| Primary | Pharmacokinetic (PK) Parameter: AUClast of Cilofexor | AUClast is defined as the concentration of drug from time zero to the last observable concentration. | 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. | Posted | | Mean | Standard Deviation | h*ng/mL | | ≤ 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 | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | Cohort 1: Normal Hepatic Function | 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. | | OG002 | 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. | | OG003 | Cohort 2: Normal Hepatic Function | 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. | | OG004 | 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. | | OG005 | 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. |
| | Units | Counts |
|---|
| Participants | - OG00010
- OG00110
- OG00210
- OG003
|
| | Title | Denominators | Categories |
|---|
| | | Title | Measurements |
|---|
| - OG0005381.0± 2175.34
- OG0012972.6± 1230.49
- OG0028223.7± 7492.41
- OG003
|
|
| | Group IDs | Group Description | Statistical Method | Statistical Comment | P-Value | P-Value Comment | Parameter Type | Parameter Value | Dispersion Type | Dispersion Value | Confidence Interval Sides | Confidence Interval % | CI Lower Limit | CI Upper Limit | CI Lower Limit Comment | CI Upper Limit Comment | Estimate Comment | Tested Non-Inferiority | Non-Inferiority Type | Non-Inferiority Comment | Other Analysis Description |
|---|
| 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. | | | | | GLSM ratio | 1.7869 | | | 2-Sided | 90 | 1.2885 | 2.4781 | | | | | Other | 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. | |
|
| Primary | PK Parameter: AUCinf of Cilofexor | AUCinf is defined as the concentration of drug extrapolated to infinite time. | 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. | Posted | | Mean | Standard Deviation | h*ng/mL | | ≤ 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 | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | Cohort 1: Normal Hepatic Function | 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. | | OG002 | 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. | | OG003 |
|
| Primary | PK Parameter: Cmax of Cilofexor | Cmax is defined as the maximum concentration of drug. | 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. | Posted | | Mean | Standard Deviation | ng/mL | | ≤ 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 | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | Cohort 1: Normal Hepatic Function | 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. | | OG002 | 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. | | OG003 | Cohort 2: Normal Hepatic Function |
|
| Primary | PK Parameter: %AUCexp of Cilofexor | %AUCexp is defined as the percentage of AUC extrapolated between AUClast and AUCinf. | 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. | Posted | | Mean | Standard Deviation | percentage of AUCexp | | ≤ 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 | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | Cohort 1: Normal Hepatic Function | 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. | | OG002 | 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. | | OG003 |
|
| Primary | PK Parameter: Clast of Cilofexor | Clast is defined as the last observable concentration of drug. | 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. | Posted | | Mean | Standard Deviation | ng/mL | | ≤ 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 | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | Cohort 1: Normal Hepatic Function | 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. | | OG002 | 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. | | OG003 |
|
| Primary | PK Parameter: Tmax of Cilofexor | Tmax is defined as the time (observed time point) of Cmax. | 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. | Posted | | Median | Inter-Quartile Range | hours | | ≤ 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 | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | Cohort 1: Normal Hepatic Function | 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. | | OG002 | 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. | | OG003 |
|
| Primary | PK Parameter: Tlast of Cilofexor | Tlast is defined as the time (observed time point) of Clast. | 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. | Posted | | Median | Inter-Quartile Range | hours | | ≤ 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 | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | Cohort 1: Normal Hepatic Function | 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. | | OG002 | 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. | | OG003 |
|
| Primary | PK Parameter: λz of Cilofexor | 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. | 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. | Posted | | Mean | Standard Deviation | 1/hour | | ≤ 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 | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | Cohort 1: Normal Hepatic Function | 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. | | OG002 | 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. |
|
| Primary | PK Parameter: CL/F of Cilofexor | CL/F is defined as the apparent oral clearance following administration of the drug. | 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. | Posted | | Mean | Standard Deviation | mL/h | | ≤ 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 | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | Cohort 1: Normal Hepatic Function | 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. | | OG002 | 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. | | OG003 |
|
| Primary | PK Parameter: Vz/F of Cilofexor | Vz/F is defined as the apparent volume of distribution of the drug. | 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. | Posted | | Mean | Standard Deviation | mL | | ≤ 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 | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | Cohort 1: Normal Hepatic Function | 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. | | OG002 | 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. | | OG003 |
|
| Primary | PK Parameter: t1/2 of Cilofexor | t1/2 is defined as the estimate of the terminal elimination half-life of the drug. | 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. | Posted | | Median | Inter-Quartile Range | hours | | ≤ 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 | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | Cohort 1: Normal Hepatic Function | 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. | | OG002 | 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. | | OG003 |
|
| Secondary | Percentage of Participants Experiencing Treatment-Emergent Adverse Events | | The Safety Analysis Set included all participants who took at least 1 dose of study drug. | Posted | | Number | | percentage of participants | | Day 1 up to Day 31 | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | 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. | | OG002 | Cohort 1 and 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. | | OG003 | 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. |
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| Secondary | Percentage of Participants Who Experienced Graded Laboratory Abnormalities | 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. | Participants in the Safety Analysis Set were analyzed. | Posted | | Number | | percentage of participants | | Day 1 up to Day 31 | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | 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. | | OG002 | Cohort 1 and 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. | |
|
| Secondary | Pharmacodynamic (PD) Parameter: Mean Day 1/ Day -1 Ratio of AUC2-12 for α-hydroxy-4-cholesten-3-one (C4) | 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. | 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. | Posted | | Mean | Standard Deviation | ratio | | 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 | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | Cohort 1: Normal Hepatic Function | 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. | | OG002 | Cohort 2: Moderate Hepatic Impairment |
|
| Secondary | PD Parameter: Mean Day 1/ Day -1 Ratio of Cmin for α-hydroxy-4-cholesten-3-one (C4) | 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. | 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. | Posted | | Mean | Standard Deviation | ratio | | 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 | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | Cohort 1: Normal Hepatic Function | 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. | | OG002 | Cohort 2: Moderate Hepatic Impairment | |
|
| Secondary | PD Parameter: Mean Day 1/ Day -1 Ratio of AUC2-12 for Fibroblast Growth Factor 19 (FGF19) | 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. | 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. | Posted | | Mean | Standard Deviation | ratio | | 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 | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | Cohort 1: Normal Hepatic Function | 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. | | OG002 | Cohort 2: Moderate Hepatic Impairment |
|
| Secondary | PD Parameter: Mean Day 1/ Day -1 Ratio of Cmax for Fibroblast Growth Factor 19 (FGF19) | 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. | 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. | Posted | | Mean | Standard Deviation | ratio | | 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 | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | Cohort 1: Normal Hepatic Function | 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. | | OG002 | Cohort 2: Moderate Hepatic Impairment | |
|