Combination of zibotentan and dapagliflozin for the treatment of endothelin related diseases
The present disclosure relates to the endothelin receptor antagonist (ERA) zibotentan in combination with the sodium-dependent glucose cotransporter 2 (SGLT-2) inhibitor dapagliflozin for use in the treatment of certain endothelin related diseases.
1. A method of treating chronic kidney disease in a human patient, the method comprising administering to the patient in need thereof, a combination of zibotentan, N-(3-methoxy-5-methylpyrazin-2-yl)-2-[4-(1,3,4-oxadiazol-2-yl)phenyl]pyridine-3-sulfonamide,
or a pharmaceutically acceptable salt thereof, and dapagliflozin.
2. The method according to claim 1 , where zibotentan, or a pharmaceutically acceptable salt thereof, is administered once daily in combination with dapagliflozin.
3. The method according to claim 2 , where zibotentan, or a pharmaceutically acceptable salt thereof, is administered once daily at a dose of about 5 mg in combination with dapagliflozin administered at a dose of 10 mg.
4. The method according to claim 2 , where zibotentan, or a pharmaceutically acceptable salt thereof, is administered once daily at a dose of about 1.5 mg in combination with dapagliflozin administered at a dose of 10 mg.
5. The method according to claim 2 , where zibotentan, or a pharmaceutically acceptable salt thereof, is administered once daily at a dose of about 0.25 mg in combination with dapagliflozin administered at a dose of 10 mg.
6. The method according to claim 2 , wherein the patient is a Chronic Kidney Disease patient classified as a stage 1-4 patient having an eGFR 20-60 ml/min/1.73 m2.
7. The method according to claim 6 , wherein the human patient is a Chronic Kidney Disease patient classified as a stage 3-4 patient.
8. A method of reducing the risk of eGFR decline in a human patient with chronic kidney disease, the method comprising administering to the patient in need thereof, a combination of zibotentan, N-(3-methoxy-5-methylpyrazin-2-yl)-2-[4-(1,3,4-oxadiazol-2-yl)phenyl]pyridine-3-sulfonamide,
or a pharmaceutically acceptable salt thereof, and dapagliflozin.
9. The method according to claim 8 , where zibotentan, or a pharmaceutically acceptable salt thereof, is administered once daily in combination with dapagliflozin.
10. The method according to claim 8 , where zibotentan, or a pharmaceutically acceptable salt thereof, is administered once daily at a dose of about 5 mg in combination with dapagliflozin administered at a dose of 10 mg.
11. The method according to claim 8 , where zibotentan, or a pharmaceutically acceptable salt thereof, is administered once daily at a dose of about 1.5 mg in combination with dapagliflozin administered at a dose of 10 mg.
12. The method according to claim 8 , where zibotentan, or a pharmaceutically acceptable salt thereof, is administered once daily at a dose of about 0.25 mg in combination with dapagliflozin administered at a dose of 10 mg.
13. The method according to claim 8 , wherein the patient is a Chronic Kidney Disease patient classified as a stage 1-4 patient having an eGFR 20-60 ml/min/1.73 m2.
14. The method according to claim 13 , wherein the human patient is a Chronic Kidney Disease patient classified as a stage 3-4 patient.
15. A method of reducing the risk of fluid retention decline in a human patient with chronic kidney disease, the method comprising administering to the patient in need thereof, a combination of zibotentan, N-(3-methoxy-5-methylpyrazin-2-yl)-2-[4-(1,3,4-oxadiazol-2-yl)phenyl]pyridine-3-sulfonamide,
or a pharmaceutically acceptable salt thereof, and dapagliflozin.
16. The method according to claim 15 , where zibotentan, or a pharmaceutically acceptable salt thereof, is administered once daily in combination with dapagliflozin.
17. The method according to claim 15 , where zibotentan, or a pharmaceutically acceptable salt thereof, is administered once daily at a dose of about 5 mg in combination with dapagliflozin administered at a dose of 10 mg.
18. The method according to claim 15 , where zibotentan, or a pharmaceutically acceptable salt thereof, is administered once daily at a dose of about 1.5 mg in combination with dapagliflozin administered at a dose of 10 mg.
19. The method according to claim 15 , where zibotentan, or a pharmaceutically acceptable salt thereof, is administered once daily at a dose of about 0.25 mg in combination with dapagliflozin administered at a dose of 10 mg.
20. The method according to claim 15 , wherein the patient is a Chronic Kidney Disease patient classified as a stage 1-4 patient having an eGFR 20-60 ml/min/1.73 m2.
21. The method according to claim 20 , wherein the human patient is a Chronic Kidney Disease patient classified as a stage 3-4 patient.