A randomized, double blind, placebo-controlled study of MAP0004 in adult patients with migraine.

Background: Dihydroergotamine mesylate (DHE) is an effective treatment for acute migraine, but its effective use is often limited by the inconvenience and inconsistency of intranasal, intramuscular, or subcutaneous routes of administration. A new formulation of DHE delivered through the lungs by the novel Tempo inhaler is being developed and is designed to offer fast onset, consistent dosing, and sustained response.

Objective: This proof of principle and dose setting study evaluated the efficacy and tolerability of inhaled DHE delivered by a breath-synchronized, plume-controlled inhaler (Tempo) in adult migraineurs.

Methods: This was a randomized, double blind, placebo-controlled, 2-period study conducted at 9 headache centers in the United States. Adult men and women with a documented history of acute migraine for at least 12 months, with an average of 2 to 8 attacks per month in the preceding 6 months were treated with MAP0004 0.5 or 1.0 mg systemic equivalent dose (1.0 or 2.0 mg nominal dose) or matching placebo during Treatment Period 1 (TP1). Patients who responded to treatment during TP1 were re-randomized in Treatment Period 2 (TP2) to receive MAP0004 0.25 mg systemic equivalent dose or placebo.

Results: Of 86 patients randomized to treatment, 69 were included in the As-Treated population in TP1. Pain relief at 2 hours was greater for MAP0004 0.5 mg (72%, P = .019) and 1.0 mg (65%, P = .071) than for placebo (33%). Pain relief at 10 (32%), 15 (46%), and 30 (55%) minutes was significantly (P < .05) greater with MAP0004 0.5 mg than with placebo (0%, 7% and 14%, respectively). Pain-free at 2 hours was significantly greater with MAP0004 0.5 mg (44%, P = .015) and 1.0 mg (35%, P = .050) than with placebo (7%). Total migraine relief at 2 hours was significantly (P = .019) greater with MAP0004 0.5 mg (72%) than with placebo (33%). Sustained pain relief and pain-free rates exhibited a therapeutic gain of 30% (P = .066) and 31% (P = .037) at 24 hours and 28% (P = .096) and 30% (P = .057) at 48 hours with MAP0004 0.5 mg vs placebo. MAP0004 was well tolerated with no serious or severe adverse events. Dysgeusia was reported as treatment-related in 2 patients on placebo, 0 patients on MAP0004 0.5 mg, and 6 patients on MAP0004 1.0 mg. No clinically relevant changes were noted in spirometry, vital signs, electrocardiogram, or clinical laboratory values. No significant differences between treatments were observed in TP2.

Conclusions: In this study MAP0004 0.5 mg and 1.0 mg were well tolerated and effective at delivering clinically significant, rapid, and sustained pain relief in adult migraine patients. No additional benefit was observed with the higher dose, thus the MAP0004 0.5 mg systemic equivalent dose has been selected as the dose for further clinical study.