Claims for Patent: 11,787,820

Summary for Patent: 11,787,820

Title:	Method of treating certain sex hormone-dependent diseases administering a soft gelatin capsule comprising NK1 and NK3 receptors antagonists
Abstract:	The present invention generally relates to novel pharmaceutical formulations containing 2-[3,5-Bis(trifluoromethyl)phenyl]-N-{4-(4-fluoro-2-methylphenyl)-6-[(7S,9aS)-7-(hydroxymethyl)hexahydropyrazino[2,1-c][1,4]oxazin-8(1H)-yl]-3-pyridinyl}-N,2-dimethylpropanamide, methods of preparation thereof and their use in medical therapy.
Inventor(s):	Mike Trower, Monica Lazaro, Derek BUSH, David Elder, Mary Kerr
Assignee:	Kandy Therapeutics Ltd
Application Number:	US16/985,087
Patent Claims:	1. A method of treating sex hormone-dependent diseases selected from vasomotor symptoms (VMS), endometriosis, uterine fibroid tumor, heavy menstrual bleeding, or polycystic ovary syndrome (PCOS) comprising administering to a human in need thereof one or more soft gelatin capsule comprising: (a) Compound A or a pharmaceutically acceptable salt thereof; (b) at least one solubilizer selected from caprylocaproyl polyoxyl-8 glycerides, glycerol monocaprylocaprate, polyoxyl 35 castor oil, polysorbate 80, or mixtures thereof; and (c) at least one antioxidant selected from dl-alpha-tocopherol, butylated hydroxytoluene, butylated hydroxyanisole or mixtures thereof. 2. The method of claim 1, wherein Compound A is in a crystalline anhydrate form. 3. The method of claim 1, wherein Compound A is in crystalline anhydrate Form 1, characterized by X-ray powder diffraction (XRD) pattern expressed in terms of 2 theta angles, wherein the XRD pattern comprises 2 theta angle peaks at 4.3±0.1, 7.9±0.1, 9.8±0.1, 10.7±0.1, 10.8±0.1, 13.3±0.1, 14.0±0.1, 15.1±0.1 degrees, which correspond respectively to d-spacing at 20.4, 11.1, 9.0, 8.3, 8.2, 6.6, 6.3 and 5.9 Angstroms (Å). 4. The method of claim 1, wherein the sex hormone-dependent disease is vasomotor symptoms (VMS). 5. The method of claim 1, wherein the sex hormone-dependent disease is endometriosis. 6. The method of claim 1, wherein the sex hormone-dependent disease is uterine fibroid tumor. 7. The method of claim 1, wherein the sex hormone-dependent disease is heavy menstrual bleeding. 8. The method of claim 1, wherein the sex hormone-dependent disease is polycystic ovary syndrome (PCOS). 9. The method of claim 1, wherein each soft gelatin capsule further comprises one or more additional therapeutic agents. 10. The method of claim 1, wherein each soft gelatin capsule further comprises (d) at least one emulsifier selected from glyceryl monooleate, Miglyol 812, or a mixture thereof. 11. The method of claim 1, wherein each soft gelatin capsule comprises Compound A in an amount from 10 mg to 80 mg. 12. The method of claim 10, wherein each soft gelatin capsule comprises Compound A in an amount from 10 mg to 80 mg. 13. The method of claim 1, wherein each soft gelatin capsule comprises Compound A at a concentration ranging from 0.8% w/w to 15% w/w or from 5% w/w to 10% w/w. 14. The method of claim 10, wherein each soft gelatin capsule comprises Compound A at a concentration ranging from 0.8% w/w to 15% w/w or from 5% w/w to 10% w/w. 15. The method of claim 1, wherein each soft gelatin capsule comprises at least one solubilizer selected from glycerol monocaprylocaprate, caprylocaproyl polyoxyl-8 glycerides, or polysorbate 80. 16. The method of claim 10, wherein each soft gelatin capsule comprises at least one solubilizer selected from glycerol monocaprylocaprate, caprylocaproyl polyoxyl-8 glycerides, or polysorbate 80. 17. The method of claim 10, wherein the at least one emulsifier present in each soft gelatin capsule is glyceryl monooleate. 18. The method of claim 1, wherein at least one antioxidant present in each soft gelatin capsule is dl-alpha-tocopherol. 19. The method of claim 10, wherein at least one antioxidant present in each soft gelatin capsule is dl-alpha-tocopherol. 20. The method of claim 1, wherein the soft gelatin capsule comprises: (a) Compound A; (b1) glycerol monocaprylocaprate; (b2) caprylocaproyl polyoxyl-8-glycerides; (b3) polysorbate 80; and (c) dl-alpha-tocopherol. 21. The method of claim 1, wherein each soft gelatin capsule comprises: (a) Compound A; (b1) glycerol monocaprylocaprate; (b2) caprylocaproyl polyoxyl-8-glycerides; (b3) polysorbate 80; (c) dl-alpha-tocopherol; and (d) glyceryl monooleate. 22. The method of claim 15, wherein glycerol monocaprylocaprate is present in each soft gelatin capsule at a concentration ranging from 20% w/w to 65% w/w. 23. The method of claim 16, wherein glycerol monocaprylocaprate is present in each soft gelatin capsule at a concentration ranging from 20% w/w to 65% w/w. 24. The method of claim 15, wherein caprylocaproyl polyoxyl-8 glycerides is present in each soft gelatin capsule at a concentration ranging from 7% w/w to 13% w/w. 25. The method of claim 16, wherein caprylocaproyl polyoxyl-8 glycerides is present in each soft gelatin capsule at a concentration ranging from 7% w/w to 13% w/w. 26. The method of claim 15, wherein polysorbate 80 is present in each soft gelatin capsule at a concentration from 7% w/w to 13% w/w. 27. The method of claim 16, wherein polysorbate 80 is present in each soft gelatin capsule at a concentration from 7% w/w to 13% w/w. 28. The method of claim 17, wherein glyceryl monooleate is present in each soft gelatin capsule at a concentration ranging from 15% w/w to 60% w/w. 29. The method of claim 18, wherein dl-alpha-tocopherol is present in each soft gelatin capsule at a concentration ranging from 0.05% w/w to 1.5% w/w. 30. The method of claim 19, wherein dl-alpha-tocopherol is present in each soft gelatin capsule at a concentration ranging from 0.05% w/w to 1.5% w/w. 31. A method of treating sex hormone-dependent diseases selected from vasomotor symptoms (VMS), endometriosis, uterine fibroid tumor, heavy menstrual bleeding, or polycystic ovary syndrome (PCOS) comprising administering to a human in need thereof one or more soft gelatin capsule comprising: (a) Compound A present at a concentration ranging from 5% w/w to 10% w/w; (b1) glycerol monocaprylocaprate present at a concentration ranging from 20% w/w to 65% w/w; (b2) caprylocaproyl polyoxyl-8 glycerides present at a concentration ranging from 7% w/w to 13% w/w; (b3) polysorbate 80 present at a concentration from 7% w/w to 13% w/w; (c) dl-alpha-tocopherol present at a concentration ranging from 0.5% w/w to 1% w/w; and (d) glyceryl monooleate. 32. The method of claim 31, wherein each soft gel capsule is prepared by a method comprising adding Compound A to a mixture comprising 15% w/w to 60% w/w glyceryl monooleate, glycerol monocaprylocaprate, caprylocaproyl polyoxyl-8 glycerides, polysorbate 80, or dl-alpha-tocopherol, or any combination thereof. 33. The method of claim 31, wherein the glyceryl monooleate is present in each soft gelatin capsule at a concentration ranging from 15% w/w to 60% w/w. 34. A method of treating sex hormone-dependent diseases selected from vasomotor symptoms (VMS), endometriosis, uterine fibroid tumor, heavy menstrual bleeding, or polycystic ovary syndrome (PCOS) comprising administering to a human in need thereof one or more soft gelatin capsule comprising: (b) Compound A present at a concentration ranging from 1% w/w to 10% w/w; (b1) glycerol monocaprylocaprate present at a concentration ranging from 30% w/w to 40% w/w; (b2) caprylocaproyl polyoxyl-8 glycerides present at a concentration ranging from 7% w/w to 13% w/w; (b3) polysorbate 80 present at a concentration from 7% w/w to 13% w/w; (c) dl-alpha-tocopherol present at a concentration ranging from 0.5% w/w to 1% w/w; and (d) glyceryl monooleate. 35. The method of claim 34, wherein each soft gel capsule is prepared by a method comprising adding Compound A to a mixture comprising 33% w/w to 43% w/w glyceryl monooleate, glycerol monocaprylocaprate, caprylocaproyl polyoxyl-8 glycerides, polysorbate 80, or dl-alpha-tocopherol, or any combination thereof. 36. The method of claim 34, wherein the glyceryl monooleate is present in each soft gelatin capsule at a concentration ranging from 33% w/w to 43% w/w. 37. The method of claim 1, wherein one soft gelatin capsule is administered to the human, and the soft gelatin capsule comprises Compound A in an amount from 1 mg to 250 mg. 38. The method of claim 10, wherein one soft gelatin capsule is administered to the human, and the soft gelatin capsule comprises Compound A in an amount from 1 mg to 250 mg. 39. The method of claim 4, wherein Compound A is administered at a daily dose of 100 mg to 160 mg. 40. The method according to claim 39, wherein Compound A is administered at a daily dose of 120 mg. 41. The method according to claim 40, wherein two soft gelatin capsules are administered, and each soft gelatin capsule comprises Compound A in an amount of 60 mg.