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 (ACHIEVE I: 50 mg, 34.4% [103/299], P = .0006 vs placebo; 100 mg, 34.3% [102/297], P = .0009 vs placebo; placebo, 22.0% [69/313]; ACHIEVE II: 25 mg, 34.1% [124/364], P < .0001 vs placebo; 50 mg, 33.4% [131/392], P = .0002 vs placebo; placebo, 20.7% [78/376]; pooled 50 mg, 33.9% [234/691], vs pooled placebo, 21.3% [147/689]; P < .0001).

Conclusions: A significantly higher proportion of participants treated with ubrogepant were able to function normally, were satisfied with the study medication, and reported clinically meaningful improvement compared with those receiving placebo. The results reinforce the potential benefits of ubrogepant on patient-centered outcomes in the acute treatment of migraine.

Keywords: calcitonin gene-related peptide; functional disability; headache; migraine; patient-reported outcomes; quality of life.

© 2020 The Authors. Headache: The Journal of Head and Face Pain published by Wiley Periodicals, Inc. on behalf of American Headache Society.

Figures

Figure 1

Participant disposition. aThe mITT population used for efficacy analyses included all randomized participants who received at least 1 dose of 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 hours after the initial dose. mITT = modified intention‐to‐treat. [Color figure can be viewed at https://wileyonlinelibrary.com]

Figure 2

Proportion of participants reporting ability to function normally on the Functional Disability Scale in (a) ACHIEVE I, (b) ACHIEVE II, and (c) the pooled analysis of ACHIEVE I and II. *P ≤ .01. P values are based on logistic regression with treatment group, baseline severity, historical triptan response, and use of medication for migraine prevention as factors and baseline value as a covariate. Missing values post baseline were imputed using the last observation carried forward approach. [Color figure can be viewed at https://wileyonlinelibrary.com]

Figure 3

Proportion of participants “satisfied” or “extremely satisfied” with study medication at 2 and 24 hours after initial dose in (a) ACHIEVE I, (b) ACHIEVE II, and (c) the pooled analysis of ACHIEVE I and II. *P < .002. P values are based on logistic regression with treatment group, baseline severity, historical triptan response, and use of medication for migraine prevention as factors. [Color figure can be viewed at https://wileyonlinelibrary.com]

Figure 4

Proportion of participants reporting that their migraine was “much better” or “very much better” on the Patient Global Impression of Change scale at 2 hours after initial dose in (a) ACHIEVE I, (b) ACHIEVE II, and (c) the pooled analysis of ACHIEVE I and II. *P ≤ .0009. P values are based on logistic regression, with treatment group, baseline severity, historical triptan response, and use of medication for migraine prevention as factors. [Color figure can be viewed at https://wileyonlinelibrary.com]