Methods of treating dementia and pharmaceutical compositions thereof

Patent metadata

Field	Value
Publication number	US-10660878-B2
Application number	US-201715696880-A
Country	US
Kind code	B2
Filing date	Sep 6, 2017
Priority date	Sep 9, 2012
Publication date	May 26, 2020
Grant date	May 26, 2020

Abstract

The present invention describes methods of treating dementia comprising administering an effective daily dose of N-[2-(6-fluoro-1H-indol-3-yl)ethyl]-3-(2,2,3,3-tetrafluoropropoxy)benzylamine to improve or augment the effect of an acetylcholinesterase inhibitor.

First claim

What is claimed:

1. A method of treating Lewy Body dementia by improving or augmenting the effect of an acetylcholinesterase inhibitor comprising administering an effective daily dose of N-[2-(6-fluoro-1H-indol-3-yl)ethyl]-3-(2,2,3,3-tetrafluoropropoxy)benzylamine or a pharmaceutically acceptable salt thereof to a patient in need of such treatment, wherein the effective daily dose administered to the patient is between about 30 and about 60 mg.

2. A method of treating Lewy Body dementia as adjunctive therapy to treatment with an acetylcholinesterase inhibitor comprising administering an effective daily dose of N-[2-(6-fluoro-1H-indol-3-yl)ethyl]-3-(2,2,3,3-tetrafluoropropoxy)benzylamine or a pharmaceutically acceptable salt thereof to a patient in need of such treatment, wherein the effective daily dose administered to the patient is between about 30 and about 60 mg.

3. The method of claim 1 , wherein the patient is a human and the administered dose provides a blood plasma concentration of N-[2-(6-fluoro-1H-indol-3-yl)ethyl]-3-(2,2,3,3-tetrafluoropropoxy)benzylamine in a range of about 56 ng/mL to about 310 ng/mL at steady-state plasma level.

4. The method of claim 1 , wherein the patient is a human and the administered dose provides a receptor occupancy of N-[2-(6-fluoro-1H-indol-3-yl)ethyl]-3-(2,2,3,3-tetrafluoropropoxy)benzylamine greater than or equal to about 90% at the 5HT-6 receptor at a steady-state plasma level.

5. The method of claim 2 , wherein the patient is a human and the administered dose provides a blood plasma concentration of N-[2-(6-fluoro-1H-indol-3-yl)ethyl]-3-(2,2,3,3-tetrafluoropropoxy)benzylamine in a range of about 56 ng/mL to about 310 ng/mL at steady-state plasma level.

6. The method of claim 2 , wherein the patient is a human and the administered dose provides a receptor occupancy of N-[2-(6-fluoro-1H-indol-3-yl)ethyl]-3-(2,2,3,3-tetrafluoropropoxy)benzylamine greater than or equal to about 90% at the 5HT-6 receptor at a steady-state plasma level.

7. The method of claim 1 , wherein the pharmaceutically acceptable salt is the hydrochloride.

8. The method of claim 1 , wherein the dose is administered as an immediate release formulation.

9. The method of claim 1 , wherein the acetylcholinesterase inhibitor is donepezil.

10. The method of claim 1 , wherein the acetylcholinesterase inhibitor is rivastigmine.

11. The method of claim 1 , wherein the effective daily dose is about 30 mg.

12. The method of claim 1 , wherein the effective daily dose is about 40 mg or less.

13. The method of claim 1 , wherein the effective daily dose is about 50 mg or less.

14. The method of claim 1 , wherein the effective daily dose is about 60 mg or less.

15. The method of claim 2 , wherein the pharmaceutically acceptable salt is the hydrochloride.

16. The method of claim 2 , wherein the dose is administered as an immediate release formulation.

17. The method of claim 2 , wherein the acetylcholinesterase inhibitor is donepezil.

18. The method of claim 2 , wherein the acetylcholinesterase inhibitor is rivastigmine.

19. The method of claim 2 , wherein the effective daily dose is about 30 mg.

20. The method of claim 2 , wherein the effective daily dose is about 40 mg or less.

21. The method of claim 2 , wherein the effective daily dose is about 50 mg or less.

22. The method of claim 2 , wherein the effective daily dose is about 60 mg or less.

Assignees

• H Lundbeck As

Inventors

• Schmidt Ellen
• Areberg Johan

Classifications

• A61K9/0053

  Mouth and digestive tract, i.e. intraoral and peroral administration · CPC title

• A61K31/445

  Non condensed piperidines, e.g. piperocaine · CPC title

• A61K45/06 Primary

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K31/55

  having seven-membered rings, e.g. azelastine, pentylenetetrazole · CPC title

• A61K31/27

  of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine · CPC title