Methods of treating agitation and other dementia-associated behavioral symptoms

11865,119

18/177188

March 02, 2023

The invention is based on the discovery that rho kinase inhibitors, particularly fasudil can be used to treat agitation/anxiety in dementia patients, particularly Alzheimer's disease patients. Fasudil treatment of Alzheimer's patients resulted in improvements in agitation that are orders of magnitude to that observed with other potential therapeutic agents.

Woolsey Pharmaceuticals, Inc. (St. Petersburg, FL, US)

WOOLSEY PHARMACEUTICALS, INC. (St. Petersburg, FL, US)

1. A method of treating agitation in an Alzheimer's disease dementia patient, comprising orally administering to the patient a therapeutically effective amount of fasudil at a dose of 90 mg to 240 mg per day in an immediate release formulation, wherein the patient before treatment has a minimum score on the Cohen-Mansfield Agitation Index (CMAI) of ≥20, and wherein the patient treated with fasudil exhibits an improvement on the CMAI of at least 5 points from the patient's score before treatment with fasudil.

2. The method according to claim 1 , wherein the agitation comprises aggression, hostility, delusions, hallucinations, suspiciousness, insomnia, or aberrant motor behaviors.

3. The method according to claim 1 , wherein the fasudil is fasudil hydrochloride hemihydrate.

4. The method according to claim 3 , wherein the patient is administered a total daily dose of 90 mg fasudil hydrochloride hemihydrate at 30 mg TID.

5. The method according to claim 1 , where the patient is displaying at least one type of agitation as measured by the CMAI-C selected from the group consisting of physically aggressive, verbally aggressive, physically non-aggressive, and verbally non-aggressive.

6. The method according to claim 1 , wherein the patient treated with fasudil exhibits an improvement on the CMAI-C of at least about 12 points from the patient's baseline score before treatment with fasudil.

7. A method of treating agitation in an Alzheimer's disease dementia patient, comprising orally administering to the patient a therapeutically effective amount of fasudil at a dose of 90 mg to 240 mg per day in an immediate release formulation, wherein the patient before treatment has a minimum Neuropsychiatric Inventory-Questionnaire (NPI-Q) agitation/aggression domain score of ≤4.

8. The method according to claim 7 , wherein the patient treated with fasudil exhibits an improvement on the NPI-Q agitation/aggression domain of at least about 1 point to at least about 3 points from the patient's baseline score before treatment with fasudil.

9. The method according to claim 1 , wherein the fasudil treatment reduces the number of occurrences of agitation over a time period.

10. The method according to claim 9 , wherein the fasudil treatment reduces occurrences of agitation per day.

11. The method according to claim 9 , wherein the fasudil treatment reduces the number of days per week agitation occurs.

12. The method according to claim 9 , wherein the fasudil treatment reduces the number of occurrences of agitation per week.

13. The method according to claim 1 , wherein the fasudil treatment delays the increase in agitation that occurs in dementia patients as the severity of dementia progresses.

14. The method according to claim 1 , wherein the patient does not exhibit wandering behavior consisting of elopement, boundary transgressions, or wayfinding defects.

15. The method according to claim 1 , wherein the patient does not exhibit pacing, looping, or excessive walking.

16. The method according to claim 1 , wherein the patient has not previously been treated with fasudil for chronic stroke.

17. The method according to claim 7 , wherein the patient before treatment has a minimum Neuropsychiatric Inventory-Questionnaire (NPI-Q) agitation/aggression domain score of ≥6.

18. The method according to claim 7 , wherein the fasudil treatment reduces the lumber of occurrences of agitation over a time period.

19. The method according to claim 18 , wherein the fasudil treatment reduces occurrences of agitation per day.

20. The method according to claim 18 , wherein the fasudil treatment reduces the number of days per week agitation occurs.

21. The method according to claim 18 , wherein the fasudil treatment reduces the number of occurrences of agitation per week.

22. The method according to claim 7 , wherein the fasudil treatment delays the increase in agitation that occurs in dementia patients as the severity of dementia progresses.

23. The method according to claim 7 , wherein the patient does not exhibit wandering behavior consisting of elopement, boundary transgressions, or wayfinding defects.

24. The method according to claim 7 , wherein the patient does not exhibit pacing, looping, or excessive walking.

25. The method according to claim 7 , wherein the patient has not previously been treated with fasudil for chronic stroke.

26. The method according to claim 1 , wherein the fasudil treatment reduces the length of time, or the severity, of early evening agitation.

27. The method according to claim 7 , wherein the fasudil treatment reduces the length of time, or the severity, of early evening agitation.

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