Objective: To summarize safety and tolerability data on orally administered almotriptan from premarketing clinical trials.
Background: Almotriptan is a new 5-HT1B/1D receptor agonist similar to sumatriptan in mode of action and therapeutic efficacy. In addition, the safety and tolerability profile of almotriptan has been demonstrated in a number of controlled clinical trials. Sumatriptan is generally safe and well tolerated; however, in controlled clinical trials, it has been associated with chest symptoms (pressure, warmth, and other unpleasant sensations) with an incidence of 3% to 5%.
Design: Three phase 1 dose-finding and pharmacokinetic studies in healthy men and women volunteers were reviewed to assess the safety and tolerability of oral almotriptan at single doses ranging from 2 to 200 mg. The objective of one study was to evaluate cardiovascular safety. Two phase 2 trials assessed the safety and tolerability of single doses of 2 to 150 mg in migraine (n=911). Two phase 3 trials assessed the safety and tolerability of a single 12.5-mg oral dose after three attacks (n=910) and repeated doses of 12.5 mg for multiple attacks over the long term (n=747). All studies were conducted in Europe. Data from the United States is currently being analyzed and will be published at a later date.
Results: In phase 2 and 3 trials comprising more than 2500 patients with migraine and 15 000 attacks, adverse events were infrequent and mild. The most common events-dizziness, nausea and vomiting, headache, fatigue, paresthesia, and drowsiness-were reported in fewer than 3% of patients. At the recommended therapeutic dose of 12.5 mg, the adverse events profile was not statistically different from placebo. The incidence of chest symptoms was 0.2% in the phase 3 trials. The long-term safety and tolerability profile after treatment of more than 10 000 attacks was similar to that following the single-dose studies. In all clinical trials, almotriptan demonstrated a very favorable adverse event profile, particularly with respect to nonischemic-related chest symptoms.
Conclusions: Almotriptan was safe and well tolerated in nearly all adult patients with migraine, with and without aura, enrolled in these studies. The incidence of chest symptoms in preclinical studies was substantially lower than that reported for sumatriptan in premarketing studies, indicating that almotriptan may be better tolerated than sumatriptan at clinically anticipated doses. However, any potential difference in cardiovascular safety between almotriptan and sumatriptan cannot be determined or inferred from this data. Cardiovascular risk profiles for all drugs within this class (triptans) should be considered similar. Only extensive postmarketing data, not currently available, can potentially change this recommendation.