Randomized, double-blind, placebo-controlled, parallel-group, multi-center study of the safety and efficacy of ADAM zolmitriptan for the acute treatment of migraine

Abstract

Objective: To determine the efficacy, tolerability, and safety of ascending doses of Adhesive Dermally-Applied Microarray (ADAM) zolmitriptan versus placebo for acute migraine treatment. Background: ADAM is a novel patient-administered system for intracutaneous drug administration. In a phase 1 pharmacokinetic study, zolmitriptan administered using ADAM had much faster absorption than oral administration with higher exposure in the first two hours. Methods: This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group Phase 2b/3 study evaluating ADAM zolmitriptan 1 mg, 1.9 mg, and 3.8 mg versus placebo. Co-primary endpoints were pain freedom and freedom from most bothersome other migraine-associated symptom 2 hours post-dose. Results: Of patients treated with ADAM zolmitriptan 3.8 mg or placebo, 41.5% and 14.2%, respectively were pain-free 2 hours post-dose (p = 0.0001) and 68.3% and 42.9% were free from their most bothersome other symptom (p = 0.0009). Due to the fixed sequential testing methodology, formal statistical significance was not established for secondary endpoints. However, the proportion of patients who were photophobia-free, phonophobia-free, and nausea-free at 2 hours post-dose was higher in the ADAM zolmitriptan 3.8 mg group compared with placebo, as were the percentages of patients who were pain-free, and who experienced pain relief up to 48 hours post-dose. Systemic adverse events were consistent with previous triptan trials, and included dizziness, paresthesia, muscle tightness, and nausea, all of which occurred in < 5% of patients in any group. Application site reactions were generally mild and resolved within 48 hours, although erythema and bruising persisted for longer periods in some patients. Conclusion: ADAM zolmitriptan 3.8 mg provides effective relief of migraine headache and associated most bothersome symptoms compared with placebo, and is well-tolerated. ClinicalTrials.gov: NCT02745392.