Claims for Patent: 12,551,447

Summary for Patent: 12,551,447

Title:	Combination solid oral dosage forms of gonadotropin-releasing hormone antagonists
Abstract:	The present disclosure includes combination solid oral dosage forms having 40 mg of N-(4-(1-(2,6-difluorobenzyl)-5-((dimethylamino)methyl)-3-(6-methoxy-3-pyridazinyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-N′-methoxyurea, or a corresponding amount of a pharmaceutically acceptable salt thereof, and hormone replacement medicaments. Also provided are processes for making and using the solid oral dosage forms.
Inventor(s):	David E. ALONZO, Kathleen D. ULLMER, Minli Xie
Assignee:	Sumitomo Pharma Co Ltd
Application Number:	US18/070,341
Patent Claims:	1. A combination solid oral dosage form comprising: about 18% to 22% w/w of N-(4-(1-(2,6-difluorobenzyl)-5-((dimethylamino)methyl)-3-(6-methoxy-3-pyridazinyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-N′-methoxyurea, or a corresponding amount of a pharmaceutically acceptable salt thereof; about 0.3% to 0.7% w/w of estradiol; about 0.1% to 0.4% w/w of norethindrone acetate; about 24% to 28% w/w of mannitol; about 2% to 6% w/w of a starch selected from the group consisting of sodium starch glycolate, pregelatinized starch, and a combination of the foregoing; about 0.5% to 3% w/w of hydroxypropyl cellulose; about 0.5% to 3% w/w of magnesium stearate; about 38% to 42% w/w of lactose monohydrate; and about 1% to 5% w/w of a film coating. 2. The combination solid oral dosage form of claim 1 comprising: about 40 mg of N-(4-(1-(2,6-difluorobenzyl)-5-((dimethylamino)methyl)-3-(6-methoxy-3-pyridazinyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-N′-methoxyurea, or a corresponding amount of a pharmaceutically acceptable salt thereof; about 1 mg of estradiol; about 0.5 mg of norethindrone acetate; about 51 mg of mannitol; about 9 mg of sodium starch glycolate; about 3 mg of hydroxypropyl cellulose; about 2 mg of magnesium stearate; about 78 mg of lactose monohydrate; and about 7 mg of a film coating. 3. The combination solid oral dosage form of claim 1, wherein the starch is sodium starch glycolate. 4. The combination solid oral dosage form of claim 3, wherein the combination solid oral dosage form comprises about 9 mg of sodium starch glycolate. 5. The combination solid oral dosage form of claim 1, wherein the starch is pregelatinized starch. 6. The combination solid oral dosage form of claim 1, wherein the starch is a combination of sodium starch glycolate and pregelatinized starch. 7. The combination solid oral dosage form of claim 6 comprising about 2% to 3% w/w sodium starch glycolate and about 2% to 3% w/w pregelatinized starch. 8. The combination solid oral dosage form of claim 1, wherein the amount of relugolix degradant present after storing said combination solid oral dosage form for 6 months, at 60° C. and ambient relative humidity, does not exceed 0.5% w/w. 9. The combination solid oral dosage form of claim 1, wherein the amount of estradiol degradant present after storing said combination solid oral dosage form for 6 months, at 60° C. and ambient relative humidity, does not exceed 1.4% w/w. 10. The combination solid oral dosage form of claim 1, wherein the amount of norethindrone acetate degradant present after storing said combination solid oral dosage form for 6 months, at 60° C. and ambient relative humidity, does not exceed 1.4% w/w. 11. The combination solid oral dosage form of claim 1, wherein when administered orally to a subject the mean maximum plasma concentration (Cmax) of N-(4-(1-(2,6-difluorobenzyl)-5-((dimethylamino)methyl)-3-(6-methoxy-3-pyridazinyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-N′-methoxyurea, or a corresponding amount of a pharmaceutically acceptable salt thereof, is in the range of 10 ng/ml to 30 ng/mL. 12. The combination solid oral dosage form of claim 2, wherein when administered orally to a subject the mean maximum plasma concentration (Cmax) of N-(4-(1-(2,6-difluorobenzyl)-5-((dimethylamino)methyl)-3-(6-methoxy-3-pyridazinyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-N′-methoxyurea, or a corresponding amount of a pharmaceutically acceptable salt thereof, is in the range of 10 ng/ml to 30 ng/mL.