Claims for Patent: 11,185,497

Summary for Patent: 11,185,497

Title:	Intranasal delivery of dihydroergotamine by precision olfactory device
Abstract:	Methods are provided for acutely treating migraine headache with or without aura. The methods comprise administering to a subject with migraine headache an effective dose of a liquid pharmaceutical composition comprising dihydroergotamine (DHE) or a salt thereof, wherein the dose is administered by an intranasal delivery device that provides, following intranasal administration, (a) a mean peak plasma DHE concentration (C.sub.max) of at least 750 pg/ml, (b) with a mean time to C.sub.max (T.sub.max) of DHE of less than 45 minutes, and (c) a mean plasma AUC.sub.0-inf of DHE of at least 2500 pg*hr/ml. Also provided are kits for acutely treating migraine with or without aura in which a liquid pharmaceutical composition comprising DHE or DHE salt is contained within a sealed vial that is attachable to a precision intranasal olfactory delivery device packaged therewith.
Inventor(s):	Hoekman; John D. (Seattle, WA), Satterly; Kelsey H. (Seattle, WA), Shrewsbury; Stephen B. (Fallbrook, CA), Youmans; Scott (Bothell, WA), Fuller; Christopher (Seattle, WA)
Assignee:	Impel Neuropharma, Inc. (Seattle, WA)
Application Number:	17/062,364
Patent Claims:	1. A method of acutely treating migraine headache with or without aura, comprising: administering, via a manually actuated, metered-dose, propellant-driven intranasal delivery device, to a subject with migraine headache an effective dose of a liquid pharmaceutical composition comprising 4 mg/mL of dihydroergotamine (DHE) mesylate, wherein the effective dose comprises 1.45 mg of DHE mesylate administered as two divided doses of one spray per each nostril without requiring a timed wait between the two divided doses, and wherein the manually actuated, metered-dose, propellant-driven intranasal delivery device is configured to sequentially release the liquid pharmaceutical composition followed by propellant, and wherein, following administration of the dose, the mean DHE C.sub.max in plasma is at least 750 pg/ml; the time to C.sub.max (T.sub.max) of DHE in plasma is less than 45 minutes; and the mean plasma AUC.sub.0-inf of DHE is at least 2500 pg*hr/ml. 2. The method of claim 1, wherein, following administration of the dose, the mean plasma AUC.sub.0-inf of DHE is at least 6000 pg*hr/ml. 3. The method of claim 1, wherein, prior to first manual actuation, the liquid pharmaceutical composition and propellant are not in contact within the device. 4. The method of claim 1, wherein each manual actuation brings a metered volume of liquid pharmaceutical composition and a separately metered volume of propellant into contact within a dose chamber of the device. 5. The method of claim 4, wherein contact of propellant with liquid pharmaceutical composition within the dose chamber of the device creates a spray of liquid pharmaceutical composition as the formulation is expelled through a nozzle of the device.