COMPOSITIONS AND METHODS FOR TREATING AMYOTROPHIC LATERAL SCLEROSIS

• US 20110009460A1
• Filed: 06/21/2010
• Published: 01/13/2011
• Est. Priority Date: 06/19/2009
• Status: Abandoned Application

• Current Assignee: Knopp Biosciences LLC
• Original Assignee: Knopp Biosciences LLC
• Inventors: BOZIK, Michael E., GRIBKOFF, Valentin
• Application Number:
  US12/819,990
• Publication Number:
  US 20110009460A1
• Time in Patent Office: Days
• US Class Current: 514/367
• CPC Class Codes: A61K 31/428 condensed with carbocyclic rings
• CPC Class Codes: A61P 21/02 Muscle relaxants, e.g. for tetanus or cramps
• 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

Abstract

Pharmaceutical compositions of dexpramipexole and methods of using such compositions for the treatment of ALS are disclosed.

Claims

1. A method for treating amyotrophic lateral sclerosis (ALS) in a patient comprising:

administering to the patient an effective amount of about chirally pure (6R)-2-amino-4,5,6,7-tetrahydro-6-(propylamino)benzothiazole or pharmaceutically acceptable salt thereof.

2. The method of claim 1, wherein treating comprises slowing progression of amyotrophic lateral sclerosis (ALS), reducing intensity of symptoms associated with amyotrophic lateral sclerosis (ALS), reducing onset of symptoms associated with amyotrophic lateral sclerosis (ALS), reducing weight loss associated with amyotrophic lateral sclerosis (ALS), reversing weight loss associated with amyotrophic lateral sclerosis (ALS), delaying mortality, and combinations thereof.

3. The method of claim 2, wherein the symptoms associated with amyotrophic lateral sclerosis (ALS) are selected from group consisting of fine motor function, gross motor function, balbar function, respiratory function, and combinations thereof.

4. The method of claim 2, wherein the symptoms associated with amyotrophic lateral sclerosis (ALS) are selected from the group consisting of walking, speech, eating, swallowing, writing, climbing stairs, cutting food, turning in bed, salivation, dressing, maintaining hygiene, breathing, dyspnea, orthopnea, respiratory insufficiency, and combinations thereof.

5. The method of claim 1, wherein the effective amount is from about 50 mg to about 300 mg per day.

6. The method of claim 1, wherein the effective amount is from about 150 mg to about 300 mg per day.

7. The method of claim 1, wherein the effective amount is about 300 mg or more per day.

8. The method of claim 1, wherein administering comprises administering a dose equal to about half of the daily dose two times per day.

9. The method of claim 1, wherein administering comprises administering a dose equal to about half of a daily dose every 12 hours.

10. The method of claim 1, wherein administering comprises administering a dose equal to about one quarter of a daily dose four times per day.

11. The method of claim 1, wherein administering comprises administering about 150 mg two times per day.

12. The method of claim 1, wherein administering comprises administering about 75 mg four times per day.

13. The method of claim 1, wherein the method is carried out for a time period selected from the group consisting of at least about 12 weeks, at least about 6 months, at least about 1 year, at least about 2 years, at least about 3 years, at least about 4 years, at least about 5 years, at least about 10 years, and until the patient dies.

14. The method of claim 1, wherein the method is carried out at least daily for an indefinite amount of time.

15. The method of claim 1, further comprising administering one or more other ALS treatments simultaneously or concurrently with administering about chirally pure (6R)-2-amino-4,5,6,7-tetrahydro-6-(propylamino)benzothiazole or a pharmaceutically acceptable salt thereof.

16. The method of claim 15, wherein the one or more other ALS treatment includes riluzole.

17. The method of claim 1, wherein the patient began exhibiting symptoms of ALS less than about two years before beginning administering of (6R)-2-amino-4,5,6,7-tetrahydro-6-(propylamino)benzothiazole or pharmaceutically acceptable salt thereof.

18. The method of claim 1, wherein the patient began exhibiting symptoms of ALS at least greater than about two years before beginning administering of (6R)-2-amino-4,5,6,7-tetrahydro-6-(propylamino)benzothiazole or pharmaceutically acceptable salt thereof.

19. The method of claim 1, wherein the patient exhibits a greater than 20 % improvement in ALS Functional Rating Scale, Revised (ALSFRS-R) score when compared to baseline.

20. The method of claim 1, wherein the patient exhibits a greater than 30% improvement in ALS Functional Rating Scale, Revised (ALSFRS-R) score when compared to baseline.

21. The method of any one of claims 25 or 26, wherein the improvement is apparent in a time period selected from the group consisting of less than about 9 months, less than about 6 months, less than about 3 months, and less than about 1 month.

22. The method of claim 1, wherein administering about chirally pure (6R)-2-amino-4,5,6,7-tetrahydro-6-(propylamino)benzothiazole or pharmaceutically acceptable salt thereof results in slowing of a rate of fine motor function loss in the patient.

23. The method of claim 1, further comprising administering a daily dose of greater than an effective amount for a period of time before administering an effective amount of about chirally pure (6R)-2-amino-4,5,6,7-tetrahydro-6-(propylamino)benzothiazole or pharmaceutically acceptable salt thereof.

24. The method of claim 23, wherein the greater than an effective amount is greater than 150 mg.

25. The method of claim 23, wherein the greater than an effective amount is greater than 300 mg.

26. The method of claim 23, wherein the period of time before administering an effective amount is from about 1 weeks to about 12 weeks.

27. The method of claim 23, wherein the period of time before administering an effective amount is from about 2 weeks to about 6 weeks.

28. The method of claim 23, wherein administering an effective amount of about chirally pure (6R)-2-amino-4,5,6,7-tetrahydro-6-(propylamino)benzothiazole or pharmaceutically acceptable salt thereof is carried out indefinitely.

29. The method of claim 1, wherein an effective amount of about chirally pure (6R)-2-amino-4,5,6,7-tetrahydro-6-(propylamino)benzothiazole or pharmaceutically acceptable salt thereof is administered in an initial dose and every administration thereafter.

30. The method of claim 1, wherein dosing achieves a dose dependent, steady state AUC_0-12 (h×

ng/mL) selected from the group consisting of 836±

234 for an effective amount of 50 mg, 2803±

1635 for an effective amount of 150 mg, and 6004±

2700 for an effective amount of 300 mg.

31. The method of claim 1, wherein the effective amount comprises a stable daily dose.

32. The method of claim 31, wherein the stable daily dose comprises from about 50 mg to about 300 mg of about chirally pure (6R)-2-amino-4,5,6,7-tetrahydro-6-(propylamino)benzothiazole or pharmaceutically acceptable salt thereof.

33. The method of claim 31, wherein the stable daily dose comprises 1 to 5 unit doses per day.

34. The method of claim 33, wherein each unit dose is a solid unit dose.

35. The method of claim 31, wherein administering comprises administering one unit dose two times per day wherein each unit dose is equal to about half of the stable daily dose.

36. The method of claim 31, wherein administering comprises administering one unit dose once every 12 hours wherein each unit dose is equal to about half of the stable daily dose.

37. The method of claim 31, wherein administering comprises administering one unit dose four times per day wherein each unit dose is equal to about one quarter of the stable daily dose.

38. The method of claim 31, wherein administering comprises administering two unit doses wherein each unit dose is about 150 mg two times per day.

39. The method of claim 31, wherein administering comprises administering four unit doses wherein each unit dose is about 75 mg four times per day.

40. The method of claim 31, wherein administering a stable daily dose of about chirally pure (6R)-2-amino-4,5,6,7-tetrahydro-6-(propylamino)benzothiazole or pharmaceutically acceptable salt thereof is carried out for at least about 12 weeks.

41. The method of claim 39, wherein administering a stable daily dose of about chirally pure (6R)-2-amino-4,5,6,7-tetrahydro-6-(propylamino)benzothiazole or pharmaceutically acceptable salt thereof is carried out for an indefinite amount of time.

42. The method of claim 31, wherein the stable daily dose is consistent throughout a treatment regimen.

43. The method of claim 31, wherein an initial daily dose is equal to each daily dose thereafter.

44. The method of claim 31, wherein there is not titration before administering the stable daily dose.

45. The method of claim 31, wherein administering achieves a dose dependent, steady state AUC_0-12 (h×

ng/mL) selected from 836±

234 for stable daily dose of 50 mg, 2803±

1635 for stable daily dose of 150 mg, or 6004±

2700 for stable daily dose of 300 mg.

46. The method of claim 1, further comprising monitoring the patient.

47. The method of claim 1, further comprising monitoring the patient for neutropenia.

48. The method of claim 1, further comprising monitoring ALSFRS-R score for the patient.

49. The method of claim 1, further comprising monitoring the patients fine motor function, gross motor function, bulbar function, respiratory function, and combinations thereof.

50. The method of claim 1, further comprising monitoring behaviors selected from the group consisting of swallowing, handwriting, speech, ability to walk, ability to climb stairs, ability to dress, ability to maintain hygiene, and combinations thereof.

51. The method of claim 1, further comprising scheduling a doctor visit every 6 months for at least 12 months.

52. The method of claim 1, wherein the patient is predisposed to amyotrophic lateral sclerosis (ALS) and is not exhibiting symptoms of amyotrophic lateral sclerosis (ALS).

53. The method of claim 1, further comprising administering about chirally pure (6R)-2-amino-4,5,6,7-tetrahydro-6-(propylamino)benzothiazole or pharmaceutically acceptable salt thereof to family members of the patient.

54. The method of claim 1, wherein treating comprises administering the about chirally pure (6R)-2-amino-4,5,6,7-tetrahydro-6-(propylamino)benzothiazole or pharmaceutically acceptable salt thereof to a patient not exhibiting symptoms of amyotrophic lateral sclerosis (ALS).

55. The method of claim 1, wherein treating comprises administering the about chirally pure (6R)-2-amino-4,5,6,7-tetrahydro-6-(propylamino)benzothiazole or pharmaceutically acceptable salt thereof to a patient that is predisposed to amyotrophic lateral sclerosis (ALS).