PDF: ACHIEVE I & II
(2020)Objective
Ubrogepant – To evaluate patient-reported outcomes (functional disability, satisfaction, global impression of change) for the acute treatment of migraine in two phase 3 trials.
Study Summary
• Higher satisfaction rates with study medication at 2 and 24 hours versus placebo.
• Participants reported greater global improvement in migraine with ubrogepant.
• Benefits were consistent across ACHIEVE I and II; pooled analysis confirmed efficacy.
• Adverse event rates were similar between ubrogepant and placebo groups.
Intervention
Two phase 3, randomized, double-blind, placebo-controlled, single-attack trials (ACHIEVE I and II) evaluating oral ubrogepant (25, 50, or 100 mg) in adults with episodic migraine. Participants self-treated a qualifying moderate/severe migraine attack. Primary assessments included Functional Disability Scale (FDS), satisfaction at 2/24 hours, and Patient Global Impression of Change (PGIC).
Inclusion Criteria
Adults aged 18–75 with a ≥1-year history of migraine (with/without aura), 2–8 moderate/severe attacks per month, and no chronic migraine at enrollment. Preventive treatment allowed if attack frequency was below threshold.
Study Design
Arms: ACHIEVE I: Ubrogepant 50 mg, 100 mg, Placebo ACHIEVE II: Ubrogepant 25 mg, 50 mg, Placebo
Patients per Arm: ACHIEVE I: Placebo: 456, Ubrogepant 50 mg: 423, 100 mg: 448 ACHIEVE II: Placebo: 456, Ubrogepant 25 mg: 435, 50 mg: 464
Outcome
• Satisfaction at 24h: Ubrogepant 50 mg – 61.6% (ACHIEVE I), 60.8% (ACHIEVE II) vs Placebo ~35–39%; P < .0001.
• PGIC 'much/very much better' at 2h: Ubrogepant 50 mg – 33.9% pooled vs Placebo – 21.3%; OR ~1.9, P < .0001.
• Pooled analysis confirmed superior outcomes across all endpoints.
• Safety: Adverse events comparable to placebo; no major safety concerns.
Bottom Line
In two phase 3 trials, ubrogepant was significantly more effective than placebo in improving patient-reported ability to function normally, satisfaction with treatment, and overall impression of change for the acute treatment of a migraine attack.
Major Points
- This paper reports on patient-reported outcomes (PROs) from two pivotal, single-attack, phase 3 trials (ACHIEVE I and II) of ubrogepant, an oral calcitonin gene-related peptide (CGRP) receptor antagonist.
- Compared with placebo, a significantly greater proportion of participants treated with any dose of ubrogepant (25 mg, 50 mg, or 100 mg) reported being able to function normally at 2 hours post-dose.
- For the pooled 50 mg dose, 40.6% of participants achieved normal function at 2 hours, compared to 32.0% in the pooled placebo group (P < .0001).
- Patient satisfaction at 2 hours was significantly higher in all ubrogepant groups versus placebo; for the pooled 50 mg dose, 37.1% were 'satisfied' or 'extremely satisfied' compared to 24.5% for placebo (P < .0001).
- On the Patient Global Impression of Change (PGIC) scale, significantly more patients in the ubrogepant groups reported their migraine as 'much better' or 'very much better' at 2 hours compared to placebo.
- The incidence of adverse events was similar across all ubrogepant and placebo groups in both trials.
Study Design
- Study Type
- Multicenter, randomized, double-blind, placebo-controlled, parallel-group, single-attack, phase 3 trials
- Randomization
- Yes
- Blinding
- Double-blind (participants and investigators)
- Sample Size
- 3358
- Follow-up
- Assessments were conducted at 1, 2, 4, 8, and 24 hours after the initial dose.
- Centers
- 188
- Countries
- United States
Primary Outcome
Definition: The co-primary endpoints of the trials were 1) headache pain freedom at 2 hours post-dose and 2) absence of the most bothersome migraine-associated symptom at 2 hours post-dose. This paper focused on other patient-reported outcomes.
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| Pain freedom: 11.8-14.3%; Absence of most bothersome symptom: 27.4-27.8% | Ubrogepant 50mg: Pain freedom: 19.2-21.8%; Absence of most bothersome symptom: 38.6-38.9% | - | P≤.01 for both endpoints |
Limitations & Criticisms
- The trial design required participants to treat only moderate-to-severe attacks, so efficacy data for mild migraine attacks are not available.
- The follow-up for the Functional Disability Scale (FDS) was limited to 8 hours after the initial dose.
- Longer-term assessments (beyond 24 hours) and real-world data are needed to better understand the full impact of ubrogepant on functional disability and quality of life.
Citation
Headache 2020 60:686-700