Claims for Patent: 11,583,526

Summary for Patent: 11,583,526

Title:	Treatment of prostate cancer
Abstract:	Methods for treating prostate cancer, including advanced prostate cancer, in a subject in need thereof, include administering once-daily to the subject, at least 80 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. Another method includes: administering once-daily to the subject in need thereof, an oral load dose formulation having from 240 mg to 480 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 thereafter administering once-daily to the subject, an oral maintenance dose formulation having 80 mg to 160 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.
Inventor(s):	Vijaykumar Reddy RAJASEKHAR, Brendan Mark JOHNSON, David B. MacLean, Lynn Seely, Paul N. MUDD, Jr.
Assignee:	Sumitomo Pharma Switzerland GmbH , Takeda Pharmaceutical Co Ltd
Application Number:	US16/998,900
Patent Claims:	1. A method for treating advanced prostate cancer in a subject in need thereof, the method comprising: orally administering once daily to the subject 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; wherein on a first treatment day the subject is administered an oral loading dose of 360 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 wherein on all subsequent treatment days the subject is administered an oral maintenance dose of 120 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; wherein the oral loading dose provides a PK profile in which the subject's plasma AUC(0-24) 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 is greater than or equal to the subject's steady state AUC24 reached after administration of the oral maintenance doses. 2. The method according to claim 1, wherein steady state is reached within 10 days after the first treatment day. 3. A method of treating hormone dependent prostate cancer in a subject in need thereof, the method comprising: orally administering once-daily to the subject 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; wherein on a first treatment day the subject is administered an oral loading dose of 360 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 wherein on all subsequent treatment days the subject is administered an oral maintenance dose of 120 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]pyrimidin-6-yl)phenyl)-N′-methoxyurea, or a corresponding amount of a pharmaceutically acceptable salt thereof; wherein the oral load dose provides a PK profile in which the subject's plasma AUC(0-24) 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 is greater than or equal to the subject's steady state AUC24 reached after administration of the oral maintenance doses. 4. The method according to claim 3, wherein steady state is reached by the tenth treatment day. 5. The method of claim 1, wherein the subject's serum testosterone concentration is below 50 ng/dL by the eighth treatment day. 6. The method of claim 5, wherein the subject's serum testosterone concentration is below 50 ng/dL by the fourth treatment day. 7. The method of claim 6, wherein the subject's serum testosterone concentration is below 50 ng/dL within 24 to 48 hours after the first treatment day. 8. The method of claim 5, wherein the subject's serum testosterone concentration is below 20 ng/dL within five weeks after the first treatment day. 9. The method of claim 5, wherein the subject's serum testosterone concentration is below 20 ng/dL within three weeks after the first treatment day. 10. The method of claim 5, wherein the subject's serum testosterone concentration is below 20 ng/dL within two weeks after the first treatment day. 11. The method of claim 5, wherein the subject's serum testosterone concentration is below 20 ng/dL within one week after the first treatment day. 12. The method of claim 5, wherein the subject's serum testosterone concentration is below 20 ng/dL within 4 days after the first treatment day. 13. The method of claim 6, wherein the subject's serum testosterone concentration is below 20 ng/dL within five weeks after the first treatment day. 14. The method of claim 6, wherein the subject's serum testosterone concentration is below 20 ng/dL within three weeks after the first treatment day. 15. The method of claim 6, wherein the subject's serum testosterone concentration is below 20 ng/dL within two weeks after the first treatment day. 16. The method of claim 6, wherein the subject's serum testosterone concentration is below 20 ng/dL within one week after the first treatment day. 17. The method of claim 1, wherein the oral loading dose is administered as three, 120 mg doses 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. 18. The method of claim 3, wherein the oral loading dose is administered as three, 120 mg doses 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.