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.