Methods of using sustained release aminopyridine compositions

• US 8,440,703 B2
• Filed: 11/18/2011
• Issued: 05/14/2013
• 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:
  US13/299,969
• Publication Number:
  US 20120064007A1
• Time in Patent Office: 543 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 improving lower extremity function in a human multiple sclerosis patient in need thereof comprising orally administering to said patient a sustained release composition of less than 15 milligrams of 4-aminopyridine twice daily for a time period of at least two weeks, wherein the amount of said 4-aminopyridine administered to said patient in each said administering step is the same over said time period.

3. The method of claim 1, wherein the improving lower extremity function in the patient is increasing walking speed of the patient.

4. The method of claim 1, wherein the lower extremity function is lower extremity muscle strength.

5. The method of claim 1, wherein the lower extremity function is lower extremity muscle tone.

6. 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.

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

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

12. The method of claim 8, wherein said sustained release composition is a tablet.

14. The method of claim 1, wherein said sustained release composition provides a release profile to obtain a C_avSS of about 15 ng/ml to about 35 ng/ml.

16. The method of claim 1, wherein said sustained release composition provides a mean T_max in a range of about 2 to about 6 hours after administration of the sustained release composition to the patient.

18. The method of claim 1, wherein said sustained release composition provides a mean T_max in a range of about 2 to about 5.2 hours after administration of the sustained release composition to the patient.

20. The method of claim 1, wherein said sustained release composition is capable of providing, upon administration to the patient, a release profile of the 4-aminopyridine extending over at least 6 hours.

22. The method of claim 1, wherein said 4-aminopyridine is dispersed in a rate of release controlling polymer.

24. The method of claim 1, wherein said sustained release composition comprises a matrix, in which said 4-aminopyridine is uniformly dispersed, that is suitable for controlling the release rate of the 4-aminopyridine.

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

28. The method of claim 1, wherein said time period is more than two weeks.

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

32. The method of claim 1, wherein the lower extremity function is walking.

33. The method of claim 32, wherein said method comprises initiating treatment of said patient with 4-aminopyridine by orally administering said sustained release composition twice daily to said patient.

34. The method of claim 32, wherein said sustained release composition is a tablet, and wherein twice daily is about every 12 hours.

35. The method of claim 32, wherein said sustained release composition provides a release profile to obtain a C_avSS of about 15 ng/ml to about 35 ng/ml.

37. The method of claim 32, wherein said sustained release composition provides a mean _Tmax in a range of about 2 to about 6 hours after administration of the sustained release composition to the patient.

39. The method of claim 32, wherein said sustained release composition provides a mean T_max in a range of about 2 to about 5.2 hours after administration of the sustained release composition to the patient.

40. The method of claim 34, wherein said sustained release composition provides a mean T_max in a range of about 2 to about 5.2 hours after administration of the sustained release composition to the patient.

42. The method of claim 32, wherein said sustained release composition comprises a matrix, in which said 4-aminopyridine is uniformly dispersed, that is suitable for controlling the release rate of the 4-aminopyridine.

44. The method of claim 32, wherein said time period is more than two weeks.

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

47. The method of claim 40, wherein the lower extremity function is walking, and wherein said time period comprises twelve weeks.

48. The method of claim 32, wherein said sustained release composition is capable of providing, upon administration to the patient, a release profile of the 4-aminopyridine extending over at least 6 hours.

50. The method of claim 32, wherein said 4-aminopyridine is dispersed in a rate of release controlling polymer.

52. The method of claim 32, wherein said patient has relapsing remitting multiple sclerosis.

2. A method of improving lower extremity function 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.

7. 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.

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

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

13. The method of claim 9, wherein said sustained release composition is a tablet.

15. The method of claim 2, wherein said sustained release composition provides a release profile to obtain a C_avSS of about 15 ng/ml to about 35 ng/ml.

17. The method of claim 2, wherein said sustained release composition provides a mean T_max in a range of about 2 to about 6 hours after administration of the sustained release composition to the patient.

19. The method of claim 2, wherein said sustained release composition provides a mean T_max in a range of about 2 to about 5.2 hours after administration of the sustained release composition to the patient.

21. The method of claim 2, wherein said sustained release composition is capable of providing, upon administration to the patient, a release profile of the 4-aminopyridine extending over at least 6 hours.

23. The method of claim 2, wherein said 4-aminopyridine is dispersed in a rate of release controlling polymer.

25. The method of claim 2, wherein said sustained release composition comprises a matrix, in which said 4-aminopyridine is uniformly dispersed, that is suitable for controlling the release rate of the 4-aminopyridine.

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

29. The method of claim 2, wherein said time period is more than two weeks.

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

36. The method of claim 2, wherein the lower extremity function is walking, and wherein said sustained release composition provides a release profile to obtain a C_avSS of about 15 ng/ml to about 35 ng/ml.

38. The method of claim 2, wherein the lower extremity function is walking, and wherein said sustained release composition provides a mean T_max in a range of about 2 to about 6 hours after administration of the sustained release composition to the patient.

41. The method of claim 2, wherein the lower extremity function is walking, and wherein said sustained release composition provides a mean T_max in a range of about 2 to about 5.2 hours after administration of the sustained release composition to the patient.

43. The method of claim 2, wherein the lower extremity function is walking, and wherein said sustained release composition comprises a matrix, in which said 4-aminopyridine is uniformly dispersed, that is suitable for controlling the release rate of the 4-aminopyridine.

45. The method of claim 2, wherein the lower extremity function is walking, and wherein said time period is more than two weeks.

49. The method of claim 2, wherein the lower extremity function is walking, and wherein said sustained release composition is capable of providing, upon administration to the patient, a release profile of the 4-aminopyridine extending over at least 6 hours.

51. The method of claim 2, wherein the lower extremity function is walking, and wherein said 4-aminopyridine is dispersed in a rate of release controlling polymer.