Assessment of the Consistency of Absorption of Dihydroergotamine Following Oral Inhalation: Pooled Results from Four Clinical Studies

Background: MAP0004 is an investigational orally inhaled dihydroergotamine (DHE) delivered via a TEMPO (R) metered dose inhaler that was effective in the acute treatment of migraine in a large Phase 3 trial. Rapid and consistent absorption of DHE is important for efficacy in the acute treatment of migraine. Methods: The pharmacokinetic parameters from four recent clinical studies, with doses including the proposed clinical dose of 1.0mg nominal (0.65mg emitted) MAP0004, were assessed for the consistency and speed of absorption of DHE. Results: Across these studies, MAP0004 administration resulted in rapid DHE absorption, with a median time of maximum concentration (C-max) of approximately 10min. The C-max and area under the curve from time zero to 2hr associated with the MAP0004 1.0mg nominal dose were also similar between the three studies with this dose. C-max values after 1.0mg MAP0004 administration were consistently lower than for 1.0mg intravenous DHE administration, and C-max appeared to correlate with incidence of nausea. In these studies, DHE absorption through the lung was fast, consistent, and not associated with any unique tolerability issues for this route of administration. Conclusions: These results provide evidence of the consistency of absorption that can be achieved with the use of an appropriate metered dose inhaler, which may translate into a predictable therapeutic response.