Randomized, controlled trial of telcagepant for the acute treatment of migraine

Abstract

Background: The neuropeptide calcitonin gene-related peptide (CGRP) plays a key role in migraine pathophysiology. In this large phase 3 clinical trial, we sought to confirm the efficacy of telcagepant, the first orally bioavailable CGRP receptor antagonist.

Methods: Adults with migraine with or without aura (International Headache Society criteria) treated a moderate or severe attack with oral telcagepant 50 mg (n = 177), 150 mg (n = 381), 300 mg (n = 371), or placebo (n = 365) in a randomized, double-blind trial. The 5 co-primary endpoints were pain freedom, pain relief, and absence of photophobia, absence of phonophobia, and absence of nausea, all at 2 hours postdose. The key secondary endpoint was 2-24 hour sustained pain freedom. The prespecified primary efficacy analyses evaluated the 150 mg and 300 mg groups; the 50-mg group was included on an exploratory basis to further characterize the dose response but was not prespecified for analysis. Tolerability was assessed by adverse experience reports.

Results: Telcagepant 300 mg was more effective (p <or= 0.001) than placebo on all primary endpoints and the key secondary endpoint, as was telcagepant 150 mg (p <or= 0.05). Telcagepant 300 mg showed a slight numeric advantage over telcagepant 150 mg on most measures. Telcagepant 50 mg values were numerically intermediate between placebo and telcagepant 150 mg and 300 mg. The percentages of patients with adverse experiences were 32.2% for telcagepant 50 mg, 32.0% for telcagepant 150 mg, 36.2% for telcagepant 300 mg, and 32.2% for placebo.

Conclusions: This study confirmed previous findings that telcagepant 300 mg was effective at relieving pain and other migraine symptoms at 2 hours and providing sustained pain freedom up to 24 hours. In this study, telcagepant 150 mg was also effective. Telcagepant was generally well tolerated.

Figures

Figure Trial profile *Patients had the option of taking a blinded second dose of study drug if the headache was still moderate or severe at 2 hours or for headache recurrence within 48 hours. †One fewer than the number initially treated because a patient randomized to telcagepant 300 mg took her sister’s medication instead (the sister was also in the study and was assigned to placebo). ‡One more than the number initially treated because of the patient randomized to telcagepant 300 mg who took placebo.