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From Merck Research Laboratories (T.W.H., X.F., C.A., C.F., C.J.J., C.R.L.), North Wales, PA; Headache Associates/ClinExcel Research (L.K.M.), Cincinnati, OH; and The New England Center for Headache (A.M.R.), Stamford, CT.
Address correspondence and reprint requests to Dr. Tony Ho, Merck Research Laboratories, UG 4C-18, PO Box 1000, North Wales, PA 19454-1099 tony_ho{at}merck.com.
Objective: To determine an effective and tolerable dose of a novel oral calcitonin gene-related peptide (CGRP) receptor antagonist, MK-0974, for the acute treatment of migraine.
Methods: Randomized, double-blind, parallel-group, clinical trial with a two-stage, adaptive, dose-ranging design. Patients were allocated to treat a moderate or severe migraine attack with MK-0974 (25, 50, 100, 200, 300, 400, or 600 mg), rizatriptan 10 mg, or placebo taken orally. The primary endpoint was pain relief (reduction to mild or none) 2 hours after dosing. Secondary endpoints included pain freedom at 2 hours and sustained pain relief at 24 hours. A prespecified, blinded, automated interim analysis was used to discontinue randomization to less effective doses.
Results: Per the adaptive study design, the four lowest MK-0974 groups (25, 50, 100, 200 mg) were discontinued due to insufficient efficacy. For the remaining treatment groups, the estimated pain relief proportions at 2 hours were 300 mg (n = 38) 68.1%, 400 mg (n = 45) 48.2%, 600 mg (n = 40) 67.5%, rizatriptan 10 mg (n = 34) 69.5%, and placebo (n = 115) 46.3%. The prespecified primary efficacy hypothesis test, which compared the average 2-hour pain relief response proportion of the combined 300, 400, and 600 mg MK-0974 groups to placebo, was significant (P = 0.015). A generally similar efficacy pattern was seen for other endpoints. MK-0974 was generally well tolerated and there did not appear to be an increase in adverse events with increasing dose.
Conclusions: The novel, orally administered calcitonin gene-related peptide (CGRP) receptor antagonist, MK-0974, was effective and generally well tolerated for the acute treatment of migraine.
Abbreviations: APT = all patients treated; CGRP = calcitonin gene-related peptide; NSAID = nonsteroidal anti-inflammatory drug.
e-Pub ahead of print on October 3, 2007, at www.neurology.org.
*Participating investigators are listed in the appendix.
Disclosure: This study was funded by Merck Research Laboratories. Dr. Mannix has received grants in excess of $10,000 for research activities not reported in this article and received honoraria in excess of $10,000 from Merck during the course of this study. Dr. Rapoport received honoraria in excess of $10,000 from Merck during the course of this study. Drs. Ho, Fan, Assaid, and Lines, C. Furtek, and C.J. Jones are employees of Merck. Drs. Ho, Fan, Assaid, and Lines have an equity interest in excess of $10,000 in Merck. Merck employees were involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, and approval of the manuscript.
Received March 30, 2007. Accepted in final form June 25, 2007.
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