Randomized controlled trial of the CGRP receptor antagonist MK-3207 in the acute treatment of migraine

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 (Joy)

AU - Bachman, Robert

AU - Taraborelli, Donna

AU - Fan, Xiaoyin

AU - Assaid, Christopher

AU - Lines, Christopher

AU - Ho, Tony W.

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

KW - 5-HT1B/1D AGONISTS

KW - TRIPTANS

KW - TELCAGEPANT

KW - HEADACHE

KW - BLOCKADE

U2 - 10.1177/0333102411398399

DO - 10.1177/0333102411398399

M3 - Article

SN - 0333-1024

VL - 31

SP - 712

EP - 722

JO - Cephalalgia

JF - Cephalalgia

IS - 6

ER -