Abstract A population pharmacokinetic (popPK) model was developed for ubrogepant using data from 10 Phase 1, 1 Phase 2, and 2 Phase 3 studies. The data were described by a 2‐compartment model with linear elimination and transit compartment absorption. Formulation, food intake, race, gender, and hepatic impairment had a statistically significant impact on ubrogepant PK. Significant exposure‐response relationships were found for 2 h pain relief and pain freedom, and 24 h sustained pain relief and sustained pain freedom. Ubrogepant significantly improved the symptoms of phonophobia and photophobia, and the most bothersome migraine symptom, with a modest trend with ubrogepant dose. A Phase 3 study evaluating ubrogepant use during the prodrome was incorporated into the popPK model, and the mean transit time and inter‐individual variability were re‐estimated. Exposure‐response analysis across multiple endpoints in the prodrome study (including absence of moderate/severe headache within 24 or 48 h, absence of headache of any intensity within 24 h, and ability to function normally within 24 h) showed a treatment effect with improved outcomes after receiving ubrogepant.
Stodtmann et al. (Fri,) studied this question.