MAP0004, orally inhaled DHE: a randomized, controlled study in the acute treatment of migraine.

OBJECTIVE To evaluate the efficacy and tolerability of MAP0004 compared with placebo for a single migraine in adult migraineurs: The FREEDOM-301 Study. BACKGROUND Acute treatment of migraine remains a clinical challenge despite the availability of triptans and other agents. Injectable dihydroergotamine, although effective, is considered invasive and inconvenient, and intranasal dihydroergotamine is associated with inconsistent systemic dosage delivery. MAP0004 is an orally inhaled formulation of dihydroergotamine delivered to the systemic circulation. In a phase 2 study, MAP0004 provided significant early onset of pain relief (10 minutes, P < .05) and sustained pain relief for up to 48 hours with a favorable adverse event profile. METHODS A phase 3, randomized, double-blind, placebo-controlled, parallel-group, single-attack, outpatient study of MAP0004, an inhaled dihydroergotamine was conducted at 102 sites in 903 adults with a history of episodic migraine. Patients were randomized (1:1) to receive MAP0004 (0.63 mg emitted dose; 1.0 mg nominal dose) or placebo, administered after onset of a migraine headache with moderate to severe pain. The co-primary endpoints were patient-assessed pain relief and absence of photophobia, phonophobia, and nausea at 2 hours after treatment. RESULTS A total of 903 patients (450 active, 453 placebo) were randomized, and 792 (395 active, 397 placebo) experienced a qualifying migraine. MAP0004 was superior to placebo in all 4 co-primary endpoints: pain relief (58.7% vs 34.5%, P < .0001), phonophobia free (52.9% vs 33.8%, P < .0001), photophobia free (46.6% vs 27.2%, P < .0001), and nausea free (67.1% vs 58.7%, P = .0210). Additionally, significantly more patients were pain-free at 2 hours following treatment with MAP0004 than with placebo (28.4% vs 10.1%, P < .0001). MAP0004 was well tolerated; no drug-related serious adverse events occurred. CONCLUSIONS In this study, MAP0004 was effective and well tolerated for the acute treatment of migraine with or without aura, providing statistically significant pain relief and freedom from photophobia, phonophobia, and nausea in adults with migraine compared with placebo.