Dosing Regimens for Treating And/Or Preventing Cerebral Amyloidoses

• US 20160008383A1
• Filed: 04/13/2015
• Published: 01/14/2016
• Est. Priority Date: 04/14/2014
• Status: Active Grant

• Current Assignee: Amicus Therapeutics, Inc.
• Original Assignee: Amicus Therapeutics, Inc.
• Inventors: Wustman, Brandon Alan
• Granted Patent: US 9,675,627 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• 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

Described herein are dosing regimens and kits for the treatment and/or prevention of cerebral amyloidoses such as Alzheimer'"'"'s disease (AD) and/or cerebral amyloid angiopathy (CAA).

Claims

1. A method for preventing and/or treating Alzheimer'"'"'s disease and/or cerebral amyloid angiopathy in a patient at risk for developing or diagnosed with the same, the method comprising:

administering to the patient an effective amount of 2-acetamido-1,2-dideoxynojirimycin (AdDNJ) for a first enzyme enhancement period;

not administering the AdDNJ for a substrate turnover period; and

then

administering to the patient an effective amount of AdDNJ for a second enzyme enhancement period.

2. The method of claim 1, wherein the first enzyme enhancement period and the second enzyme enhancement period have the same duration.

3. The method of claim 1, wherein one or more of the first enzyme enhancement period and the second enzyme enhancement period is a period of about 1 day to about 8 days.

4. The method of claim 2, wherein one or more of the first enzyme enhancement period and the second enzyme enhancement period is a period of about 4 days to about 6 days.

5. The method of claim 1, wherein the AdDNJ is administered daily during the first enzyme enhancement period and the second enzyme enhancement period.

6. The method of claim 1, wherein the AdDNJ is administered orally.

7. The method of claim 1, wherein the AdDNJ is administered at a dose in the range of about 3 mg/kg/day to about 300 mg/kg/day.

8. The method of claim 7, wherein the AdDNJ is administered at a dose of about 100 mg/kg/day.

9. The method of claim 1, wherein not administering the AdDNJ for the substrate turnover period comprises not administering AdDNJ for a period of about 48 hours to about 96 hours.

10. The method of claim 9, wherein not administering the AdDNJ for the substrate turnover period comprises not administering AdDNJ for a period of about 72 hours.

11. The method of claim 1, wherein the first enzyme enhancement period is about 5 days and not administering the AdDNJ for the substrate turnover period comprises not administering AdDNJ for a period of about 72 hours.

12. The method of claim 1, wherein the method comprises:

administering to the patient an effective amount of AdDNJ on a first day;

not administering the AdDNJ on a second day;

administering to the patient an effective amount of AdDNJ on a third day;

not administering the AdDNJ on a fourth day;

administering to the patient an effective amount of AdDNJ on a fifth day; and

then not administering the AdDNJ for a period of about 72 hours

13. The method of claim 1, wherein not administering the AdDNJ for a substrate turnover period comprises not administering AdDNJ for a period of about 24 hours.

14. The method of claim 1, wherein not administering the AdDNJ for a substrate turnover period comprises not administering AdDNJ for a period of about 48 hours.

15. The method of claim 1, wherein the first enzyme enhancement period is about 3 days and not administering the AdDNJ for the substrate turnover period comprises not administering AdDNJ for a period of about 120 hours.

16. The method of claim 1, wherein the method comprises alternating between enzyme enhancement periods and substrate turnover periods for a total treatment time of at least 1 month.

17. The method of claim 16, wherein the total treatment time is at least 3 months.

18. The method of claim 16, wherein at least one substrate turnover period has a different duration than at least one other substrate turnover period.

19. A kit comprising:

one or more dosage forms comprising an effective amount of 2-acetamido-1,2-dideoxynojirimycin (AdDNJ); and

instructions for;

administering the dosage forms for a first enzyme enhancement period;

not administering the dosage forms for a substrate turnover period; and

then

administering the dosage forms for a second enzyme enhancement period.

20. The kit of claim 19, wherein the first enzyme enhancement period and the second enzyme enhancement period have the same duration.

21. The kit of claim 19, wherein one or more of the first enzyme enhancement period and the second enzyme enhancement period is a period of about 1 day to about 8 days.

22. The kit of claim 19, wherein not administering the AdDNJ for the substrate turnover period comprises not administering AdDNJ for a period of about 48 hours to about 96 hours.

23. A kit comprising:

one or more active dosage forms comprising an effective amount of 2-acetamido-1,2-dideoxynojirimycin (AdDNJ);

one or more inactive dosage forms that do not comprise an effective amount of AdDNJ; and

instructions for;

administering the active dosage forms for a first enzyme enhancement period;

administering the inactive dosage forms for a substrate turnover period; and

then

administering the active dosage forms for a second enzyme enhancement period.

24. The kit of claim 23, wherein the first enzyme enhancement period and the second enzyme enhancement period have the same duration.

25. The kit of claim 23, wherein one or more of the first enzyme enhancement period and the second enzyme enhancement period is a period of about 1 day to about 8 days.

26. The kit of claim 23, wherein not administering the AdDNJ for the substrate turnover period comprises not administering AdDNJ for a period of about 48 hours to about 96 hours.