Phase 1
Completed N=120
Study in Healthy Volunteers to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GS-9674 (Cilofexor), and the Effect of Food on GS-9674 Pharmacokinetics and Pharmacodynamics
Nonalcoholic Steatohepatitis (NASH)
Source: ClinicalTrials.gov NCT02654002 ↗
Enrolled (actual)
120
Serious AEs
0.0%
Results posted
Oct 2020
Primary outcomePrimary: Single-Dose Pharmacokinetic (PK) Parameter: AUClast of Cilofexor — 1236.0; 2450.6; 7712.1; 12458.8 hours*nanogram/millilitre (h*ng/mL)
Summary
This study will evaluate the safety and tolerability of escalating single- and multiple-oral doses of cilofexor, and characterize the single- and multiple-dose pharmacokinetics (PK) of cilofexor. The study will be conducted in 3 parts (Part A, Part B, and Part C). Participants will receive either cilofexor or cilofexor placebo.
Part A will proceed in 4 prespecified staggered cohorts. Within each cohort, the cumulative, blinded safety data will be evaluated for dose escalation from single-dose (Period 1) to multiple-dose (Period 2). Based on the available safety, pharmacokinetics, and/or pharmacodynamics (PD) data from cohorts in Part A and Part C (if applicable), total daily doses and frequency of dosing will be chosen for the cohorts in Part B. Parts B and C will consist of adaptive cohorts and may be initiated in parallel. Part B cohorts may be initiated in parallel with cohorts in Part A if the total dose under evaluation is at or below a dose already evaluated.
This study is partially blinded (no one is blinded on Day -1).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Single-Dose Pharmacokinetic (PK) Parameter: AUClast of Cilofexor |
1236.0; 2450.6; 7712.1; 12458.8; 4979.5; 3091.4 | — |
| PRIMARY Single-Dose PK Parameter: AUCinf of Cilofexor |
1255.9; 2473.4; 7743.7; 12495.7; 5016.7; 3559.2 | — |
| PRIMARY Single-Dose PK Parameter: Cmax of Cilofexor |
304.2; 580.2; 2592.3; 3055.5; 927.6; 665.9 | — |
| PRIMARY Multiple-Dose PK Parameter: AUCtau of Cilofexor |
1284.9; 2891.0; 6719.4; 8486.0; 4182.7; 3698.3 | — |
| PRIMARY Multiple-Dose PK Parameter: Cmax of Cilofexor |
322.2; 717.5; 2231.2; 2327.9; 818.7; 697.8 | — |
| PRIMARY Multiple-Dose PK Parameter: Ctau of Cilofexor |
2.7; 7.9; 36.3; 70.1; 22.6; 107.6 | — |
| PRIMARY Percentage of Participants With at Least One Adverse Event (AE) |
33.3; 25.0; 33.3; 25.0; 41.7; 27.3 | — |
| PRIMARY Percentage of Participants With Clinically Significant 12-Lead Electrocardiogram (ECG) Abnormalities |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Percentage of Participants With Clinical Laboratory Abnormalities |
0.0; 8.3; 16.7; 0.0; 0.0; 0.0 | — |
| SECONDARY Pharmacodynamic (PD) Parameter: Fibroblast Growth Factor 19 (FGF19) AUC2-12 Ratio |
2.040; 1.958; 2.037; 2.314; 0.981; 2.406 | — |
| SECONDARY PD Parameter: FGF19 Cmax Ratio |
2.217; 2.084; 2.259; 2.679; 0.982; 2.793 | — |
| SECONDARY PD Parameter: 7alpha-hydroxy-4-cholesten-3-one (C4) AUC2-12 Ratio |
0.681; 0.640; 0.427; 0.347; 1.147; 0.837 | — |
| SECONDARY PD Parameter: C4 Cmin Ratio |
0.715; 0.759; 0.663; 0.467; 1.201; 0.613 | — |
Eligibility Criteria
Key Inclusion Criteria
- Healthy male and non-pregnant, non-lactating female volunteers
- Body mass index (BMI) 19 ≤ BMI ≤ 30 kg/m^2
- Normal 12-lead electrocardiogram (ECG) or one with abnormalities that are considered clinically insignificant by the investigator
- Normal renal function (estimated glomerular filtration rate calculated using the Cockcroft-Gault equation ≥ 80 mL/min)
- No significant medical history, and in good general health as determined by the investigator at screening evaluation performed no more than 28 days prior to the scheduled first dose.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Data sourced from ClinicalTrials.gov (NCT02654002). 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. Informational only — not medical advice.