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 - 9 . (canceled)
10 . A method of reducing total body water in a human patient with chronic kidney disease and in need thereof, the method comprising administering to the patient 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 in amounts effective for reducing total body water in the patient.
11 . The method of claim 10 , wherein zibotentan or a pharmaceutically acceptable salt thereof is administered once daily in combination with dapagliflozin.
12 . The method of claim 11 , wherein zibotentan or a pharmaceutically acceptable salt thereof is administered at a dose of about 5 mg and dapagliflozin is administered at a dose of 10 mg.
13 . The method of claim 11 , wherein zibotentan or a pharmaceutically acceptable salt thereof is administered at a dose of about 1.5 mg and dapagliflozin is administered at a dose of 10 mg.
14 . The method of claim 11 , wherein zibotentan or a pharmaceutically acceptable salt thereof is administered at a dose of about 0.25 mg and dapagliflozin is administered at a dose of 10 mg.
15 . The method of claim 11 , wherein the patient is a chronic kidney disease patient classified as a stage 1-4 patient having an eGFR of 20-60 ml/min/1.73 m 2 .
16 . The method of claim 15 , wherein the patient is a chronic kidney disease patient classified as a stage 3-4 patient.
17 . A method of reducing risk of fluid retention in a human patient with chronic kidney disease and in need thereof, the method comprising administering to the patient 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 in amounts effective for reducing total body water in the patient.
18 . The method of claim 17 , wherein zibotentan or a pharmaceutically acceptable salt thereof is administered once daily in combination with dapagliflozin.
19 . The method of claim 18 , wherein zibotentan or a pharmaceutically acceptable salt thereof is administered at a dose of about 5 mg and dapagliflozin is administered at a dose of 10 mg.
20 . The method of claim 18 , wherein zibotentan or a pharmaceutically acceptable salt thereof is administered at a dose of about 1.5 mg and dapagliflozin is administered at a dose of 10 mg.
21 . The method of claim 18 , wherein zibotentan or a pharmaceutically acceptable salt thereof is administered at a dose of about 0.25 mg and dapagliflozin is administered at a dose of 10 mg.
22 . The method of claim 18 , wherein the patient is a chronic kidney disease patient classified as a stage 1-4 patient having an eGFR of 20-60 ml/min/1.73 m 2 .
23 . The method of claim 22 , wherein the patient is a chronic kidney disease patient classified as a stage 3-4 patient.
24 . A method of reducing the likelihood of cardiovascular death in a human patient with chronic kidney disease and in need thereof, the method comprising administering to the patient, 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 in amounts effective for reducing the incidence of cardiovascular or renal death in the patient.
25 . The method of claim 24 , wherein zibotentan or a pharmaceutically acceptable salt thereof is administered once daily in combination with dapagliflozin.
26 . The method of claim 25 , wherein zibotentan or a pharmaceutically acceptable salt thereof is administered at a dose of about 5 mg and dapagliflozin is administered at a dose of 10 mg.
27 . The method of claim 25 , wherein zibotentan or a pharmaceutically acceptable salt thereof is administered at a dose of about 1.5 mg and dapagliflozin is administered at a dose of 10 mg.
28 . The method of claim 25 , wherein zibotentan or a pharmaceutically acceptable salt thereof is administered at a dose of about 0.25 mg and dapagliflozin is administered at a dose of 10 mg.
29 . The method of claim 25 , wherein the patient is a chronic kidney disease patient classified as a stage 1-4 patient having an eGFR of 20-60 ml/min/1.73 m 2 .
30 . The method of claim 29 , wherein the patient is a chronic kidney disease patient classified as a stage 3-4 patient.