Droxidopa and pharmaceutical composition thereof for the treatment of fibromyalgia

• US 8,008,285 B2
• Filed: 03/07/2008
• Issued: 08/30/2011
• Est. Priority Date: 03/09/2007
• Status: Active Grant

• Current Assignee: Chelsea Therapeutics, Inc. (Lundbeck Foundation)
• Original Assignee: Chelsea Therapeutics, Inc. (Lundbeck Foundation)
• Inventors: Roberts, Michael J., Pedder, Simon
• Primary Examiner(s): Sznaidman; Marcos L
• Application Number:
  US12/044,680
• Publication Number:
  US 20080221170A1
• Time in Patent Office: 1,271 Days
• Field of Search: 514/183, 514/567, 514/619
• US Class Current: 514/183
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/195 having an amino group
• CPC Class Codes: A61K 31/198 Alpha-amino acids, e.g. alanine or edetic acid [EDTA] betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00
• CPC Class Codes: A61K 31/277 having a ring, e.g. verapamil
• CPC Class Codes: A61K 31/435 having six-membered rings with one nitrogen as the only ring hetero atom
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/14 Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
• CPC Class Codes: A61P 19/04 for non-specific disorders of the connective tissue
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present invention provides methods of treating fibromyalgia or other diseases or conditions causing widespread pain and/or fatigue. In particular, the invention provides pharmaceutical compositions comprising droxidopa alone, or in combination with one or more further active agents, that can be used in the inventive methods. The methods of treatment can comprise treating, preventing, reducing, or eliminating a variety of symptoms recognized as indicative of fibromyalgia, such as chronic pain, allodynia, hyperalgesia, fatigue, sleep disturbance, and depression.

Claims

1. A method for reducing pain associated with fibromyalgia, the method comprising administering a therapeutically effective amount of droxidopa to a patient suffering from fibromyalgia.

2. The method of claim 1, wherein the fibromyalgia-associated pain is reduced by at least 50%.

3. The method of claim 1, wherein the fibromyalgia-associated pain is reduced by at least 60%.

4. The method of claim 1, further comprising administering one or more additional active agents selected from the group consisting of DOPA decarboxylase inhibiting compounds, catechol-O-methyltransferase inhibitors, cholinesterase inhibitors, antidepressants, anti-inflammatories, muscle relaxants, antibiotics, mood stabilizers, antipsychotics, serotonin receptor antagonists, serotonin receptor agonists, pain relievers, stimulants, NMDA receptor ligands, s-adenosyl-methionine, zopiclone, chlormezanone, proglumetacin, 5-OH-L-tryptophan, gabapentin, pregabalin, tamoxefin, and combinations thereof.

5. The method of claim 4, wherein the one or more additional active agents comprise one or more DOPA decarboxylase inhibiting compounds selected from the group consisting of benserazide, carbidopa, difluoromethyldopa, α

-methyldopa, and combinations thereof.

6. The method of claim 4, wherein the one or more additional active agents comprise one or more catechol-O-methyltransferase inhibitors selected from the group consisting of entacapone, tolcapone, nitecapone, and combinations thereof.

7. The method of claim 4, wherein the one or more additional active agents comprise one or more cholinesterase inhibitors selected from the group consisting of pyridostigmine, donepezil, rivastigmine, galantamine, tacrine, neostigmine, metrifonate, physostigmine, ambenonium, edrophonium, demarcarium, thiaphysovenine, phenserine, cymserine, and combinations thereof.

8. The method of claim 4, wherein the one or more additional active agents comprise one or more antidepressants, wherein the antidepressant is a monoamine oxidase inhibitor selected from the group consisting of isocarboxazid, moclobemide, phenelzine, tranylcypromine, selegiline, lazabemide, nialamide, iproniazid, iproclozide, toloxatone, harmala, brofaromine, benmoxin, 5-Methoxy-N,N-dimethyltryptamine, 5-methoxy-α

-methyltryptamine, and combinations thereof.

9. The method of claim 4, wherein the one or more additional active agents comprise one or more antidepressants selected from the group consisting of selective serotonin reuptake inhibitors, tricyclics, serotonin norepinephrine reuptake inhibitors, norepinephrine reuptake inhibitors, norepinephrine and dopamine reuptake inhibitors, and combinations thereof.

10. The method of claim 9, wherein the antidepressants are selected from the group consisting of fluoxetine, paroxetine, citalopram, escitalopram, fluvoxamine, sertraline, amitriptyline, nortriptyline, desipramine, trazodone, venlafaxine, duloxetine, milnacipran, nefopam, bupropion, and combinations thereof.

11. The method of claim 4, wherein the one or more additional active agents are formulated in the same pharmaceutical composition with droxidopa.

12. The method of claim 4, wherein the one or more additional active agents are administered in a pharmaceutical composition separate from droxidopa.

13. The method of claim 1, comprising administering the droxidopa in combination with a DOPA decarboxylase inhibiting compound.

14. The method of claim 13, comprising administering the droxidopa in combination with carbidopa.

15. The method of claim 13, wherein the DOPA decarboxylase inhibiting compound is formulated in the same pharmaceutical composition with the droxidopa.

16. The method of claim 13, wherein the DOPA decarboxylase inhibiting compound is administered in a pharmaceutical composition separate from the droxidopa.

17. The method of claim 1, wherein the droxidopa is administered once daily.

18. The method of claim 1, wherein the droxidopa is administered twice daily.

19. The method of claim 1, wherein the droxidopa is administered three times daily.

20. The method of claim 1, wherein the droxidopa is administered as a sustained-release composition.