Ubrogepant for the Acute Treatment of Migraine: Pooled Efficacy, Safety, and Tolerability From the ACHIEVE I and ACHIEVE II Phase 3 Randomized Trials

Abstract

Introduction: Ubrogepant is an oral, small-molecule calcitonin gene-related peptide receptor antagonist approved for the acute treatment of migraine. The efficacy and safety of ubrogepant were demonstrated in two pivotal phase 3, single-attack, randomized, placebo-controlled trials (ACHIEVE I and ACHIEVE II).

Methods: We conducted a post hoc analysis of pooled data from the ACHIEVE trials to evaluate the efficacy, safety, and tolerability of ubrogepant 50 mg (the only dose evaluated in both trials) versus placebo across a large population of participants with migraine. The coprimary efficacy outcomes were pain freedom and absence of the most bothersome migraine-associated symptom (including photophobia, phonophobia, and nausea) at 2 h post dose. Secondary outcomes included pain relief at 2 h post dose, sustained pain relief and pain freedom from 2 to 24 h, and absence of specific migraine-associated symptoms at 2 h post dose.

Results: A total of 2240 eligible participants were randomized to placebo (n = 1122) or ubrogepant 50 mg (n = 1118) in the ACHIEVE trials. Pain freedom at 2 h was reported in 13.0% of participants in the pooled placebo group and 20.5% in the pooled ubrogepant 50 mg group (odds ratio [OR] 1.72; 95% confidence interval [CI] 1.34, 2.22; P < 0.001). Absence of the most bothersome migraine-associated symptom at 2 h was reported by 27.6% in the pooled placebo group and by 38.7% in the pooled ubrogepant 50 mg group (OR 1.68; 95% CI 1.37, 2.05; P < 0.001). Adverse events (AEs) within 48 h after the initial or optional second dose were reported by 11.5 and 11.2% of participants in the pooled placebo and pooled ubrogepant 50 mg groups, respectively. The most common AE was nausea (1.8 and 1.9%, respectively). No serious AEs related to treatment or discontinuations due to AEs were reported.

Conclusion: These results further support the efficacy, safety, and tolerability of ubrogepant for the acute treatment of migraine.

Trial registration: ClinicalTrials.gov Identifiers: ACHIEVE I: NCT02828020; ACHIEVE II: NCT02867709.

Keywords: Calcitonin gene–related peptide; Gepant; Headache; Migraine; Ubrogepant.

Figures

Fig. 1

CONSORT flow diagram of the pooled analysis of ACHIEVE I and ACHIEVE II. a The mITT population included all randomized participants who received at least one dose of the study medication, recorded baseline migraine headache severity, and reported at least one post-dose migraine headache severity rating or migraine-associated symptom outcome at or before 2 h after the initial dose. mITT Modified intent-to-treat

Fig. 2

Pooled efficacy results. Percentage of participants reporting pain freedom (a) and absence of the most bothersome migraine-associated symptom (b) at 2 h post dose in the pooled placebo and pooled ubrogepant 50 mg groups from ACHIEVE I and ACHIEVE II

Fig. 3

Pooled efficacy results. Percentage of participants reporting pain relief at 2 h post dose (a) and the rate of sustained pain relief from 2 to 24 h and 2 to 48 h post dose (b) in the pooled placebo and pooled ubrogepant 50 mg groups from ACHIEVE I and ACHIEVE II

Fig. 4

Absence of migraine-associated symptoms at 2 h post dose. Percentage of participants reporting absence of photophobia (a), phonophobia (b), and nausea (c) in the pooled placebo (n = 912) and pooled ubrogepant 50 mg (n = 887) groups from ACHIEVE I and ACHIEVE II

Fig. 5

Efficacy of a second dose. Percentage of participants reporting pain freedom 2 h after a second dose of ubrogepant 50 mg versus placebo in the 353 participants in the pooled ubrogepant 50 mg group who opted to take a second dose of study medication