A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy, Tolerability, and Safety of Celecoxib Oral Solution (ELYXYB) in Acute Treatment of Episodic Migraine with or without Aura

Abstract

Richard B Lipton,1 Sagar Munjal,2 Stewart J Tepper,3 Charlie Iaconangelo,4 Daniel Serrano4 1The Saul R. Korey Department of Neurology, Department of Psychiatry and Behavioral Sciences, Department of Epidemiology & Population Health, Albert Einstein College of Medicine and Montefiore Headache Center, New York, NY, USA; 2Operations & Medical Affairs Proprietary Products, Dr. Reddy’s Laboratories Inc., Princeton, NJ, USA; 3Geisel School of Medicine, Dartmouth College, Lebanon, NH, USA; 4Pharmerit - An Open Health Company, Bethesda, MD, USACorrespondence: Sagar Munjal Email [email protected]: Safe, effective, oral therapies are needed for acute treatment of migraine. This clinical trial assessed the efficacy, tolerability, and safety of celecoxib oral solution (ELYXYB) in a single migraine attack associated with moderate-to-severe pain.Methods: This was a phase III, randomized (1:1), double-blind, placebo-controlled trial, conducted at 41 US centers from December 2016 to October 2017. Adults with episodic migraine (with or without aura) for ≥ 1 year were treated with a single 4.8 mL dose of 120-mg celecoxib oral solution or placebo. Co-primary endpoints were the proportion of patients who were pain-free and free from the most bothersome migraine symptom (MBS) at 2 hours post-dose. The MBS was identified at screening from among nausea, photophobia, or phonophobia.Results: Six hundred thirty-one patients were randomized (celecoxib oral solution, n=316; placebo, n=315; mean age 41 years, range 18– 75; 84.3% female). One study site met prespecified outlier criteria (defined as a treatment effect estimate that was at least twice as large as all other sites) and was excluded from efficacy analyses. This site had a mean 2-hour pain freedom placebo response rate of 75% vs a combined mean of 23.5% for all other sites. In subsequent analysis, 2-hour post-dose pain freedom response rates were significantly higher in the celecoxib oral solution group vs placebo (32.8%, [27.2%, 38.8%]) vs 23.5%, [18.5%, 29.2%]; P=0.020). For 2-hour post-dose MBS freedom, response rates were significantly higher in the celecoxib oral solution group vs placebo (58.1% [51.4%, 64.5%] vs 43.9% [37.2%, 50.7%]; P=0.003). A total of 10.7% (31/289) of patients treated with celecoxib oral solution and 9.9% (28/283) of placebo-treated patients reported a treatment-emergent adverse event (TEAE). Study drug-related TEAEs were reported by 7.3% (21/289) and 7.4% (21/283) of celecoxib oral solution and placebo patients, respectively; the most common were nausea (celecoxib oral solution: 1.4% [4/289] vs placebo: 1.8% [5/283]) and dysgeusia (celecoxib oral solution: 1.7% [5/289] vs placebo: 1.1% [3/283]). No serious TEAEs, deaths, or drug-related TEAEs leading to withdrawal were reported.Conclusion: Celecoxib oral solution is a safe, effective COX-2-selective nonsteroidal anti-inflammatory drug for the treatment of acute migraine. In this analysis, celecoxib oral solution was significantly more effective than placebo and was also associated with a low rate of gastric TEAEs. Celecoxib oral solution may provide a convenient, alternate option to currently available treatments.Trial Registration: ClinicalTrials.gov Identifier: NCT03009019; registered January 4, 2017; retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03009019.Keywords: cyclooxygenase 2 inhibitors, migraine disorders, non-steroidal anti-inflammatory agents, clinical trial, phase III

Keywords

• cyclooxygenase 2 inhibitors
• migraine disorders
• non-steroidal anti-inflammatory agents
• clinical trial
• phase iii