BACKGROUND: Calcitonin gene-related peptide (CGRP) probably has a role in 
migraine pathophysiology, and antagonism of its receptors might provide 
treatment without the vasoconstrictor effects of triptans. We aimed to assess 
the clinical profile of MK-0974 (telcagepant), an orally bioavailable antagonist 
of CGRP receptor.
METHODS: In a randomised, parallel-treatment, placebo-controlled, double-blind, 
trial at 81 sites in the Europe and the USA, adults with migraine diagnosed by 
International Headache Society criteria treated moderate or severe attacks with 
either oral telcagepant 150 mg or 300 mg, zolmitriptan 5 mg, or placebo. The 
five co-primary endpoints were pain freedom, pain relief, or absence of 
photophobia, phonophobia, or nausea at 2 h after treatment. Analysis was by the 
full analysis set and multiplicity was controlled for with a step-down 
closed-testing procedure. This trial is registered with ClinicalTrials.gov, 
number NCT00442936.
FINDINGS: 1380 patients were randomly assigned to receive telcagepant 150 mg 
(n=333) or 300 mg (354), zolmitriptan (345), or placebo (348). Telcagepant 300 
mg was more effective than placebo for pain freedom (95 [27%] of 353 patients vs 
33 [10%] of 343 [p<0.0001]), pain relief (194 [55%] of 353 vs 95 [28%] of 343 
[p<0.0001]), and absences of phonophobia (204 [58%] of 353 vs 126 [37%] of 342 
[p<0.0001]), photophobia (180 [51%] of 353 vs 99 [29%] of 342 [p<0.0001]), and 
nausea (229 [65%] of 352 vs 189 [55%] of 342 [p=0.0061]). Efficacy of 
telcagepant 300 mg and zolmitriptan 5 mg were much the same, and both were more 
effective than telcagepant 150 mg. Adverse events were recorded for 31% taking 
telcagepant 150 mg, 37% taking telcagepant 300 mg, 51% taking zolmitriptan 5 mg, 
and 32% taking placebo.
INTERPRETATION: Telcagepant 300 mg is effective as an acute treatment for 
migraine with efficacy comparable to that of zolmitriptan 5 mg, but with fewer 
associated adverse effects.
FUNDING: Merck Research Laboratories.