Method of using sustained release aminopyridine compositions

• US 8,354,437 B2
• Filed: 04/08/2005
• Issued: 01/15/2013
• Est. Priority Date: 04/09/2004
• Status: Active Grant

• Current Assignee: Acorda Therapeutics Incorporated
• Original Assignee: Acorda Therapeutics Incorporated
• Inventors: Blight, Andrew R., Cohen, Ron
• Primary Examiner(s): RAO, SAVITHA M
• Application Number:
  US11/102,559
• Publication Number:
  US 20050228030A1
• Time in Patent Office: 2,839 Days
• Field of Search: 514/352, 514/903, 514/965, 424/468
• US Class Current: 514/352
• CPC Class Codes: A61K 31/435 having six-membered rings with one nitrogen as the only ring hetero atom
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/4409 only substituted in position 4, e.g. isoniazid, iproniazid
• CPC Class Codes: A61K 9/20 Pills, tablets, discs, rods A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

A pharmaceutical composition which comprises a therapeutically effective amount of a aminopyridine dispersed in a release matrix, including, for example, a composition that can be formulated into a stable, sustained-release oral dosage formulation, such as a tablet which provides, upon administration to a patient, a therapeutically effective plasma level of the aminopyridine for a period of at about 12 hours and the use of the composition to treat various neurological diseases, including multiple sclerosis. A method of selecting individuals based on responsiveness to a treatment, including, for example, identifying individuals who responded to treatment with a sustained release fampridine composition.

Claims

1. A method of increasing walking speed in a human multiple sclerosis patient in need thereof comprising orally administering to said patient a sustained release composition of 10 milligrams of 4-aminopyridine twice daily for a time period of at least two weeks, wherein said 10 milligrams of 4-aminopyridine twice daily are the only doses of 4-aminopyridine administered to said patient during said time period.

5. The method of claim 1 wherein said time period comprises twelve weeks.

9. The method of claim 1 wherein said method comprises initiating treatment of said patient with 4-aminopyridine by orally administering said sustained release composition twice daily to said patient.

13. The method of claim 1 wherein twice daily is about every 12 hours.

17. The method of claim 5 wherein twice daily is about every 12 hours.

18. The method of claim 1 wherein said sustained release composition is a tablet.

22. The method of claim 18 wherein said tablet exhibits a release profile to obtain a C_avSS of about 15 ng/ml to about 35 ng/ml.

26. The method of claim 1 further comprising a step of measuring walking speed of the patient.

28. The method of claim 1 wherein said patient has relapsing remitting multiple sclerosis.

2. A method of improving walking in a human multiple sclerosis patient in need thereof comprising orally administering to said patient a sustained release composition of 10 milligrams of 4-aminopyridine twice daily for a time period of at least two weeks, wherein said 10 milligrams of 4-aminopyridine twice daily are the only doses of 4-aminopyridine administered to said patient during said time period.

6. The method of claim 2 wherein said time period comprises twelve weeks.

10. The method of claim 2 wherein said method comprises initiating treatment of said patient with 4-aminopyridine by orally administering said sustained release composition twice daily to said patient.

14. The method of claim 2 wherein twice daily is about every 12 hours.

19. The method of claim 2 wherein said sustained release composition is a tablet.

23. The method of claim 19 wherein said tablet exhibits a release profile to obtain a _CavSS of about 15 ng/ml to about 35 ng/ml.

29. The method of claim 2 wherein said patient has relapsing remitting multiple sclerosis.

3. A method of improving lower extremity muscle tone in a human multiple sclerosis patient in need thereof comprising orally administering to said patient a sustained release composition of 10 milligrams of 4-aminopyridine twice daily for a time period of at least two weeks, wherein said 10 milligrams of 4-aminopyridine twice daily are the only doses of 4-aminopyridine administered to said patient during said time period.

7. The method of claim 3 wherein said time period comprises twelve weeks.

11. The method of claim 3 wherein said method comprises initiating treatment of said patient with 4-aminopyridine by orally administering said sustained release composition twice daily to said patient.

15. The method of claim 3 wherein twice daily is about every 12 hours.

20. The method of claim 3 wherein said sustained release composition is a tablet.

24. The method of claim 20 wherein said tablet exhibits a release profile to obtain a C_avSS of about 15 ng/ml to about 35 ng/ml.

30. The method of claim 3 wherein said patient has relapsing remitting multiple sclerosis.

4. A method of improving lower extremity muscle strength in a human multiple sclerosis patient in need thereof comprising orally administering to said patient a sustained release composition of 10 milligrams of 4-aminopyridine twice daily for a time period of at least two weeks, wherein said 10 milligrams of 4-aminopyridine twice daily are the only doses of 4-aminopyridine administered to said patient during said time period.

8. The method of claim 4 wherein said time period comprises twelve weeks.

12. The method of claim 4 wherein said method comprises initiating treatment of said patient with 4-aminopyridine by orally administering said sustained release composition twice daily to said patient.

16. The method of claim 4 wherein twice daily is about every 12 hours.

21. The method of claim 4 wherein said sustained release composition is a tablet.

25. The method of claim 21 wherein said tablet exhibits a release profile to obtain a C_avSS of about 15 ng/ml to about 35 ng/ml.

27. The method of claim 4 further comprising a step of measuring lower extremity muscle strength of the patient.

31. The method of claim 4 wherein said patient has relapsing remitting multiple sclerosis.

32. A method of increasing walking speed in a human multiple sclerosis patient in need thereof comprising orally administering to said patient a sustained release tablet of 10 milligrams of 4-aminopyridine at about every 12 hours for a time period of at least two weeks, wherein said 10 milligrams of 4-aminopyridine at about every 12 hours are the only doses of 4-aminopyridine administered to said patient during said time period.

36. The method of claim 32 wherein said time period comprises twelve weeks.

33. A method of improving walking in a human multiple sclerosis patient in need thereof comprising orally administering to said patient a sustained release tablet of 10 milligrams of 4-aminopyridine at about every 12 hours for a time period of at least two weeks, wherein said 10 milligrams of 4-aminopyridine at about every 12 hours are the only doses of 4-aminopyridine administered to said patient during said time period.

37. The method of claim 33 wherein said time period comprises twelve weeks.

34. A method of improving lower extremity muscle tone in a human multiple sclerosis patient in need thereof comprising orally administering to said patient a sustained release tablet of 10 milligrams of 4-aminopyridine at about every 12 hours for a time period of at least two weeks, wherein said 10 milligrams of 4-aminopyridine at about every 12 hours are the only doses of 4-aminopyridine administered to said patient during said time period.

35. A method of improving lower extremity muscle strength in a human multiple sclerosis patient in need thereof comprising orally administering to said patient a sustained release tablet of 10 milligrams of 4-aminopyridine at about every 12 hours for a time period of at least two weeks, wherein said 10 milligrams of 4-aminopyridine at about every 12 hours are the only doses of 4-aminopyridine administered to said patient during said time period.

38. A method of treating walking disability in a human multiple sclerosis patient in need thereof comprising orally administering to said patient a sustained release composition of 10 milligrams of 4-aminopyridine twice daily for a time period of at least two weeks, wherein said 10 milligrams of 4-aminopyridine twice daily are the only doses of 4-aminopyridine administered to said patient during said time period.

39. The method of claim 38 wherein said method comprises orally administering to said patient a sustained release tablet of 10 milligrams of 4-aminopyridine at about every 12 hours for a time period of at least two weeks.

40. The method of claim 39 wherein said time period comprises 12 weeks.