Ubrogepant Is Safe and Efficacious in Participants Taking Concomitant Preventive Medication for Migraine: A Pooled Analysis of Phase 3 Trials

Abstract

Introduction: Ubrogepant is a calcitonin gene-related peptide receptor antagonist indicated for acute treatment of migraine that can be used to treat breakthrough attacks in individuals taking preventive treatment for migraine. We evaluated the impact of preventive medication use on the efficacy and safety of ubrogepant for the acute treatment of migraine.

Methods: This was an analysis of pooled efficacy data from the ACHIEVE I and ACHIEVE II phase 3 trials, in which efficacy of ubrogepant was assessed at 2 h after taking study medication for pain freedom, absence of most bothersome symptom (MBS), and pain relief. In addition, a long-term safety (LTS) extension trial was completed where safety was assessed on the basis of incidence and severity of treatment-emergent adverse events (TEAEs). Outcomes were compared between participants with or without prior (within 6 months) preventive medication use (anticonvulsants, beta blockers, antidepressants, or onabotulinumtoxinA). For efficacy analyses, data were pooled across ACHIEVE trials for the 50 mg and placebo groups; for safety analyses, data for all dose groups (50 mg and 100 mg) in the LTS trial were pooled.

Results: Preventive treatments were used by 417 of 2247 (18.6%) participants analyzed in the ACHIEVE trials and by 143 of 813 (17.5%) participants in the LTS trial. Responder rates for all outcomes were similar between participants with or without preventive treatment within each dose group (p > 0.05). No significant differences were noted across the different preventive medications. Rates and types of TEAEs were similar between participants with or without preventive treatment. No serious treatment-related adverse events were reported.

Conclusion: Efficacy and safety of ubrogepant for the acute treatment of migraine were similar between participants with or without prior or current use of concomitant preventive medication.

Trial registration: ClinicalTrials.gov identifiers: NCT02828020 (ACHIEVE I), NCT02867709 (ACHIEVE II), and NCT02873221 (long-term safety trial).

Keywords: Acute treatment; Concomitant therapies; Migraine; Preventive treatment; Ubrogepant.

© 2021. The Author(s).

Figures

Fig. 1

Trial schemas. F/U, follow-up; mITT, modified intent-to-treat [–21]

Fig. 2

Pain freedom response rates at 2 h after ubrogepant administration between participants with and without preventive treatment. The percentage of participants achieving pain freedom at 2 h after ubrogepant administration is shown for participants receiving placebo in both ACHIEVE I and ACHIEVE II (POOLED data; dark gray bars) or in ACHIEVE I only (light gray bars), for participants receiving ubrogepant 50 mg in both ACHIEVE I and ACHIEVE II (POOLED data; dark green bars), or ubrogepant 100 mg in ACHIEVE I only (light green bars) for participants who were taking preventive medication (left bars) or not (right bars). p values are based on Fisher exact test, two-tailed, vs placebo

Fig. 3

Absence of MBS response rates at 2 h after ubrogepant administration between participants with and without preventive treatment. The percentage of participants achieving absence of MBS at 2 h after ubrogepant administration is shown for participants receiving placebo in both ACHIEVE I and ACHIEVE II (POOLED data; dark gray bars) or in ACHIEVE I only (light gray bars), for participants receiving ubrogepant 50 mg in both ACHIEVE I and ACHIEVE II (POOLED data; dark green bars), or ubrogepant 100 mg in ACHIEVE I only (light green bars) for participants who were taking preventive medication (left bars) or not (right bars). p values are based on Fisher exact test, two-tailed, vs placebo. MBS, most bothersome symptom

Fig. 4

Pain relief response rates at 2 h after ubrogepant administration between participants with and without preventive treatment. The percentage of participants achieving pain freedom at 2 h after ubrogepant administration is shown for participants receiving placebo in both ACHIEVE I and ACHIEVE II (POOLED data; dark gray bars) or in ACHIEVE I only (light gray bars), for participants receiving ubrogepant 50 mg in both ACHIEVE I and ACHIEVE II (POOLED data; dark green bars), or ubrogepant 100 mg in ACHIEVE I only (light green bars) for participants who were taking preventive medication (left bars) or not (right bars). p values are based on Fisher exact test, two-tailed, vs placebo