Safety and efficacy of ubrogepant in participants with major cardiovascular risk factors in two single-attack phase 3 randomized trials: ACHIEVE I and II

Susan Hutchinson, Stephen D. Silberstein, Andrew M. Blumenfeld, Richard B. Lipton, Kaifeng Lu, Sung Yun Yu, Lawrence Severt

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: To examine the safety and efficacy of ubrogepant for acute treatment of migraine across cardiovascular (CV) disease risk categories. Methods: ACHIEVE I and II were multicenter, double-blind, single-attack, phase 3 trials in adults with migraine, with or without aura. Participants were randomized 1:1:1 to placebo or ubrogepant (50 or 100 mg in ACHIEVE I; 25 or 50 mg in ACHIEVE II), to treat one migraine attack of moderate or severe headache pain intensity. This post-hoc analysis pooled data from ubrogepant 50 mg and placebo groups from the ACHIEVE trials to examine the safety and efficacy of ubrogepant by baseline cardiovascular disease risk factors. Using a cardiovascular risk assessment algorithm, participants were categorized as having no cardiovascular risk, low cardiovascular risk or moderate-high cardiovascular risk at baseline. Treatment-emergent adverse events were documented 48 h and 30 days after taking the trial medication. Co-primary efficacy outcomes were 2-h pain freedom and 2-h absence of most bothersome migraine-associated symptom. Results: Overall, 3358 participants were randomized in the ACHIEVE trials (n = 2901 safety population; n = 2682 modified intent-to-treat population). In the safety population, 11% of participants were categorized as moderate-high (n = 311), 32% low (n = 920), and 58% no cardiovascular risk factors (n = 1670). The proportion of ubrogepant participants reporting a treatment-emergent adverse event was comparable across risk categories and similar to placebo. The treatment effects of ubrogepant versus placebo were consistent across cardiovascular risk categories for all efficacy outcomes. Conclusion: The safety and efficacy of ubrogepant for the acute treatment of a single migraine attack did not differ by the presence of major cardiovascular risk factors. No evidence of increased treatment-emergent adverse events or cardiac system organ class adverse events with ≥2 major cardiovascular risk factors and no safety concerns were identified. Trial Registration: ACHIEVE I ClinicalTrials.gov number, NCT02828020; ACHIEVE II ClinicalTrials.gov number, NCT02867709

Original languageEnglish (US)
Pages (from-to)979-990
Number of pages12
JournalCephalalgia
Volume41
Issue number9
DOIs
StatePublished - Aug 2021

Keywords

  • Calcitonin gene-related peptide
  • episodic migraine
  • gepant
  • pain freedom
  • vascular

ASJC Scopus subject areas

  • Clinical Neurology

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