Conflict of Interest: Drs. Cady, Diener, and Mathew were principal investigators for this study and consulted in its design. Dr. Cady has received research support from and served on an advisory board for Johnson & Johnson Pharmaceutical Research & Development, L.L.C., and has also received fees from other companies. Dr. Diener has contributed to advisory boards and made oral presentations for Johnson & Johnson Pharmaceutical Research & Development, and has also received fees from other pharmaceutical companies. Dr. Mathew has received fees from other pharmaceutical companies. Drs. Haas, Hu, and Novak are employed by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Evaluation of Carisbamate for the Treatment of Migraine in a Randomized, Double-Blind Trial
Version of Record online: 3 FEB 2009
© 2009 the Authors. Journal compilation © 2009 American Headache Society
Headache: The Journal of Head and Face Pain
Volume 49, Issue 2, pages 216–226, February 2009
How to Cite
Cady, R. K., Mathew, N., Diener, H.-C., Hu, P., Haas, M. and Novak, G. P. (2009), Evaluation of Carisbamate for the Treatment of Migraine in a Randomized, Double-Blind Trial. Headache: The Journal of Head and Face Pain, 49: 216–226. doi: 10.1111/j.1526-4610.2008.01326.x
This study is registered at ClinicalTrials.gov corresponding to NCT number: 00109083.
- Issue online: 3 FEB 2009
- Version of Record online: 3 FEB 2009
- Accepted for publication October 26, 2008.
- antiepileptic drug
Objective.— This study explored the dose-response relationship of carisbamate administered at doses of 100 mg per day, 300 mg per day, or 600 mg per day, in the prevention of migraine.
Background.— Carisbamate ([S]-2-O-carbamoyl-1-o-chlorophenyl-ethanol; RWJ 333369) is a new chemical entity being studied for efficacy as adjunctive therapy in partial onset epilepsy. Because some antiepileptic drugs are also efficacious in migraine, for example, topiramate and valproate sodium, we tested carisbamate in migraine prophylaxis.
Design/Methods.— This was a double-blind, placebo-controlled trial, approximately 22-week duration. The primary efficacy variable was the percent reduction from baseline through the double-blind phase in average monthly migraine frequency using a 48-hour rule. Patients were randomized 1 : 1 : 1 : 1 to treatment with carisbamate 100, 300, or 600 mg per day, or placebo. Migraine attacks were counted during a prospective 4-week baseline period, which was followed by a 2-week titration period, a 12-week maintenance period, a 1-week medication reduction period, and a 3-week observation period. Patients had an established history of migraine, with or without aura, for at least 1 year and a 3-month history of 3-12 migraine attacks per month.
Results.— Patients (n = 323) were predominantly women (85%) and white (89%); mean age was 41 years. There were no statistically significant differences between any of the carisbamate groups and placebo (P ≥ .6) for the median (range) percentage reduction from baseline to end point in average monthly migraine frequency (P value vs placebo): 37% (−250%, 100%) for placebo; 33% (−210%, 100%; P = .7) CRS 100 mg/day; 27% (−100%, 100%; P = .8) CRS 300 mg/day; and 35% (−87%, 100%; P = .6) CRS 600 mg/day. Results for secondary efficacy measures (responder rate, percent reduction in average monthly migraine frequency using the 24-hour rule, and percent reduction in average monthly migraine days) were consistent (P ≥ .075). The proportion of patients discontinuing because of adverse events was similar for placebo and carisbamate-treated patients (13% each). The most common (occurring in ≥5% of patients) treatment-emergent adverse events in patients treated with carisbamate were fatigue (17%) and nasopharyngitis (13%). Fatigue appeared to be dose related.
Conclusions.— Carisbamate was not more efficacious in migraine prophylaxis than placebo in this well-controlled study that included a suitable population. However, carisbamate monotherapy was well tolerated at doses up to 600 mg per day.