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

Cephalalgia. 2011 Apr;31(6):712-22. doi: 10.1177/0333102411398399. Epub 2011 Mar 7.


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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Bridged Bicyclo Compounds, Heterocyclic / administration & dosage*
  • Bridged Bicyclo Compounds, Heterocyclic / 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*
  • Spiro Compounds / adverse effects
  • Treatment Outcome


  • 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