Effect of ubrogepant vs placebo on pain and the most bothersome associated symptom in the acute treatment of migraine: The achieve ii randomized clinical trial

Richard B. Lipton, David W. Dodick, Jessica Ailani, Kaifeng Lu, Michelle Finnegan, Armin Szegedi, Joel M. Trugman

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Importance: Ubrogepant is an oral calcitonin gene-related peptide receptor antagonist under investigation for acute treatment of migraine. Objective: To evaluate the efficacy and tolerability of ubrogepant compared with placebo for acute treatment of a single migraine attack. Design, Setting, and Participants: Phase 3, multicenter, randomized, double-blind, placebo-controlled, single-attack, clinical trial (ACHIEVE II) conducted in the United States (99 primary care and research clinics; August 26, 2016-February 26, 2018). Participants were adults with migraine with or without aura experiencing 2 to 8 migraine attacks per month. Interventions: Ubrogepant 50 mg (n = 562), ubrogepant 25 mg (n = 561), or placebo (n = 563) for a migraine attack of moderate or severe pain intensity. Main Outcomes and Measures: Co-primary efficacy outcomes were pain freedom and absence of the participant-designated most bothersome migraine-associated symptom (among photophobia, phonophobia, and nausea) at 2 hours after taking the medication. Results: Among 1686 randomized participants, 1465 received study treatment (safety population; mean age, 41.5 years; 90% female); 1355 of 1465 (92.5%) were evaluable for efficacy. Pain freedom at 2 hours was reported by 101 of 464 participants (21.8%) in the ubrogepant 50-mg group, 90 of 435 (20.7%) in the ubrogepant 25-mg group, and 65 of 456 (14.3%) in the placebo group (absolute difference for 50 mg vs placebo, 7.5%; 95% CI, 2.6%-12.5%; P =.01; 25 mg vs placebo, 6.4%; 95% CI, 1.5%-11.5%; P =.03). Absence of the most bothersome associated symptom at 2 hours was reported by 180 of 463 participants (38.9%) in the ubrogepant 50-mg group, 148 of 434 (34.1%) in the ubrogepant 25-mg group, and 125 of 456 (27.4%) in the placebo group (absolute difference for 50 mg vs placebo, 11.5%; 95% CI, 5.4%-17.5%; P =.01; 25 mg vs placebo, 6.7%; 95% CI, 0.6%-12.7%; P =.07). The most common adverse events within 48 hours of any dose were nausea (50 mg, 10 of 488 [2.0%]; 25 mg, 12 of 478 [2.5%]; and placebo, 10 of 499 [2.0%]) and dizziness (50 mg, 7 of 488 [1.4%]; 25 mg, 10 of 478 [2.1%]; placebo, 8 of 499 [1.6%]). Conclusions and Relevance: Among adults with migraine, acute treatment with ubrogepant compared with placebo led to significantly greater rates of pain freedom at 2 hours with 50-mg and 25-mg doses, and absence of the most bothersome migraine-associated symptom at 2 hours only with the 50-mg dose. Further research is needed to assess the effectiveness of ubrogepant against other acute treatments for migraine and to evaluate the long-term safety of ubrogepant among unselected patient populations. Trial Registration: ClinicalTrials.gov Identifier: NCT02867709.

Original languageEnglish (US)
Pages (from-to)1887-1898
Number of pages12
JournalJAMA - Journal of the American Medical Association
Volume322
Issue number19
DOIs
StatePublished - Nov 19 2019

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Migraine Disorders
Randomized Controlled Trials
Placebos
Pain
Therapeutics
Nausea
Hyperacusis
Calcitonin Gene-Related Peptide Receptors
Migraine without Aura
Safety
Migraine with Aura
Photophobia
Dizziness
Research
Population
Primary Health Care
Outcome Assessment (Health Care)
Clinical Trials

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Effect of ubrogepant vs placebo on pain and the most bothersome associated symptom in the acute treatment of migraine : The achieve ii randomized clinical trial. / Lipton, Richard B.; Dodick, David W.; Ailani, Jessica; Lu, Kaifeng; Finnegan, Michelle; Szegedi, Armin; Trugman, Joel M.

In: JAMA - Journal of the American Medical Association, Vol. 322, No. 19, 19.11.2019, p. 1887-1898.

Research output: Contribution to journalArticle

Lipton, Richard B. ; Dodick, David W. ; Ailani, Jessica ; Lu, Kaifeng ; Finnegan, Michelle ; Szegedi, Armin ; Trugman, Joel M. / Effect of ubrogepant vs placebo on pain and the most bothersome associated symptom in the acute treatment of migraine : The achieve ii randomized clinical trial. In: JAMA - Journal of the American Medical Association. 2019 ; Vol. 322, No. 19. pp. 1887-1898.
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abstract = "Importance: Ubrogepant is an oral calcitonin gene-related peptide receptor antagonist under investigation for acute treatment of migraine. Objective: To evaluate the efficacy and tolerability of ubrogepant compared with placebo for acute treatment of a single migraine attack. Design, Setting, and Participants: Phase 3, multicenter, randomized, double-blind, placebo-controlled, single-attack, clinical trial (ACHIEVE II) conducted in the United States (99 primary care and research clinics; August 26, 2016-February 26, 2018). Participants were adults with migraine with or without aura experiencing 2 to 8 migraine attacks per month. Interventions: Ubrogepant 50 mg (n = 562), ubrogepant 25 mg (n = 561), or placebo (n = 563) for a migraine attack of moderate or severe pain intensity. Main Outcomes and Measures: Co-primary efficacy outcomes were pain freedom and absence of the participant-designated most bothersome migraine-associated symptom (among photophobia, phonophobia, and nausea) at 2 hours after taking the medication. Results: Among 1686 randomized participants, 1465 received study treatment (safety population; mean age, 41.5 years; 90{\%} female); 1355 of 1465 (92.5{\%}) were evaluable for efficacy. Pain freedom at 2 hours was reported by 101 of 464 participants (21.8{\%}) in the ubrogepant 50-mg group, 90 of 435 (20.7{\%}) in the ubrogepant 25-mg group, and 65 of 456 (14.3{\%}) in the placebo group (absolute difference for 50 mg vs placebo, 7.5{\%}; 95{\%} CI, 2.6{\%}-12.5{\%}; P =.01; 25 mg vs placebo, 6.4{\%}; 95{\%} CI, 1.5{\%}-11.5{\%}; P =.03). Absence of the most bothersome associated symptom at 2 hours was reported by 180 of 463 participants (38.9{\%}) in the ubrogepant 50-mg group, 148 of 434 (34.1{\%}) in the ubrogepant 25-mg group, and 125 of 456 (27.4{\%}) in the placebo group (absolute difference for 50 mg vs placebo, 11.5{\%}; 95{\%} CI, 5.4{\%}-17.5{\%}; P =.01; 25 mg vs placebo, 6.7{\%}; 95{\%} CI, 0.6{\%}-12.7{\%}; P =.07). The most common adverse events within 48 hours of any dose were nausea (50 mg, 10 of 488 [2.0{\%}]; 25 mg, 12 of 478 [2.5{\%}]; and placebo, 10 of 499 [2.0{\%}]) and dizziness (50 mg, 7 of 488 [1.4{\%}]; 25 mg, 10 of 478 [2.1{\%}]; placebo, 8 of 499 [1.6{\%}]). Conclusions and Relevance: Among adults with migraine, acute treatment with ubrogepant compared with placebo led to significantly greater rates of pain freedom at 2 hours with 50-mg and 25-mg doses, and absence of the most bothersome migraine-associated symptom at 2 hours only with the 50-mg dose. Further research is needed to assess the effectiveness of ubrogepant against other acute treatments for migraine and to evaluate the long-term safety of ubrogepant among unselected patient populations. Trial Registration: ClinicalTrials.gov Identifier: NCT02867709.",
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TY - JOUR

T1 - Effect of ubrogepant vs placebo on pain and the most bothersome associated symptom in the acute treatment of migraine

T2 - The achieve ii randomized clinical trial

AU - Lipton, Richard B.

AU - Dodick, David W.

AU - Ailani, Jessica

AU - Lu, Kaifeng

AU - Finnegan, Michelle

AU - Szegedi, Armin

AU - Trugman, Joel M.

PY - 2019/11/19

Y1 - 2019/11/19

N2 - Importance: Ubrogepant is an oral calcitonin gene-related peptide receptor antagonist under investigation for acute treatment of migraine. Objective: To evaluate the efficacy and tolerability of ubrogepant compared with placebo for acute treatment of a single migraine attack. Design, Setting, and Participants: Phase 3, multicenter, randomized, double-blind, placebo-controlled, single-attack, clinical trial (ACHIEVE II) conducted in the United States (99 primary care and research clinics; August 26, 2016-February 26, 2018). Participants were adults with migraine with or without aura experiencing 2 to 8 migraine attacks per month. Interventions: Ubrogepant 50 mg (n = 562), ubrogepant 25 mg (n = 561), or placebo (n = 563) for a migraine attack of moderate or severe pain intensity. Main Outcomes and Measures: Co-primary efficacy outcomes were pain freedom and absence of the participant-designated most bothersome migraine-associated symptom (among photophobia, phonophobia, and nausea) at 2 hours after taking the medication. Results: Among 1686 randomized participants, 1465 received study treatment (safety population; mean age, 41.5 years; 90% female); 1355 of 1465 (92.5%) were evaluable for efficacy. Pain freedom at 2 hours was reported by 101 of 464 participants (21.8%) in the ubrogepant 50-mg group, 90 of 435 (20.7%) in the ubrogepant 25-mg group, and 65 of 456 (14.3%) in the placebo group (absolute difference for 50 mg vs placebo, 7.5%; 95% CI, 2.6%-12.5%; P =.01; 25 mg vs placebo, 6.4%; 95% CI, 1.5%-11.5%; P =.03). Absence of the most bothersome associated symptom at 2 hours was reported by 180 of 463 participants (38.9%) in the ubrogepant 50-mg group, 148 of 434 (34.1%) in the ubrogepant 25-mg group, and 125 of 456 (27.4%) in the placebo group (absolute difference for 50 mg vs placebo, 11.5%; 95% CI, 5.4%-17.5%; P =.01; 25 mg vs placebo, 6.7%; 95% CI, 0.6%-12.7%; P =.07). The most common adverse events within 48 hours of any dose were nausea (50 mg, 10 of 488 [2.0%]; 25 mg, 12 of 478 [2.5%]; and placebo, 10 of 499 [2.0%]) and dizziness (50 mg, 7 of 488 [1.4%]; 25 mg, 10 of 478 [2.1%]; placebo, 8 of 499 [1.6%]). Conclusions and Relevance: Among adults with migraine, acute treatment with ubrogepant compared with placebo led to significantly greater rates of pain freedom at 2 hours with 50-mg and 25-mg doses, and absence of the most bothersome migraine-associated symptom at 2 hours only with the 50-mg dose. Further research is needed to assess the effectiveness of ubrogepant against other acute treatments for migraine and to evaluate the long-term safety of ubrogepant among unselected patient populations. Trial Registration: ClinicalTrials.gov Identifier: NCT02867709.

AB - Importance: Ubrogepant is an oral calcitonin gene-related peptide receptor antagonist under investigation for acute treatment of migraine. Objective: To evaluate the efficacy and tolerability of ubrogepant compared with placebo for acute treatment of a single migraine attack. Design, Setting, and Participants: Phase 3, multicenter, randomized, double-blind, placebo-controlled, single-attack, clinical trial (ACHIEVE II) conducted in the United States (99 primary care and research clinics; August 26, 2016-February 26, 2018). Participants were adults with migraine with or without aura experiencing 2 to 8 migraine attacks per month. Interventions: Ubrogepant 50 mg (n = 562), ubrogepant 25 mg (n = 561), or placebo (n = 563) for a migraine attack of moderate or severe pain intensity. Main Outcomes and Measures: Co-primary efficacy outcomes were pain freedom and absence of the participant-designated most bothersome migraine-associated symptom (among photophobia, phonophobia, and nausea) at 2 hours after taking the medication. Results: Among 1686 randomized participants, 1465 received study treatment (safety population; mean age, 41.5 years; 90% female); 1355 of 1465 (92.5%) were evaluable for efficacy. Pain freedom at 2 hours was reported by 101 of 464 participants (21.8%) in the ubrogepant 50-mg group, 90 of 435 (20.7%) in the ubrogepant 25-mg group, and 65 of 456 (14.3%) in the placebo group (absolute difference for 50 mg vs placebo, 7.5%; 95% CI, 2.6%-12.5%; P =.01; 25 mg vs placebo, 6.4%; 95% CI, 1.5%-11.5%; P =.03). Absence of the most bothersome associated symptom at 2 hours was reported by 180 of 463 participants (38.9%) in the ubrogepant 50-mg group, 148 of 434 (34.1%) in the ubrogepant 25-mg group, and 125 of 456 (27.4%) in the placebo group (absolute difference for 50 mg vs placebo, 11.5%; 95% CI, 5.4%-17.5%; P =.01; 25 mg vs placebo, 6.7%; 95% CI, 0.6%-12.7%; P =.07). The most common adverse events within 48 hours of any dose were nausea (50 mg, 10 of 488 [2.0%]; 25 mg, 12 of 478 [2.5%]; and placebo, 10 of 499 [2.0%]) and dizziness (50 mg, 7 of 488 [1.4%]; 25 mg, 10 of 478 [2.1%]; placebo, 8 of 499 [1.6%]). Conclusions and Relevance: Among adults with migraine, acute treatment with ubrogepant compared with placebo led to significantly greater rates of pain freedom at 2 hours with 50-mg and 25-mg doses, and absence of the most bothersome migraine-associated symptom at 2 hours only with the 50-mg dose. Further research is needed to assess the effectiveness of ubrogepant against other acute treatments for migraine and to evaluate the long-term safety of ubrogepant among unselected patient populations. Trial Registration: ClinicalTrials.gov Identifier: NCT02867709.

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