Summary:
In healthy adult participants, including Japanese and non-Japanese individuals, single-dose administration of cilofexor and firsocostat significantly resulted in higher plasma exposure in Japanese participants compared to non-Japanese participants compared to pharmacokinetic analysis of non-Japanese participants under identical conditions. Both drugs were well tolerated, with no notable differences in adverse events or laboratory abnormalities, and no need for dose adjustments despite higher exposure.
| PICO | Description |
|---|---|
| Population | Healthy adult participants, including Japanese (n = 20 for the cilofexor study and n = 21 for the firsocostat study) and non-Japanese participants (n = 20 for the cilofexor study and n = 21 for the firsocostat study). Total participants who completed each study: 39. |
| Intervention | Administration of cilofexor (100 mg) and firsocostat (20 mg) as a single dose to assess pharmacokinetics and safety over 96 hours with intensive pharmacokinetic sampling performed. |
| Comparison | Plasma exposures of cilofexor and firsocostat were compared across Japanese and non-Japanese participants using the area under the concentration-time curve (AUC) from time 0 to infinity (AUCinf). Exposure for cilofexor was 1.24-fold higher and for firsocostat 1.98-fold higher in Japanese participants compared to non-Japanese. |
| Outcome | Both cilofexor and firsocostat were well tolerated, with no notable differences in adverse events or laboratory abnormalities between Japanese and non-Japanese participants. The approximate 2-fold higher exposure of firsocostat in Japanese participants does not necessitate dose reduction, as prior trials established safety for higher doses (up to 200 mg daily). |
Source: Islam R Younis, et al. “Pharmacokinetics and Safety of Cilofexor and Firsocostat in Healthy Japanese and Non-Japanese Participants.” Journal of Clinical Pharmacology, 2024. Read article here.
