OBJECTIVE: To evaluate whether the calcitonin gene-related peptide (CGRP) 
receptor antagonist telcagepant might be effective for migraine prevention.
METHODS: In this randomized, double-blind, placebo-controlled, multicenter trial 
(ClinicalTrials.gov NCT00797667), patients experiencing 3-14 migraine days 
during a 4-week baseline were randomized to telcagepant 140 mg, telcagepant 280 
mg, or placebo twice daily for 12 weeks. Efficacy was assessed by mean monthly 
headache days and migraine/probable migraine days (headache plus ≥ 1 associated 
symptom).
RESULTS: The trial was terminated following a recommendation from the Safety 
Monitoring Board due to hepatotoxicity concerns. At termination, the planned 660 
patients had been randomized, 656 had been treated with ≥ 1 dose of study 
medication, and 14 had completed the trial. The mean treatment duration was 
48-50 days. Thirteen patients, all in the telcagepant groups, had an alanine 
aminotransferase (ALT) elevation ≥ 3 × the upper limit of normal and 7 of these 
also had an aspartate aminotransferase elevation ≥ 3 × the upper limit of 
normal. Two patients had very high symptomatic transaminase elevations that 
occurred within 2-6 weeks of treatment initiation and resolved after treatment 
discontinuation. The originally planned efficacy analysis over 12 weeks was not 
performed due to limited data at later time points, but there was evidence that 
telcagepant resulted in a larger reduction from baseline than placebo for mean 
monthly headache days (month 1: 140 mg = -2.9, 280 mg = -3.1, placebo = -1.7; p 
< 0.05) and migraine/probable migraine days (month 1: 140 mg = -2.7, 280 mg = 
-3.0, placebo = -1.6; p < 0.05).
CONCLUSIONS: These data suggest a potential role for CGRP receptor antagonism in 
migraine prophylaxis. However, the observed aminotransferase elevations do not 
support the use of telcagepant for daily administration.
CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in 
patients with migraine, telcagepant taken daily reduces headache days by 1.4 
days per month compared to placebo and causes 2.5% of patients to have 
elevations of serum ALT levels.