Methods for improving renal function with a combination of a bet bromodomain inhibitor and a sodium dependent glucose transport 2 inhibitor
Described herein are methods for treating and/or preventing a kidney disease or an associated disorder as measured by an increase in estimated glomerular filtration rate (eGFR) by administering to a subject in need thereof, a combination of a sodium-glucose transport protein 2 (SGLT2) inhibitor and a compound of Formula I or a stereoisomer, tautomer, pharmaceutically acceptable salt, or hydrate thereof, wherein the variables of Formula I are as defined herein.
1 . A method for treating a kidney disease or an associated disorder as measured by an increase in estimated glomerular filtration rate (eGFR), the method comprising administering to a subject in need thereof a combination of a sodium-glucose transport protein 2 (SGLT2) inhibitor and 2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one (RVX-208; RVX000222) or a pharmaceutically acceptable salt thereof, wherein the SGLT2 inhibitor is selected from empagliflozin, canagliflozin, and dapagliflozin.
2 . The method according to claim 1 , comprising administering to the subject a daily dose of 100-300 mg of 2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one (RVX-208; RVX000222) or an equivalent amount of a pharmaceutically acceptable salt thereof.
3 . The method according to claim 2 , comprising administering to the subject, a daily dose of 200 mg of 2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one (RVX-208; RVX000222) or an equivalent amount of a pharmaceutically acceptable salt thereof.
4 . The method according to claim 1 , wherein the 2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one (RVX-208; RVX000222) or pharmaceutically acceptable salt thereof is administered simultaneously with the SGLT2 inhibitor in separate compositions.
5 . The method according to claim 1 , wherein the 2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-5.7-dimethoxyquinazolin-4(3H)-one (RVX-208; RVX000222) or a pharmaceutically acceptable salt thereof is administered with the SGLT2 inhibitor in a single composition.
6 . The method according to claim 1 , wherein the subject is a human.
7 . The method according to claim 1 , wherein the subject is a human with type 2 diabetes or chronic kidney disease.
8 . The method according to claim 6 , wherein the subject is a human on statin therapy.
9 . The method according to claim 6 , wherein the subject is a human with low HDL cholesterol (below 40 mg/dL for males and below 45 mg/dl for females) and a recent acute coronary syndrome (ACS) (preceding 7-90 days).
10 . The method according to claim 1 , wherein the kidney disease or an associated disorder is a kidney disease associated with reduced eGFR.
11 . The method according to claim 10 , wherein the kidney disease associated with reduced eGFR is also associated with type 2 diabetes or a diabetes-related disease or disorder.
12 . The method according to claim 10 , wherein the kidney disease associated with reduced eGFR is nephropathy.
13 . The method according to claim 10 , wherein the kidney disease associated with reduced eGFR is diabetic nephropathy.
14 . The method according to claim 10 , wherein the kidney disease associated with reduced eGFR is chronic kidney disease.
15 . The method according to claim 10 , wherein the chronic kidney disease is a comorbidity of type 2 diabetes.
16 . The method according to claim 1 , wherein the treating comprises improving renal function by increasing eGFR slope.
17 . The method according to claim 1 , wherein the treating comprises reducing the decline of renal function by increasing eGFR slope.