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.