Food Effects on the Pharmacokinetics of Single Dose and Steady-State Ralinepag, a Novel Oral Prostacyclin Agonist, in Healthy Volunteers.

BACKGROUND

Pulmonary arterial hypertension (PAH) is a rare, progressive disorder characterized by pathological pulmonary vascular remodeling leading to right heart failure. Ralinepag extended-release (XR), is a once-daily oral prostacyclin (IP) receptor to treat PAH. This study evaluated the safety, tolerability, and pharmacokinetics (PK) of multiple ascending doses of ralinepag XR tablets in fed and fasted healthy adult volunteers.

STUDY DESIGN AND

METHODS

A single-center, open-label, nonrandomized, multiple-dose titration study of two cohorts (fed (n = 13) or fasted (n = 15)) with once-daily dosing of ralinepag XR for 5 days, with up to four sequential dose escalations. Dosing began at 60 µg and escalated every 5 days as tolerated (120, 180, 240, and 300 µg). Doses were administered after a 10-h overnight fast or a moderate-fat breakfast. PK parameters assessed were maximum observed concentration (Cmax), area under the concentration-time curve from time 0 to 24 h postdose (AUC(0-24)), and time of maximum observed concentration (Tmax) on day 1 (single 60 μg dose); and Cmax, AUC(0-24), and Tmax at steady state.

RESULTS

Ralinepag XR exhibited minimal differences in PK parameters between fed and fasted states in the first 24 h. Multiple-dose administration showed a dose-dependent increase in exposure and a median 4-10 h Tmax at steady state, independent of fed status. Ralinepag accumulation was approximately 2.1-fold after 5 days of dosing at 60 μg in both fed and fasted states, consistent with a mean half-life of 20-36 h. There were no serious adverse events attributable to ralinepag. The most commonly reported adverse events were headache, jaw pain, and nausea with no differences between groups.

CONCLUSIONS

Food status did not significantly affect the PK or safety of ralinepag XR.