High-dose zolmitriptan nasal spray was not found to be associated with complete pain relief at 2 hours among pediatric patients with migraine headache; however, some improvement in migraine symptoms was reported by the study participants. These findings from a phase 3, randomized, double-blind, placebo-controlled, crossover trial were published in Headache.
Patients (N=300) aged 6 to 11 years who experienced at least 2 monthly attacks of migraine without aura lasting at least 3 hours were recruited at 48 centers in the United States between 2017 and 2020. During a run-in period, the patients were to receive treatment with 1 dose of placebo approximately 20 minutes after the headache pain reached moderate or severe intensity. The patients who did not respond to treatment with placebo (n=168) were then randomly assigned to receive 1 of 2 sequences of placebo or zolmitriptan nasal spray crossover treatments to treat 1 migraine attack during a 6-week period. Patients in the zolmitriptan nasal spray cohort who weighed less than 50 kg were further assigned in a 5:1 ratio to receive zolmitriptan nasal spray 2.5 mg or zolmitriptan nasal spray 1 mg, and those weighting 50 kg or greater were assigned in a 5:1 ratio to receive zolmitriptan nasal spray 5 mg or zolmitriptan nasal spray 2.5 mg. The primary efficacy endpoint was the proportion of patients who were pain-free 2 hours after the administration of treatment. The state of being pain-free was defined as a pain score of 0 without rescue medication or sleep.
The mean age of patients in the run-in portion of the trial was 9.0 (standard deviation [SD], 1.5) years, 58.00% were White, the average age of onset of migraine attacks was 6.3 (SD, 2.0) years, and patients experienced an average of 5.1 (SD, 2.6) migraines each month.
Compared with placebo, high-dose zolmitriptan nasal spray was not found to be associated with pain-free status 2 hours postdose (odds ratio [OR], 1.51; 95% CI, 0.96-2.38; P =.0777).
High-dose zolmitriptan nasal spray improved the secondary endpoints of pain-free status 1 hour postdose (OR, 2.14; P =.0459), headache response 1 hour postdose (OR, 2.09; P =.0040), no phonophobia 2 hours postdose (OR, 1.92; P =.0017), headache response 30 minutes postdose (OR, 1.88; P =.0274), sustained headache response at 2 to 24 hours (OR, 1.84; P =.0056), no photophobia 2 hours postdose (OR, 1.82; P =.0088), headache response 2 hours postdose (OR, 1.75; P =.0090), sustained pain-free response at 2 to 24 hours (OR, 1.66; P =.0375), no phonophobia 1 hour postdose (OR, 1.55; P =.0273), and no photophobia 1 hour postdose (OR, 1.54; P =.0373) compared with placebo.
A total of 135 patients chose to enter a 6-month open-label extension period during which time 11.1% of patients were reported to be pain free 2 hours following treatment with zolmitriptan nasal spray.
Treatment-emergent adverse events reported by recipients of zolmitriptan nasal spray in the double-blind period of the study included abdominal pain (n=1), a burning sensation (n=1), syncope (n=1), and throat irritation (n=1). During the extension period, 15 treatment-emergent adverse events reported, of which influenza, diarrhea, nausea, vomiting, viral pharyngitis, and somnolence were the most common.
A major limitation of this study was that it was underpowered to detect significant differences in the primary endpoint.
The authors of this study found that zolmitriptan nasal spray did not meet the primary endpoint of achieving pain-free status 2 hours postdose among pediatric patients with migraine without aura; however, multiple secondary pain endpoints were met. The study authors concluded, “Photophobia, phonophobia, nausea, and vomiting are an integral part of migraine as per ICHD criteria. Thus, despite the fact that the primary endpoint was not achieved, ZNS treatment may provide clinically relevant benefit in this younger population.”
Disclosure: This study was funded by AstraZeneca. All study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Yonker ME, McVige J, Zeitlin L, Visser H. 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. Headache. 2022;62(9):1207-1217. doi:10.1111/head.14391