TY - JOUR
T1 - Randomized controlled trial of the CGRP receptor antagonist MK-3207 in the acute treatment of migraine
AU - Hewitt, David J.
AU - Aurora, Sheena K.
AU - Dodick, David W.
AU - Goadsby, Peter J.
AU - Ge, Yang
AU - Bachman, Robert
AU - Taraborelli, Donna
AU - Fan, Xiaoyin
AU - Assaid, Christopher
AU - Lines, Christopher
AU - Ho, Tony W.
N1 - Funding Information:
This study was funded by Merck & Co., Inc. The authors would like to thank Sheila Erespe from Merck for assistance in formatting the manuscript and Scott Grossman for helpful comments on a draft version.
Funding Information:
S.K.A. has received grant and research support from Advanced Bionics, Alexza, Allergan, GlaxoSmithKline, MAP Pharmaceuticals, Merck, Ortho-McNeil, Neuralieve and Takeda; has served as a consultant for Ortho-McNeil Pharmaceutical, Merck, GlaxoSmithKline, Allergan and Neuralieve; and has received honoraria from Merck, GlaxoSmithKline, NuPathe and Ortho-McNeil Pharmaceutical.
PY - 2011/4
Y1 - 2011/4
N2 - Background: This study evaluated the CGRP receptor antagonist MK-3207 for acute treatment of migraine. Methods: Multicenter, double-blind, randomized, placebo-controlled, parallel-group, two-stage adaptive study with two interim efficacy analyses to facilitate optimal dose selection. Migraine patients were initially randomized to MK-3207 2.5, 5, 10, 20, 50 and 100 mg or placebo to treat a moderate/severe migraine. One or more doses were to be discontinued based on the first interim analysis and a lower or higher dose could be added based on the second interim analysis. The primary endpoint was two-hour pain freedom. Results: A total of 547 patients took study medication. After the first interim analysis, the two lowest MK-3207 doses (2.5, 5 mg) were identified as showing insufficient efficacy. Per the pre-specified adaptive design decision rule, only the 2.5-mg group was discontinued and the five highest doses (5, 10, 20, 50, 100 mg) were continued into the second stage. After the second interim efficacy analysis, a 200 mg dose was added due to insufficient efficacy at the top three (20, 50, 100 mg) doses. A positive dose-response trend was demonstrated when data were combined across all MK-3207 doses for two-hour pain freedom (p < .001). The pairwise difference versus placebo for two-hour pain freedom was significant for 200 mg (p < .001) and nominally significant for 100 mg and 10 mg (p < .05). The incidence of adverse events appeared comparable between active treatment groups and placebo, and did not appear to increase with increasing dose. Conclusions: MK-3207 was effective and generally well tolerated in the acute treatment of migraine.
AB - Background: This study evaluated the CGRP receptor antagonist MK-3207 for acute treatment of migraine. Methods: Multicenter, double-blind, randomized, placebo-controlled, parallel-group, two-stage adaptive study with two interim efficacy analyses to facilitate optimal dose selection. Migraine patients were initially randomized to MK-3207 2.5, 5, 10, 20, 50 and 100 mg or placebo to treat a moderate/severe migraine. One or more doses were to be discontinued based on the first interim analysis and a lower or higher dose could be added based on the second interim analysis. The primary endpoint was two-hour pain freedom. Results: A total of 547 patients took study medication. After the first interim analysis, the two lowest MK-3207 doses (2.5, 5 mg) were identified as showing insufficient efficacy. Per the pre-specified adaptive design decision rule, only the 2.5-mg group was discontinued and the five highest doses (5, 10, 20, 50, 100 mg) were continued into the second stage. After the second interim efficacy analysis, a 200 mg dose was added due to insufficient efficacy at the top three (20, 50, 100 mg) doses. A positive dose-response trend was demonstrated when data were combined across all MK-3207 doses for two-hour pain freedom (p < .001). The pairwise difference versus placebo for two-hour pain freedom was significant for 200 mg (p < .001) and nominally significant for 100 mg and 10 mg (p < .05). The incidence of adverse events appeared comparable between active treatment groups and placebo, and did not appear to increase with increasing dose. Conclusions: MK-3207 was effective and generally well tolerated in the acute treatment of migraine.
KW - CGRP
KW - MK-3207
KW - migraine
KW - randomized trial
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U2 - 10.1177/0333102411398399
DO - 10.1177/0333102411398399
M3 - Article
C2 - 21383045
AN - SCOPUS:79954607744
SN - 0333-1024
VL - 31
SP - 712
EP - 722
JO - Cephalalgia
JF - Cephalalgia
IS - 6
ER -