Phase 1
N=57
Pharmacokinetics and Pharmacodynamics of Cilofexor in Adults With Normal and Impaired Hepatic Function
Nonalcoholic Steatohepatitis (NASH) · Primary Sclerosing Cholangitis (PSC)
Bottom Line
View on ClinicalTrials.gov: NCT02808312 ↗Enrolled (actual)
57
Serious AEs
3.6%
Results posted
Sep 2020
Primary outcome: Primary: Pharmacokinetic (PK) Parameter: AUClast of Cilofexor — 5381.0; 2972.6; 8223.7; 2756.7 h*ng/mL
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Cilofexor (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Gilead Sciences
- Primary completion
- Oct 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Pharmacokinetic (PK) Parameter: AUClast of Cilofexor |
5381.0; 2972.6; 8223.7; 2756.7; 6534.3; 960.0 | — |
| PRIMARY PK Parameter: AUCinf of Cilofexor |
5411.9; 3024.3; 8288.2; 2805.6; 6719.4; 986.2 | — |
| PRIMARY PK Parameter: Cmax of Cilofexor |
994.1; 603.5; 909.2; 495.7; 426.6; 182.4 | — |
| PRIMARY PK Parameter: %AUCexp of Cilofexor |
0.63; 1.95; 0.64; 1.87; 1.81; 2.96 | — |
| PRIMARY PK Parameter: Clast of Cilofexor |
1.97; 3.84; 2.76; 3.73; 6.03; 2.18 | — |
| PRIMARY PK Parameter: Tmax of Cilofexor |
3.75; 3.00; 4.50; 3.75; 5.00; 4.00 | — |
| PRIMARY PK Parameter: Tlast of Cilofexor |
64.80; 48.00; 72.00; 48.00; 96.00; 48.00 | — |
| PRIMARY PK Parameter: λz of Cilofexor |
0.070; 0.099; 0.051; 0.100; 0.045; 0.099 | — |
| PRIMARY PK Parameter: CL/F of Cilofexor |
6621.5; 11324.4; 5264.4; 11631.7; 1963.1; 11535.9 | — |
| PRIMARY PK Parameter: Vz/F of Cilofexor |
97797.6; 148898.5; 99541.7; 153854.9; 41375.1; 160423.9 | — |
| PRIMARY PK Parameter: t1/2 of Cilofexor |
11.45; 9.49; 13.53; 8.12; 15.90; 9.31 | — |
| SECONDARY Percentage of Participants Experiencing Treatment-Emergent Adverse Events |
10.0; 20.0; 12.5; 30.0; 0 | — |
| SECONDARY Percentage of Participants Who Experienced Graded Laboratory Abnormalities |
90.0; 100.0; 50.0; 100.0; 60.0; 20.0 | — |
| SECONDARY Pharmacodynamic (PD) Parameter: Mean Day 1/ Day -1 Ratio of AUC2-12 for α-hydroxy-4-cholesten-3-one (C4) |
0.706; 0.817; 0.716; 0.681; 1.063; 0.978 | — |
| SECONDARY PD Parameter: Mean Day 1/ Day -1 Ratio of Cmin for α-hydroxy-4-cholesten-3-one (C4) |
0.599; 0.707; 0.668; 0.583; 0.953; 0.727 | — |
| SECONDARY PD Parameter: Mean Day 1/ Day -1 Ratio of AUC2-12 for Fibroblast Growth Factor 19 (FGF19) |
3.031; 2.840; 3.730; 2.848; 1.582; 2.179 | — |
| SECONDARY PD Parameter: Mean Day 1/ Day -1 Ratio of Cmax for Fibroblast Growth Factor 19 (FGF19) |
3.778; 3.494; 4.459; 3.145; 1.899; 2.098 | — |
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.
Eligibility Criteria
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.
Data sourced from ClinicalTrials.gov (NCT02808312). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.