Disclosure: This study was funded by Merck Research Laboratories. The funding organization was involved in the following: design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, and approval of the manuscript. All authors are responsible for the work described in this paper. All authors were involved in at least one of the following: (conception, design, acquisition, analysis, statistical analysis, interpretation of data) and (drafting the manuscript and/or revising the manuscript for important intellectual content). All authors provided final approval of the version to be published.
Randomized Controlled Study of Telcagepant Plus Ibuprofen or Acetaminophen in Migraine
Article first published online: 1 APR 2011
© 2011 American Headache Society
Headache: The Journal of Head and Face Pain
Volume 51, Issue 4, pages 533–543, April 2011
How to Cite
Hewitt, D. J., Martin, V., Lipton, R. B., Brandes, J., Ceesay, P., Gottwald, R., Schaefer, E., Lines, C. and Ho, T. W. (2011), Randomized Controlled Study of Telcagepant Plus Ibuprofen or Acetaminophen in Migraine. Headache: The Journal of Head and Face Pain, 51: 533–543. doi: 10.1111/j.1526-4610.2011.01860.x
Conflict of Interest: David J. Hewitt, Paulette Ceesay, Regina Gottwald, Eleanor Schaefer, Christopher Lines, and Tony W. Ho are employees of Merck and own stock/stock options in Merck. Vincent Martin has served as a consultant for Merck, Allergan, Nautilus, and MAP Pharmaceuticals; he has received grants from Merck, Endo, and GSK, and has also served as a speaker for Nautilus and GSK. Richard Lipton has received clinical research grants and has acted as a consultant for Merck; he has consulted for or undertaken research funded by other manufacturers of drugs and devices for migraine. Jan Brandes received grants, research, and educational support or served as a consultant to Merck, GlaxoSmithKline, UCB Pharma, Pfizer, Allergan, Johnson and Johnson, AstraZeneca, Bristol-Myers Squibb, Winston Laboratories, Sanofi-Aventis, Elan Pharmaceuticals, Forest Laboratories, Novartis, Endo, Pozen, Vernalis, Ortho McNeil, Advanced Bionics, MedPointe Pharmaceuticals, and Aradigm Corporation.
- Issue published online: 1 APR 2011
- Article first published online: 1 APR 2011
- Accepted for publication January 17, 2011.
- calcitonin gene-related peptide;
- nonsteroidal anti-inflammatory drug;
Objective.— To evaluate the efficacy and tolerability of telcagepant when co-administered with ibuprofen or acetaminophen for the acute treatment of migraine.
Background.— Telcagepant is an oral calcitonin gene-related peptide receptor antagonist which is being evaluated for the acute treatment of migraine. Combining telcagepant with analgesics that have a different mechanism of action could produce greater efficacy.
Methods.— Randomized, double-blind, placebo-controlled study. Patients were randomized to treat a moderate or severe migraine headache with either telcagepant 280 mg + ibuprofen 400 mg (N = 171), telcagepant 280 mg + acetaminophen 1000 mg (N = 171), telcagepant 280 mg (N = 170), or placebo (N = 171). The primary efficacy endpoint was 2-hour pain freedom. The study had approximately 88% power to detect an additive effect of at least 15 percentage points (telcagepant combination vs telcagepant monotherapy) and 48% power to detect an additive effect of at least 10 percentage points. Safety and tolerability were assessed by adverse events and laboratory tests.
Results.— The percentages of patients with 2-hour pain freedom were greater in each active treatment group compared to placebo (P < .001): telcagepant + ibuprofen = 35.2%, telcagepant + acetaminophen = 38.3%, telcagepant = 31.2%, placebo = 10.9%. No significant differences were seen for either of the combination groups vs telcagepant monotherapy, but both were numerically larger than telcagepant monotherapy. All the active treatments were generally well tolerated. The percentage of patients reporting any adverse event within 48 hours was higher in the active treatment groups than placebo: telcagepant + ibuprofen = 30.3%, telcagepant + acetaminophen = 31.6%, telcagepant = 24.8%, placebo = 18.2%. The most common adverse events reported by ≥4 patients in one or more of the treatment groups that included telcagepant were fatigue, nausea, dizziness, somnolence, dry mouth, and tremor.
Conclusions.— The combination of telcagepant 280 mg with either ibuprofen 400 mg or acetaminophen 1000 mg did not show a statistically significant difference from telcagepant alone. Numerically greater treatment effects in the combination treatment groups over the telcagepant 280 mg monotherapy suggest that telcagepant combination treatments may merit further evaluation in studies powered to detect smaller additive benefits. (Clinicaltrials.gov; NCT00758836).