |
||||||||||
| Cohort 1: Mild Hepatic Impairment | Cohort 2: Moderate Hepatic Impairment | Cohort 1 and 2: Normal Hepatic Function | Cohort 3: Severe Hepatic Impairment | Cohort 3: Normal Hepatic Function | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/10 (0%) | 1/10 (10%) | 0/16 (0%) | 1/10 (10%) | 0/10 (0%) | |||||
| Gastrointestinal disorders | ||||||||||
| Gastrointestinal haemorrhage | 0/10 (0%) | 1/10 (10%) | 0/16 (0%) | 0/10 (0%) | 0/10 (0%) | |||||
| Upper gastrointestinal haemorrhage | 0/10 (0%) | 0/10 (0%) | 0/16 (0%) | 1/10 (10%) | 0/10 (0%) | |||||
Other (Not Including Serious) Adverse Events |
||||||||||
| Cohort 1: Mild Hepatic Impairment | Cohort 2: Moderate Hepatic Impairment | Cohort 1 and 2: Normal Hepatic Function | Cohort 3: Severe Hepatic Impairment | Cohort 3: Normal Hepatic Function | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/10 (10%) | 1/10 (10%) | 2/16 (12.5%) | 2/10 (20%) | 0/10 (0%) | |||||
| Gastrointestinal disorders | ||||||||||
| Dyspepsia | 0/10 (0%) | 1/10 (10%) | 0/16 (0%) | 0/10 (0%) | 0/10 (0%) | |||||
| Injury, poisoning and procedural complications | ||||||||||
| Skin abrasion | 0/10 (0%) | 0/10 (0%) | 0/16 (0%) | 1/10 (10%) | 0/10 (0%) | |||||
| Musculoskeletal and connective tissue disorders | ||||||||||
| Arthralgia | 0/10 (0%) | 0/10 (0%) | 0/16 (0%) | 1/10 (10%) | 0/10 (0%) | |||||
| Back pain | 0/10 (0%) | 0/10 (0%) | 1/16 (6.3%) | 0/10 (0%) | 0/10 (0%) | |||||
| Nervous system disorders | ||||||||||
| Headache | 0/10 (0%) | 0/10 (0%) | 1/16 (6.3%) | 0/10 (0%) | 0/10 (0%) | |||||
| Vascular disorders | ||||||||||
| Haematoma | 1/10 (10%) | 0/10 (0%) | 0/16 (0%) | 0/10 (0%) | 0/10 (0%) | |||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or The study has been completed at all study sites for at least 2 years
Results Point of Contact
| Name/Title | Gilead Clinical Study Information Center |
|---|---|
| Organization | Gilead Sciences |
| Phone | 1-833-445-3230 (GILEAD-0) |
| GileadClinicalTrials@gilead.com |
Responsible Party:
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT02808312
Other Study ID Numbers:
- GS-US-402-3885
First Posted:
Jun 21, 2016
Last Update Posted:
Jan 7, 2021
Last Verified:
Dec 1, 2020