Intranasal DHE for the Treatment of Headache

Abstract

Presented herein are powder formulations comprising dihydroergotamine (DHE), or a pharmaceutically acceptable salt thereof. In addition to such formulations, also presented herein are methods comprising intranasally administering powder formulations comprising dihydroergotamine, or a pharmaceutically acceptable salt thereof. The presented methods can be used for treating headache, for example, for rapid onset treatment of headache, including migraine, e.g. acute treatment of migraine with or without aura.

What is claimed is: 
     
         1 . A pharmaceutical nasal dosage form, comprising: dihydroergotamine or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable excipient for treating migraine with or without aura in a human subject, wherein said pharmaceutical nasal dosage form is provided in a pre-primed nasal device. 
     
     
         2 . The pharmaceutical nasal dosage form of  claim 1 , wherein said pharmaceutical nasal dosage form requires less than about 15 minutes to administer an effective dose of dihydroergotamine. 
     
     
         3 . The pharmaceutical nasal dosage form of  claim 2 , wherein said pharmaceutical nasal dosage form requires a single spray or two sprays to administer said effective dose of dihydroergotamine. 
     
     
         4 . The pharmaceutical nasal dosage form of  claim 2 , wherein said effective dose of dihydroergotamine is from about 0.5 mg to about 2 mg. 
     
     
         5 . The pharmaceutical nasal dosage form of  claim 1 , wherein said dihydroergotamine or said pharmaceutically acceptable salt thereof is present from about 0.5 mg to about 10 mg. 
     
     
         6 . The pharmaceutical nasal dosage form of  claim 1 , wherein said dihydroergotamine or said pharmaceutically acceptable salt thereof is present from about 1.5 mg to about 6 mg. 
     
     
         7 . The pharmaceutical nasal dosage form of  claim 1 , wherein said pharmaceutical nasal dosage form comprises said pharmaceutically acceptable salt of dihydroergotamine that is dihydroergotamine mesylate. 
     
     
         8 . The pharmaceutical nasal dosage form of  claim 1 , wherein said pharmaceutically acceptable excipient comprises microcrystalline cellulose. 
     
     
         9 . The pharmaceutical nasal dosage form of  claim 8 , wherein said microcrystalline cellulose is present in an amount of about 15% to 99% of a total weight of said pharmaceutical nasal dosage form. 
     
     
         10 . The pharmaceutical nasal dosage form of  claim 8 , wherein said microcrystalline cellulose component has a mean particle size diameter of about 100 μm or less. 
     
     
         11 . The pharmaceutical nasal dosage form of  claim 8 , wherein said microcrystalline cellulose component has a mean particle size diameter of about 30 μm or less. 
     
     
         12 . A method comprising administering a pharmaceutical nasal dosage form of dihydroergotamine or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable excipient, wherein said pharmaceutical nasal dosage form is administered using a pre-primed nasal device and requires less than four sprays to administer an effective dose of dihydroergotamine for treating migraine with or without aura in a human subject. 
     
     
         13 . The method of  claim 12 , wherein said pharmaceutical nasal dosage form requires less than about 15 minutes for said administration. 
     
     
         14 . The method of  claim 12 , wherein said effective dose is from about 0.5 mg to about 2 mg of dihydroergotamine. 
     
     
         15 . The method of  claim 12 , wherein said effective dose is from about 1.5 mg to about 6 mg of dihydroergotamine. 
     
     
         16 . The method of  claim 12 , wherein said administration comprises two sprays. 
     
     
         17 . The method of  claim 12 , wherein said pharmaceutically acceptable excipient comprises microcrystalline cellulose. 
     
     
         18 . The method of  claim 12 , wherein said pharmaceutical nasal dosage form upon intranasal administration to a human subject provides at least about 10% higher AUC 0-t , AUC 0-inf , or AUC 0-30 min , compared to a corresponding liquid form. 
     
     
         19 . The method of  claim 12 , wherein said pharmaceutical nasal dosage form upon intranasal administration to a human subject provides at least about 10% reduction in time required to achieve C max  or a plasma concentration of at least about 700 pg/ml, compared to a corresponding liquid form. 
     
     
         20 . The method of  claim 12 , wherein said pharmaceutical nasal dosage form upon intranasal administration to a human subject provides at least one of the following pharmacokinetic parameters: C max  of at least 900 pg/mL; AUC 0-t  of at least 1000 pg*hr/mL; and AUC 0-inf  of at least 5000 pg*hr/mL.