Abstract
Objective: To compare the efficacy and tolerability of M207 1, 1.9, and 3.8mg to placebo for the acute treatment of migraine.
Background: Zosano Pharma has developed a new zolmitriptan intracutaneous system (M207). In a previous pharmacokinetic study, mean Tmax was approximately 15 minutes.
Design/Methods: This was a randomized, double-blind, placebo-controlled, dose-ranging trial in adults with migraine (+/− aura). Subjects selected their most bothersome headache-associated symptom (MBS: photophobia, phonophobia, or nausea) and entered a 28-day run-in period. Those who reported 2–8 migraine headaches during this period were randomized. Following randomization, they treated a qualifying migraine headache and recorded migraine symptoms and application site appearance for 48hr. Hierarchical statistical testing was utilized, starting with the co-primary endpoints (2-hour pain-free and 2-hour MBS-free) for the 3.8mg group. If a comparison was not significant, subsequent results were not considered statistically significant (p-values with asterisks are for descriptive purposes).
Results: 321 subjects treated and had at least one efficacy assessment (mITT). Demographics were similar among the groups. Pain-freedom at 2hr (p-value vs placebo) were 41.5% for 3.8 mg (p=0.0001), 27.7% for 1.9mg (p=0.0351), 30.4% for 1mg (p=0.0149*), and 14.3% for placebo. For MBS-free at 2hr, the percentages of subjects were 68.3% for 3.8mg (p=0.0009), 53.0% for 1.9mg (p=0.1694*), 57.0% for 1mg (p=0.0706*), and 42.9% for placebo. For sustained pain freedom 2–24hr and 2–48hr post-dose, the percentages of responders for 3.8mg were 31.7% versus 10.4% for placebo (p=0.0010*) and 26.8% versus 9.1% for placebo (p=0.0035*), respectively. Pain freedom at 1 hour favored 3.8mg (26.8%) versus placebo (10.4%) (p=0.0084*). M207 was well tolerated. The most common adverse events were mild application site reactions, primarily redness and bruising (6.3%–26.5%). The most common systemic adverse event was dizziness (4.8% of the 3.8mg subjects).
Conclusions: In this study, M207 3.8 mg was well-tolerated and effective at relieving pain and associated MBS of migraine.
Disclosure: Dr. Spierings has received research support from Teva Pharmaceuticals. Dr. Kellerman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Zosano Pharma. Dr. Schmidt has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Zosano Pharma.
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