COMBINATION OF PIMAVANSERIN AND CYTOCHROME P450 MODULATORS

• US 20190240211A1
• Filed: 03/23/2017
• Published: 08/08/2019
• Est. Priority Date: 03/25/2016
• Status: Active Grant

• Current Assignee: Acadia Pharmaceuticals Inc.
• Original Assignee: Acadia Pharmaceuticals Inc.
• Inventors: Parkinson, Andrew
• Granted Patent: US 10,953,000 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/4468 having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• 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: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• 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

A method for treating a disease or disorder in a patient who is currently taking a cytochrome P450 inhibitor comprising administering to the patient a dose of pimavanserin or a pharmaceutical acceptable salt thereof, wherein the dose is at least 20% lower than a dose of pimavanserin or a pharmaceutical acceptable salt thereof that would otherwise have been recommended to the patient if the patient were not currently taking the cytochrome P450 inhibitor.

Claims

1. A method for treating a disease or disorder in a patient who is currently taking a cytochrome P450 inhibitor comprising administering to the patient a dose of a compound of Formula (I) or a pharmaceutical acceptable salt thereof:

2. The method of claim 1, wherein the disease or disorder is Parkinson'"'"'s disease psychosis (PDP).

3. The method of claim 1, wherein the disease or disorder is Alzheimer'"'"'s disease psychosis (ADP).

4. The method of claim 2, wherein the disease or disorder is associated with hallucinations or delusions.

5. The method of claim 1, wherein the disease or disorder is schizophrenia.

6. The method of claim 1, wherein the cytochrome P450 inhibitor is a cytochrome P450 3A (CYP3A) inhibitor.

7. The method of claim 1, wherein the cytochrome P450 inhibitor is a cytochrome P450 3A4 (CYP3A4) inhibitor.

8. The method of claim 1, wherein the cytochrome P450 inhibitor is a cytochrome P450 3A5 (CYP3A5) inhibitor.

9. The method of claim 1, wherein the cytochrome P450 inhibitor is a moderate inhibitor of the cytochrome P450.

10. The method of claim 9, wherein the moderate inhibitor is selected from the group consisting of Aprepitant, Atazanavir/Ritonavir, Ciprofloxacin, Darunavir/Ritonavir, Diltiazem, Dronedarone, Erythromycin, Fluconazole, Grapefruit Juice, Imatinib, and Verapamil.

11. The method of claim 1, wherein the cytochrome P450 inhibitor is a strong inhibitor of the cytochrome P450.

12. The method of claim 11, wherein the strong inhibitor is selected from the group consisting of Boceprevir, Clarithromycin, Cobicistat, Conivaptan, Indinavir, Itraconazole, Ketoconazole, Lopinavir/Ritonavir, Mibefradil, Nefazodone, Nelfinavir, Posaconazole, Ritonavir, Saquinavir, Telaprevir, Telithromycin, Troleandomycing and Voriconazole.

13. The method of claim 1, wherein the dose of the compound of Formula (I) or a pharmaceutical acceptable salt thereof is about 30% to 70% less than the dose of the compound of Formula (I) or a pharmaceutical acceptable salt thereof that would otherwise have been recommended to the patient if the patient were not currently taking the cytochrome P450 inhibitor.

14. The method of claim 1, wherein the dose of the compound of Formula (I) or a pharmaceutical acceptable salt thereof is about 33% less than the dose of the compound of Formula (I) or a pharmaceutical acceptable salt thereof that would otherwise have been recommended to the patient if the patient were not currently taking the cytochrome P450 inhibitor.

15. The method of claim 1, wherein the dose of the compound of Formula (I) or a pharmaceutical acceptable salt thereof is about 66% less than the dose of the compound of Formula (I) or a pharmaceutical acceptable salt thereof that would otherwise have been recommended to the patient if the patient were not currently taking the cytochrome P450 inhibitor.

16. The method of claim 1, wherein a tartrate salt of the compound of Formula (I) is administered to the patient.

17. The method of claim 16, wherein the tartrate salt of the compound of Formula (I) in a dose of less than 32 mg is administered to the patient.

18. The method of claim 16, wherein the tartrate salt of the compound of Formula (I) in a dose of less than 27 mg is administered to the patient.

19. The method of claim 16, wherein the tartrate salt of the compound of Formula (I) in a dose of less than 18 mg is administered to the patient.

20. The method of claim 16, wherein the tartrate salt of the compound of Formula (I) in a dose of less than 14 mg is administered to the patient.

21. The method of claim 16, wherein the tartrate salt of the compound of Formula (I) in a dose of less than 12 mg is administered to the patient.

22. The method of claim 16, wherein the tartrate salt of the compound of Formula (I) in a dose of about 10-24 mg is administered to the patient.

23. The method of claim 16, wherein the tartrate salt of the compound of Formula (I) in a dose of about 20 mg is administered to the patient.

24. The method of claim 1, wherein the tartrate salt of the compound of Formula (I) is administered daily.

25. The method of claim 24, wherein the tartrate salt of compound of (I) is administered once daily.

26. The method of claim 1, wherein the tartrate salt of compound of Formula (I) is formulated for oral administration as a unit dose.

27. The method of claim 26, wherein the unit dose is a tablet.

28. The method of claim 1, wherein the tartrate salt of the compound of Formula (I) is in a crystalline form, wherein the crystalline form of the tartrate salt of the compound of Formula (I) exhibits a X-ray powder diffraction pattern comprising peaks having d-values in angstroms (Å

) of about 10.7, about 4.84, about 4.57, and about 3.77.

29. The method of claim 1, wherein the dose of the compound of Formula (I) or a pharmaceutical acceptable salt thereof that would otherwise have been recommended to the patient if the patient were not currently taking the cytochrome P450 inhibitor is a manufacturer'"'"'s recommended dose in the absence of concomitant administration of the cytochrome P450 inhibitor.

30. A method for treating a disease or disorder in a patient who is currently taking a first dose of a compound of Formula (I) or a pharmaceutical acceptable salt thereof:

31-32. -32. (canceled)

33. A method of treating hallucinations or delusions associated with Parkinson'"'"'s disease psychosis in a patient who is taking a CYP3A4 inhibitor, the method comprising administering 10-24 mg daily of pimavanserin tartrate to the patient.