ACHIEVE I & II
(2020)Objective
Ubrogepant – To evaluate patient-reported outcomes (functional disability, satisfaction with study medication, and global impression of change) for the acute treatment of migraine in two phase 3 trials.
Study Summary
• Satisfaction rates at 2 and 24 hours were significantly higher with ubrogepant than placebo.
• Participants reported greater 'much/very much better' PGIC scores with ubrogepant at 2 hours.
• Findings were replicated across ACHIEVE I and II; a post hoc pooled 50 mg analysis reinforced the effect.
• These PRO endpoints were prespecified but not primary or secondary endpoints of the parent trials (co-primary endpoints were pain freedom and absence of the most bothersome symptom at 2 hours).
• Treatment-emergent adverse-event rates were similar between ubrogepant and placebo.
Intervention
Two phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group, single-attack trials (ACHIEVE I, 89 US sites; ACHIEVE II, 99 US sites) evaluating oral ubrogepant (25, 50, or 100 mg) in adults with episodic migraine. Participants self-treated a qualifying moderate/severe migraine attack, taking study medication no later than 4 hours after headache onset. An optional second dose of study medication or rescue medication (acetaminophen, NSAID, opioid, antiemetic, triptan) was permitted 2–48 hours after the initial dose. The parent-trial co-primary endpoints were headache pain freedom and absence of the most bothersome migraine-associated symptom at 2 hours post-dose. The patient-reported outcomes reported in this article — Functional Disability Scale (FDS), satisfaction with study medication at 2 and 24 hours, and Patient Global Impression of Change (PGIC) at 2 hours — were prespecified additional analyses and were not primary or secondary endpoints.
Inclusion Criteria
Adults aged 18–75 with a ≥1-year history of migraine (with or without aura) diagnosed per ICHD-3 (beta) criteria, and 2–8 migraine attacks with moderate to severe headache pain in each of the 3 months before screening. Current chronic migraine was excluded; participants with a previous diagnosis of chronic migraine were eligible only if they were currently experiencing fewer than 15 headache days per month while taking concomitant preventive treatment.
Study Design
Arms: ACHIEVE I: Ubrogepant 50 mg, 100 mg, Placebo ACHIEVE II: Ubrogepant 25 mg, 50 mg, Placebo
Patients per Arm: ACHIEVE I (randomized): Placebo 559, Ubrogepant 50 mg 556, 100 mg 557 (mITT: 456 / 423 / 448) ACHIEVE II (randomized): Placebo 563, Ubrogepant 25 mg 561, 50 mg 562 (mITT: 456 / 435 / 464) Pooled 50 mg vs pooled placebo (mITT): 887 vs 912
Outcome
• Satisfaction/extremely satisfied at 24h: ACHIEVE I – 50 mg 61.6% [233/378], 100 mg 59.0% [230/390] vs Placebo 35.3% [140/397] (P < .0001). ACHIEVE II – 25 mg 55.1% [217/411], 50 mg 60.8% [253/416] vs Placebo 39.4% [162/411] (P < .0001). Pooled 50 mg 61.2% [486/794] vs pooled Placebo 37.4% [302/808], P < .0001.
• PGIC 'much better'/'very much better' at 2h: ACHIEVE I – 50 mg 34.4% [103/299] (P = .0006), 100 mg 34.3% [102/297] (P = .0009) vs Placebo 22.0% [69/313]. ACHIEVE II – 25 mg 34.1% [124/364] (P < .0001), 50 mg 33.4% [131/392] (P = .0002) vs Placebo 20.7% [78/376]. Pooled 50 mg 33.9% [234/691] vs pooled Placebo 21.3% [147/689]; OR 1.88 (95% CI 1.47, 2.39), P < .0001.
• Safety: Incidence of treatment-emergent adverse events was similar between ubrogepant and placebo groups in each trial.