A multicenter, randomized, double-blind, placebo-controlled, crossover trial to evaluate the efficacy and safety of zolmitriptan nasal spray for the acute treatment of migraine in patients aged 6 to 11 years, with an open-label extension

Objective To evaluate the efficacy and safety of zolmitriptan nasal spray (ZNS) in the acute treatment of migraine headache in patients aged 6 to 11 years. Background Triptans have demonstrated efficacy in adults, but pediatric studies of these agents have largely failed and there are few triptan options for these patients. Because lack of response to 1 triptan does not necessarily preclude response to an alternate triptan, additional triptan options for pediatric patients are desirable. Methods This Phase 3, randomized, double-blind, placebo-controlled, multicenter crossover trial with an open-label extension enrolled patients aged 6 to 11 years with a diagnosis of migraine for >= 6 months and >= 16 headache-free days/month (N = 373). After a run-in period to eliminate placebo responders, 186 patients were randomized within their body weight stratum to ZNS followed by matching placebo, or placebo followed by matching ZNS. Patients <50 kg who were randomly allocated to ZNS were randomized to 5:1 to ZNS 2.5 or 1.0 mg; those >= 50 kg were randomized 5:1 to ZNS 5.0 or 2.5 mg. Patients had 6 weeks to treat 1 moderate to severe migraine headache and then crossed over to the alternate arm, during which they had 6 weeks to treat a second migraine attack. Patients could participate in a subsequent 6-month outpatient open-label extension. The primary efficacy endpoint was pain-free status at 2 h in patients treated with the high dose from each stratum. Results The trial was terminated early due to slow enrollment. Three hundred patients (mean age, 9 years) entered the placebo run-in period and 186 entered the double-blind period. Pain-free status at 2 h postdose was achieved by 45/133 (33.8%) and 30/128 (23.4%) of patients who received high-dose ZNS and placebo, respectively (p = 0.0777; odds ratio [OR] 1.51; 95% confidence interval [CI] 0.96, 2.38). Several secondary endpoints achieved statistical significance. There were few treatment-related adverse events and none led to discontinuation. ZNS retained efficacy and demonstrated a consistent safety profile throughout the 6-month open-label extension. Conclusion The effect of high-dose ZNS on the primary endpoint of pain-free status at 2 h did not achieve statistical significance. ZNS was safe and well tolerated in this pediatric population.

Automated summary

The study aimed to evaluate the efficacy and safety of ZNS nasal spray in the acute treatment of migraine in patients aged 6 to 11 years. The high-dose ZNS did not achieve statistical significance in pain-free status at 2 hours, but demonstrated good safety and tolerability in this pediatric population.