METHOD OF THERAPEUTIC ADMINISTRATION OF DHE TO ENABLE RAPID RELIEF OF MIGRAINE WHILE MINIMIZING SIDE EFFECT PROFILE

• US 20100284940A1
• Filed: 07/19/2010
• Published: 11/11/2010
• 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., Armer, Thomas A., Ramadan, Nabih N., Shrewsbury, Stephen B.
• Granted Patent: US 8,119,639 B2
• Time in Patent Office: Days
• US Class Current: 424/46
• 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 comprising:

administering a total dose of dihydroergotamine, or a complex, chelate, salt, hydrate, polymorph, or ion pair thereof to a human suffering from migraine;

wherein the dihydroergotamine, or a complex, chelate, salt, hydrate, polymorph, or ion pair thereof is administered at such a rate that a mean peak plasma concentration (C_max) of dihydroergotamine thereof is less than 60,000 pg/ml;

a mean time to C_max (T_max) of dihydroergotamine is less than 20 minutes; and

wherein the total dose of dihydroergotamine, or a complex, chelate, salt, hydrate, polymorph, or ion pair thereof ranges from 0.1 to 10 mg per migraine.

21. The method of claim 1, wherein the mean peak plasma concentration (C_max) of dihydroergotamine thereof is less than 40,000 pg/ml.

22. The method of claim 21, wherein the mean peak plasma concentration (C_max) of dihydroergotamine thereof is less than 20,000 pg/ml.

23. The method of claim 22, wherein the mean peak plasma concentration (C_max) of dihydroergotamine thereof is less than 15,000 pg/ml.

24. The method of claim 1, wherein the mean T_max of dihydroergotamine is within 15 minutes following administration.

29. The method of claim 1, wherein the total dose ranges from 0.5 mg to 5.0 mg per migraine.

38. The method of claim 1, wherein the dihydroergotamine, or a complex, chelate, salt, hydrate, polymorph, or ion pair thereof is administered via intravenous, intra-arterial, intraperitoneal, intrapulmonary, oral, sublingual, buccal, intranasal, oral inhalation, intravesicular, intramuscular, intra-tracheal, subcutaneous, iontophoretic, or transdermal delivery.

39. The method of claim 1, wherein the dihydroergotamine, or a complex, chelate, salt, hydrate, polymorph, or ion pair thereof is administered by oral inhalation by a device comprising a dry powder inhaler, nebulizer, vaporizer, pressurized metered dose inhaler, or breath activated pressurized metered dose inhaler.

40. The method of claim 39, wherein the dihydroergotamine, or a complex, chelate, salt, hydrate, polymorph, or ion pair thereof is administered by a device comprising a breath activated pressurized metered dose inhaler.

41. The method of claim 38, wherein the dihydroergotamine, or a complex, chelate, salt, hydrate, polymorph, or ion pair thereof is administered via intrapulmonary delivery.

43. The method of claim 39, wherein the dihydroergotamine, or a complex, chelate, salt, hydrate, polymorph, or ion pair thereof is administered by a device comprising a dry powder inhaler.

53. The method of claim 40, wherein the breath activated pressurized metered dose inhaler comprises a plume control feature.

54. The method of claim 40, wherein the breath activated pressurized metered dose inhaler comprises a vortexing chamber.

55. The method of claim 1, wherein the total dose ranges from 1.0 mg to 2.0 mg per migraine.

56. The method of claim 1, wherein the dihydroergotamine, or a complex, chelate, salt, hydrate, polymorph, or ion pair thereof comprises dihydroergotamine mesylate.

57. The method of claim 1, wherein the human suffering from migraine is suffering from a migraine with aura.

2-20. -20. (canceled)

25-28. -28. (canceled)

30. A method comprising:

administering a unit dose of dihydroergotamine, or a complex, chelate, salt, hydrate, polymorph, or ion pair thereof to a human suffering from migraine;

wherein the dihydroergotamine, or a complex, chelate, salt, hydrate, polymorph, or ion pair thereof is administered at a rate such that a mean time to C_max (T_max) of dihydroergotamine is less than 20 minutes, and a mean under a curve of a concentration of dihydroergotamine in systemic circulation versus time (AUC) of the dihydroergotamine delivered is within 75% of a comparable intravenous (IV) delivered dose; and

wherein the unit dose of dihydroergotamine, or a complex, chelate, salt, hydrate, polymorph, or ion pair thereof is less than 2.0 mg.

31-37. -37. (canceled)

42. (canceled)

44-52. -52. (canceled)