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

Abstract

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.

• Authors: David J Hewitt, Sheena K Aurora, David W Dodick, Peter J Goadsby, Yang Joy Ge, Robert Bachman, Donna Taraborelli, Xiaoyin Fan, Christopher Assaid, Christopher Lines, Tony W Ho
• Journal: Cephalalgia : an international journal of headache (Cephalalgia) Vol. 31 Issue 6 Pg. 712-22 (Apr 2011) ISSN: 1468-2982 [Electronic] England
• PMID: 21383045 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• 2-(8-(3,5-difluorophenyl)-10-oxo-6,9-diazaspiro(4.5)dec-9-yl)-N-(2'-oxo-1,1',2',3-tetrahydrospiro(indene-2,3'-pyrrolo(2,3-b)pyridin)-5-yl)acetamide
• Bridged Bicyclo Compounds, Heterocyclic
• Calcitonin Gene-Related Peptide Receptor Antagonists
• Spiro Compounds

Topics

• Acute Disease
• Adult
• Bridged Bicyclo Compounds, Heterocyclic (administration & dosage, adverse effects)
• Calcitonin Gene-Related Peptide Receptor Antagonists
• Dose-Response Relationship, Drug
• Female
• Humans
• Male
• Middle Aged
• Migraine Disorders (drug therapy)
• Placebo Effect
• Severity of Illness Index
• Spiro Compounds (administration & dosage, adverse effects)
• Treatment Outcome