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 method for treating migraine headache,
 comprising delivering a pharmaceutical nasal dosage form in a nasal device in one puff to each nostril of a human subject,   wherein the pharmaceutical nasal dosage form comprises: about 1.5 mg of dihydroergotamine or a pharmaceutically acceptable salt thereof; and at least one pharmaceutically acceptable excipient, and   wherein the delivering provides in the human subject:   (a) a mean time to C max  (T max ) of dihydroergotamine of about 30 minutes or about 35 minutes, and   (b) at least one of: a mean plasma peak concentration (C max ) of dihydroergotamine of at least about 0.7 ng/ml; and a mean plasma AUC 0-inf  of dihydroergotamine of at least about 3 ng*hr/ml,   as determined from measurement of a plasma concentration of dihydroergotamine by an LC/MS/MS analytical method.   
     
     
         2 . The method of  claim 1 , wherein the puff is in a liquid form. 
     
     
         3 . The method of  claim 1 , wherein the method treats acute migraine. 
     
     
         4 . The method of  claim 1 , wherein the method treats migraine with aura. 
     
     
         5 . The method of  claim 1 , wherein the method treats migraine without aura. 
     
     
         6 . The method of  claim 1 , wherein the pharmaceutical nasal dosage form comprises the pharmaceutically acceptable salt of dihydroergotamine. 
     
     
         7 . The method of  claim 1 , wherein the pharmaceutical nasal dosage form comprises the pharmaceutically acceptable salt of dihydroergotamine that is dihydroergotamine mesylate. 
     
     
         8 . The method of  claim 1 , wherein the pharmaceutical nasal dosage form further comprises caffeine. 
     
     
         9 . The method of  claim 1 , wherein the delivering provides in the human subject a mean plasma C max  of dihydroergotamine of at least about 1 ng/ml. 
     
     
         10 . The method of  claim 1 , wherein the delivering provides in the human subject a mean plasma AUC 0-inf  of dihydroergotamine of at least about 4 ng*hr/ml. 
     
     
         11 . The method of  claim 1 , wherein the delivering provides in the human subject a mean plasma AUC 0-inf  of dihydroergotamine of at least about 5 ng*hr/ml. 
     
     
         12 . The method of  claim 1 , wherein the delivering provides in the human subject a mean plasma AUC 0-inf  of dihydroergotamine of at least about 6 ng*hr/ml. 
     
     
         13 . The method of  claim 1 , wherein:
 the puff is in a liquid form;   the method treats acute migraine with or without aura;   the pharmaceutical nasal dosage form comprises the pharmaceutically acceptable salt of dihydroergotamine that is dihydroergotamine mesylate;   the pharmaceutical nasal dosage form further comprises caffeine; and   the delivering provides in the human subject a mean plasma C max  of dihydroergotamine of at least about 1 ng/ml and a mean plasma AUC 0-inf  of dihydroergotamine of at least about 6 ng*hr/ml.   
     
     
         14 . A method for treating migraine,
 comprising delivering a pharmaceutical nasal dosage form in a nasal device in one puff to each nostril of a human subject,   wherein the nasal device requires no priming to intranasally administer an effective dose and contains the pharmaceutical nasal dosage form that comprises: about 0.1 to about 1 mg of dihydroergotamine or a pharmaceutically acceptable salt thereof; and at least one pharmaceutically acceptable excipient, and   wherein the delivering provides in the human subject at least one of:   (a) a mean plasma peak concentration (C max ) of dihydroergotamine of at least about 0.7 ng/ml; and   (b) a mean plasma AUC 0-inf  of dihydroergotamine of at least about 3 ng*hr/ml, as determined from measurement of a plasma concentration of dihydroergotamine by an LC/MS/MS analytical method.   
     
     
         15 . The method of  claim 14 , wherein the puff is in a liquid form. 
     
     
         16 . The method of  claim 14 , wherein the delivering provides in the human subject a mean time to C max  (T max ) of dihydroergotamine of about 45 minutes. 
     
     
         17 . The method of  claim 14 , wherein the delivering provides in the human subject a mean plasma C max  of dihydroergotamine of at least about 0.9 ng/ml. 
     
     
         18 . The method of  claim 14 , wherein the delivering provides in the human subject a mean plasma AUC 0-inf  of dihydroergotamine of at least about 4 ng*hr/ml. 
     
     
         19 . The method of  claim 14 , wherein the delivering provides in the human subject a mean plasma AUC 0-inf  of dihydroergotamine of at least about 5 ng*hr/ml. 
     
     
         20 . The method of  claim 14 , wherein:
 the puff is in a liquid form; and   the delivering provides in the human subject a mean plasma C max  of dihydroergotamine of at least about 0.9 ng/ml; and a mean plasma AUC 0-inf  of dihydroergotamine of at least about 5 ng*hr/ml.