COMBINATION OF A 17-ALPHA-HYDROXYLASE (C17,20-LYASE) INHIBITOR AND A SPECIFIC PI-3K INHIBITOR FOR TREATING A TUMOR DISEASE

• US 20150157645A1
• Filed: 06/04/2013
• Published: 06/11/2015
• Est. Priority Date: 06/06/2012
• Status: Abandoned Application

• Current Assignee: Novartis Ag
• Original Assignee: Novartis Ag
• Inventors: Hirawat, Samit, Riva, Alessandro, Prakash, Mistry
• Application Number:
  US14/404,957
• Publication Number:
  US 20150157645A1
• Time in Patent Office: Days
• US Class Current: 1/1
• 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 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/444 containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
• CPC Class Codes: A61K 31/4745 condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present invention relates to a combination which comprises (a) a phosphatidylinositol 3-kinase inhibitor selected from the group consisting of a compound of formula (I) or a compound of formula (II), or pharmaceutically acceptable salt thereof, (b) a 17α-Hydroxylase/C_17,20-lyase inhibitor (CYP17 inhibitor), specifically abiraterone acetate and 1-(2-Chloro-pyridin-4-yl)-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one or pharmaceutically acceptable salt thereof, for simultaneous, separate or sequential use for the treatment of a tumor disease; a pharmaceutical composition comprising such combination; use of such combination for the treatment of a tumor disease; a commercial package or product comprising such combination; and to a method of treating a patient having a tumor disease comprising administration of said combination to a patient in need thereof.

Claims

1. A combination comprising (a) a phosphatidylinositol 3-kinase inhibitor selected from the group consisting of the compound of formula (I),

2. A combination according to claim 1, wherein the phosphatidylinositol 3-kinase inhibitor is 2-methyl-2-[4-(3-methyl-2-oxo-8-quinolin-3-yl-2,3-dihydro-imidazo[4,5-c]quinolin-1-yl)-phenyl]-propionitrile (COMPOUND A), 8-(6-methoxy-pyridin-3-yl)-3-methyl-1-(4-piperazin-1-yl-3-trifluoromethyl-phenyl)-1,3-dihydro-imidazo[4,5-c]quinolin-2-one (COMPOUND B) or a pharmaceutically acceptable salt thereof.

3. A combination according to claim 1, wherein the phosphatidylinositol 3-kinase inhibitor is 5-(2,6-di-morpholin-4-yl-pyrimidin-4-yl)-4-trifluoromethyl-pyridin-2-ylamine (COMPOUND C) or a pharmaceutically acceptable salt thereof.

4. A combination according to claim 1 wherein the 17α

-Hydroxylase/C_17,20-lyase inhibitor is selected from the group consisting of ketoconazole, abiraterone acetate, abiraterone, 1-(2-Chloro-pyridin-4-yl)-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one or a pharmaceutically acceptable salt thereof.

7. A combination according to claim 1 further comprising at least one additional therapeutic agent.

8. A combination according to claim 7 wherein the at least one additional therapeutic agent is a steroid selected from the group consisting of hydrocortisone, dexamethasone, prednisolone, prednisone and combinations thereof, and any pharmaceutically acceptable salt thereof.

9. A pharmaceutical composition comprising a combination according to any one of claims 1 to 4 and at least one pharmaceutically acceptable carrier.

5-6. -6. (canceled)

10. A method of treating a patient having a tumor disease which comprises administering to a subject in need thereof a combination comprising a phosphatidylinositol 3-kinase inhibitor selected from the group consisting of 2-methyl-2-[4-(3-methyl-2-oxo-8-quinolin-3-yl-2,3-dihydro-imidazo[4,5-c]quinolin-1-yl)-phenyl]-propionitrile (COMPOUND A), 8-(6-methoxy-pyridin-3-yl)-3-methyl-1-(4-piperazin-1-yl-3-trifluoromethyl-phenyl)-1,3-dihydro-imidazo[4,5-c]quinolin-2-one (COMPOUND B), and 5-(2,6-di-morpholin-4-yl-pyrimidin-4-vl)-4-trifluoromethyl-pyridin-2-ylamine (COMPOUND C) or a pharmaceutically acceptable salt thereof and (b) a 17α

-Hydroxylase/C_17,20-lyase inhibitor or pharmaceutically acceptable salt thereof in a quantity which is jointly therapeutically effective against said tumor disease.

12. A method according to claim 10, wherein the tumor disease is prostate.

14. A method according to claim 10, wherein the amount of (a) and the amount of (b) are in a single formulation or unit dosage form.

15. A method according to claim 10, wherein the amount of (a) and the amount of (b) are in a separate formulations or unit dosage forms.

16. A method according to claim 10 which further comprises administering to a patient in need thereof a combination according to claim 10 in combination with at least one additional therapeutic agent.

18. A method according to claim 16 wherein the additional therapeutic agent is a steroid selected from the group consisting of hydrocortisone, dexamethasone, prednisolone, prednisone and combinations thereof, and any pharmaceutically acceptable salt thereof.

20. A method according to claim 10, wherein the tumor disease is selected from the group consisting of benign or malignant tumors, carcinoma of the brain, kidney, liver, bladder, breast, gastric, ovaries, colon, rectum, prostate, pancreas, lung, vagina or thyroid, or gastrointestinal cancers.

11. (canceled)

13. (canceled)

17. (canceled)

19. (canceled)