BOSTON—Telcagepant (formerly known as MK-0974), a calcitonin gene–related peptide (CGRP) receptor antagonist, significantly relieved migraine pain and migraine-associated symptoms two hours after dosing, according to results of a phase III study presented at the 50th Annual Scientific Meeting of the American Headache Society.
Efficacy results for telcagepant 300 mg were similar to those for zolmitriptan 5 mg with a lower incidence of adverse events, said Tony W. Ho, MD, Senior Director of Clinical Neuroscience at Merck Research Laboratories in North Wales, Pennsylvania.
The neuropeptide CGRP, believed to play a role in the pathophysiology of migraine, “is widely expressed in both the CNS and peripheral nervous system,” said Dr. Ho. “Telcagepant is a novel, orally available CGRP receptor antagonist in development with a new neuronal mechanism of action without direct vasoconstriction.”
A total of 1,380 patients 18 and older who had a single moderate or severe migraine attack (per International Headache Society criteria) were randomized to telcagepant 150 mg (n = 333), telcagepant 300 mg (n = 354), zolmitriptan 5 mg (n = 345), or placebo (n = 348). Patients were primarily women (85%; average age, 43), representing a typical acute migraine population, with no significant differences between the groups.
Five primary end points were assessed two hours after treatment: pain relief (reduction to mild or none) and freedom from pain, photophobia, phonophobia, and nausea. Secondary end points included sustained freedom from pain at two to 24 hours (without use of second study dose or rescue medication), total freedom from migraine (defined as pain freedom without any associated symptoms) at two hours postdose, and total freedom from migraine at two to 24 hours.
Telcagepant 300 mg was more effective than placebo on all primary end points. At two hours, 55% of patients who received telcagepant reported a reduction in pain, compared with 56% for zolmitriptan and 28% for placebo. “Two-thirds of the patients treated a moderate migraine attack, and one-third treated a severe migraine attack,” said Dr. Ho. “Approximately 18% of the patients treated a migraine with aura, and approximately 15% were on migraine prophylactic medications.”
Rates of two-hour freedom from pain and absence of phonophobia, photophobia, and nausea were 27%, 58%, 51%, and 65%, respectively, for the telcagepant 300-mg dose, compared with 31%, 55%, 50%, and 71%, respectively, for zolmitriptan and 10%, 37%, 29%, and 55%, respectively, for placebo.
Significant differences were also seen for telcagepant 150 mg versus placebo and zolmitriptan 5 mg versus placebo. Telcagepant 300 mg had comparable efficacy to zolmitriptan 5 mg; telcagepant 150 mg was slightly less effecitve than both telcagepant 300 mg and zolmitriptan 5 mg.
“Telcagepant was very well tolerated in this trial,” Dr. Ho said adding that typical triptan-like side effects were observed with zolmitriptan but not with telcagepant. Overall, nonserious adverse events occurred in 31.4% of the telcagepant 150-mg group, 37.2% of the telcagepant 300-mg group, 50.7% of the zolmitriptan 5-mg group, and 32.1% of the placebo group. The most common side effects among patients using telcagepant were dry mouth (6%), dizziness (5%), somnolence (5%), nausea (5%), and fatigue (5%). No serious adverse events were reported.
This study was not designed to show either the equivalence or noninferiority of telcagepant versus zolmitriptan.