Evaluation of the Pharmacokinetic Interaction and Safety of Ubrogepant Coadministered With Esomeprazole Magnesium

Abstract Ubrogepant is a calcitonin gene–related peptide receptor antagonist for the acute treatment of migraine. Esomeprazole magnesium increases intragastric pH, which may affect oral ubrogepant absorption. This open‐label, nonrandomized, crossover trial evaluated esomeprazole magnesium's impact on the pharmacokinetics and safety of coadministered ubrogepant in healthy adults. Participants received ubrogepant 100 mg on day 1, esomeprazole magnesium 40 mg on days 9 to 13, and ubrogepant 100 mg with esomeprazole magnesium 40 mg on day 14. No effect on ubrogepant pharmacokinetics was concluded if 90% confidence intervals of geometric mean ratios were within 80% to 125% for comparison of pharmacokinetic parameters between ubrogepant + esomeprazole magnesium versus ubrogepant alone. Thirty participants enrolled (mean age, 31.7 years; 53.3% males). Ubrogepant peak plasma concentration (C max ) decreased 23%, time to C max increased by 1.5 hours, and area under the plasma concentration‐time curve was reduced by ≈10% when coadministered with esomeprazole magnesium versus ubrogepant alone. The 90% confidence interval of the geometric mean ratio for C max did not fall within the 80% to 125% equivalence range, but the decrease was not considered clinically meaningful. Esomeprazole magnesium coadministered with ubrogepant did not increase the incidence rate of treatment‐emergent adverse events, and interactions between the medications are likely to have limited clinical relevance.