Method of therapeutic administration of DHE to enable rapid relief of migraine while minimizing side effect profile

• US 10,172,853 B2
• Filed: 03/28/2017
• Issued: 01/08/2019
• Est. Priority Date: 02/11/2007
• Status: Active Grant

• Current Assignee: MAP Pharmaceuticals, Inc. (Abbvie Incorporated)
• Original Assignee: MAP Pharmaceuticals, Inc. (Abbvie Incorporated)
• Inventors: Cook, Robert O., Shrewsbury, Stephen B., Ramadan, Nabih N., Armer, Thomas A.
• Primary Examiner(s): Anderson, James D
• Application Number:
  US15/471,334
• Publication Number:
  US 20170196861A1
• Time in Patent Office: 651 Days
• CPC Class Codes: A61K 31/10 Sulfides; Sulfoxides; Sulfones
• CPC Class Codes: A61K 31/48 Ergoline derivatives, e.g. lysergic acid, ergotamine
• CPC Class Codes: A61K 31/4985 Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
• CPC Class Codes: A61K 9/0073 Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M
• CPC Class Codes: A61K 9/0075 for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Pharmaceutical compositions containing dihydroergotamine (DHE) and methods in which DHE is administered to patients for treatment of migraine without side effects or adverse effects are disclosed. Methods for rapid treatment of migraine with DHE are disclosed comprising: dampening the peak plasma concentration (C_max) and slightly delaying the peak such as to avoid activating the dopaminergic and adrenergic receptors, while achieving sufficient active binding to the serotonin receptors to provide relief from migraine symptoms within a timeframe that permits rapid resolution of migraine symptoms. Inhaler devices suitable for the methods are disclosed. Kits for practicing the methods of invention are disclosed.

Claims

1. A method of providing migraine therapy to a human subject while minimizing one or more drug-induced side effects, said method comprising:

administering via pulmonary administration by oral inhalation a total dose of less than 3.0 mg of dihydroergotamine, or a salt thereof, to the human subject, wherein the dihydroergotamine, or the salt thereof, is administered at a rate that provides a mean peak plasma concentration (C_max) of dihydroergotamine of less than 20,000 pg/ml within a mean time to C_max (T_max) that is less than 20 minutes after the administration;

wherein the migraine therapy is prophylactic.

2. The method of claim 1, wherein the human subject has at least 2 to 4 headaches per month.

3. The method of claim 2, wherein the at least 2 to 4 headaches per month are severe enough to interfere with daily activity.

4. The method of claim 1, wherein the total dose of the dihydroergotamine, or the salt thereof, ranges from 1.0 mg to 2.0 mg.

5. The method of claim 1, wherein the one or more side effects is selected from the group consisting of nausea, emesis, vasospasm, paresthesia, hypertension, dizziness, anxiety, dyspnea, headache, flushing, diarrhea, rash, increased sweating, cardiac valvulopathy, pleural and retroperitoneal fibrosis, adverse cardiovascular effect, blood pressure instability and arterial constriction.

6. The method of claim 5, wherein the one or more side effects is selected from the group consisting of nausea, emesis, paresthesia and dizziness.

7. The method of claim 6, wherein the one or more side effects is nausea, emesis or both.

8. The method of claim 6, wherein the side effect is nausea.

9. The method of claim 6, wherein the side effect is emesis.

10. The method of claim 6, wherein the side effect is paresthesia.

11. The method of claim 6, wherein the side effect is dizziness.

12. The method of claim 1, wherein the C_max of the dihydroergotamine is less than 15,000 pg/ml.

13. The method of claim 1, wherein the C_max of the dihydroergotamine is less than 10,000 pg/ml.

14. The method of claim 1, wherein the C_max of the dihydroergotamine is less than 7,500 pg/ml.

15. The method of claim 1, wherein the dihydroergotamine, or the salt thereof, is administered by a pressurized metered dose inhaler (pMDI).

16. The method of claim 15, wherein the pMDI is a breath-activated pMDI.

17. The method of claim 1, wherein the dihydroergotamine, or the salt thereof, is administered without administering an anti-emetic to the human subject.