Tolerability and consistency of effect of Zolmitriptan nasal spray in a long-term migraine treatment trial

To primarily assess the tolerability of zolmitriptan (Zomig) nasal spray 5mg in the long-term treatment of migraine, as well as determine efficacy and consistency of effect over time (up to 1 year). This randomised, double-blind-to-dose, parallel-group, multicentre study was designed as a two-phase, crossover trial with a total duration of 1 year. In the pre-crossover phase, 1,093 patients aged 18-65 years with an established diagnosis of migraine with or without aura received intranasal zolmitriptan 5, 2.5, 1 or 0.5mg for the treatment of mild, moderate or severe migraine attacks. When a headache persisted or recurred, a second dose of zolmitriptan nasal spray (or other approved escape medication) was permitted 2 hours post-administration but no later than 24 hours after the first dose. In the post-crossover phase, once a placebo-controlled, dose-finding study had established 5mg as the dose with the optimal clinical utility, all patients were crossed over under blinded conditions to receive this dose. As this was primarily a safety study, the primary endpoints for the study were the incidence and nature of all serious adverse events (at any time before or after administration) and nonserious adverse events (within 24 hours of administration), as well as the incidence of clinically significant abnormalities in either ECG or haematology and clinical chemistry parameters. Nose and throat examinations were performed before and after the study at 30 predetermined trial centres. Other endpoint measures included headache response rate, pain-free assessments, reduction in headache intensity, time to resumption of normal activities and consistency of headache response. Efficacy rates were measured in 90-day intervals up to a period of 360 days. Zolmitriptan nasal spray 5mg was well tolerated, with only 1.9% of patients withdrawing from the 12-month long-term trial because of adverse events. Adverse events occurred in 22.1% of attacks treated with zolmitriptan nasal spray 5mg, and the majority were of short duration and mild or moderate intensity. Serious adverse events occurred in 0.2% of attacks treated with zolmitriptan nasal spray 5mg. There was no evidence of increased incidence of adverse events with increasing duration of treatment. Nasopharyngeal adverse events were reported in 5.5% of attacks treated with zolmitriptan nasal spray 5mg. Again, events were generally transient and of mild intensity. For the 1,093 patients who treated 13,806 attacks during the