Randomized controlled trial of an oral CGRP receptor antagonist, MK-0974, in acute treatment of migraine

Neurology. 2008 Apr 15;70(16):1304-12. doi: 10.1212/01.WNL.0000286940.29755.61. Epub 2007 Oct 3.


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.

Trial registration: ClinicalTrials.gov NCT00246337.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Azepines / administration & dosage*
  • Azepines / therapeutic use
  • Calcitonin Gene-Related Peptide Receptor Antagonists*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Humans
  • Imidazoles / administration & dosage*
  • Imidazoles / therapeutic use
  • Male
  • Migraine Disorders / drug therapy*
  • Migraine Disorders / metabolism*
  • Migraine Disorders / physiopathology
  • Receptors, Calcitonin Gene-Related Peptide / physiology
  • Time Factors


  • Azepines
  • Calcitonin Gene-Related Peptide Receptor Antagonists
  • Imidazoles
  • Receptors, Calcitonin Gene-Related Peptide
  • telcagepant

Associated data

  • ClinicalTrials.gov/NCT00246337