Ubrogepant, an Acute Treatment for Migraine, Improved Patient‐Reported Functional Disability and Satisfaction in 2 Single‐Attack Phase 3 Randomized Trials, ACHIEVE I and II

Abstract

Objective To evaluate the efficacy of ubrogepant on patient‐reported functional disability, satisfaction with study medication, and global impression of change. Background Ubrogepant is a small‐molecule, oral calcitonin gene‐related peptide receptor antagonist indicated for the acute treatment of migraine. In 2 phase 3 trials (ACHIEVE I and II), ubrogepant demonstrated efficacy vs placebo on the 2 co‐primary endpoints of headache pain freedom and absence of the most bothersome migraine‐associated symptom at 2 hours post dose for the 50 and 100 mg doses. Patient‐reported outcomes, such as functional disability, satisfaction, and patient global impression of change, can provide additional evidence of the efficacy of an acute treatment for migraine on clinically meaningful and patient‐relevant outcomes. Methods ACHIEVE I and ACHIEVE II were multicenter, randomized, double‐blind, placebo‐controlled, parallel‐group, single‐attack trials in adults (18‐75 years) with migraine. In ACHIEVE I, participants were randomized 1:1:1 to placebo or ubrogepant 50 or 100 mg; in ACHIEVE II, participants were randomized 1:1:1 to placebo or ubrogepant 25 or 50 mg to treat a migraine attack with moderate or severe headache pain. Participants rated ability to perform daily activities on the Functional Disability Scale, before dosing and at 1, 2, 4, and 8 hours after the initial dose; satisfaction with study medication at 2 and 24 hours; and impression of overall change in migraine on the Patient Global Impression of Change scale at 2 hours. In prespecified analyses for each trial, each outcome was compared between each ubrogepant dose group and the relevant placebo group. Data were pooled from the ubrogepant 50 mg and placebo groups of the 2 trials in a post hoc analysis. Results In ACHIEVE I, 559 participants were randomized to placebo, 556 to ubrogepant 50 mg, and 557 to ubrogepant 100 mg; in ACHIEVE II, 563 were randomized to placebo, 561 to ubrogepant 25 mg, and 562 to ubrogepant 50 mg. At 2 hours post dose, significantly higher proportions of ubrogepant‐treated participants vs placebo‐treated participants reported being able to function normally (ACHIEVE I: ubrogepant 50 mg, 40.6% [171/421], P = .0012 vs placebo; ubrogepant 100 mg, 42.9% [192/448], P < .0001 vs placebo; placebo, 29.8% [136/456]; ACHIEVE II: ubrogepant 25 mg, 42.6% [185/434], P = .0015 vs placebo; ubrogepant 50 mg, 40.5% [188/464], P = .0118 vs placebo; placebo, 34.2% [156/456]; pooled 50 mg, 40.6% [359/885], vs pooled placebo, 32.0% [292/912]; P < .0001), were satisfied/extremely satisfied with study medication (ACHIEVE I: 50 mg, 36.3% [147/405], P < .0001 vs placebo; 100 mg, 35.8% [149/416], P = .0002 vs placebo; placebo, 24.1% [104/432]; ACHIEVE II: 25 mg, 35.1% [141/402], P = .0018 vs placebo; 50 mg, 37.8% [163/431], P < .0001 vs placebo; placebo, 24.8% [106/427]; pooled ubrogepant 50 mg, 37.1% [310/836], vs pooled placebo, 24.5% [210/859]; P < .0001), and indicated that their migraine was much/very much better on the Patient Global Impression of Change scale (A...

Remote Electrical Neuromodulation for the Acute Treatment of Migraine in Patients with Chronic Migraine: An Open-Label Pilot Study

“…Improvement in function at 2 h was also consistent across attacks, with almost half of the patients achieving this outcome. Approximately 30% of patients returned to normal function at 2 h in most of their attacks, similar to results reported for lasmiditan, ubrogepant, and rimegepant, although these were reported for a single attack in people without chronic migraine [4,40,41].…”

Multiple imputation score tests and an application to Cochran‐Mantel‐Haenszel statistics

“…We consider the primary time point to be two hours after the initial dose, and we use the last‐observation‐carried‐forward approach as the primary method for imputing missing data after the initial dose. As reported by Dodick et al, 11 significantly higher proportions of ubrogepant‐treated participants reported being able to function normally at two hours after the initial dose relative to placebo‐treated participants. Here, we analyze the FDS data as an ordinal response variable and use the multiple imputation method to handle missing data.…”

The American Headache Society Position Statement On Integrating New Migraine Treatments Into Clinical Practice

“…Emerging agents with novel mechanisms of action that have demonstrated efficacy for the acute treatment of migraine include the small molecule CGRP receptor antagonists, ubrogepant [69][70][71][72] and rimegepant, [73][74][75][76] and lasmiditan, 77 a selective serotonin (5-HT 1F ) receptor agonist. Unlike triptans and ergotamine derivatives, these novel treatment options do not result in constriction of blood vessels and may have a special role in patients with cardiovascular contraindications to triptans.…”