Atrasentan mandelate salts

Abstract

The present disclosure relates to: (a) mandelate salts of atrasentan, (b) pharmaceutical compositions comprising an atrasentan mandelate salt, and, optionally, one or more additional therapeutic agents; (b) methods of using an atrasentan mandelate salt to treat nephropathy, chronic kidney disease, and/or other conditions; (c) kits comprising a first pharmaceutical composition comprising an atrasentan mandelate salt, and, optionally, a second pharmaceutical composition comprising one or more additional therapeutic agents; (d) methods for the preparation of an atrasentan mandelate salt; and (e) atrasentan mandelate salts prepared by such method.

1 . A crystalline atrasentan S-mandelate solvated salt. 
     
     
         2 - 3 . (canceled) 
     
     
         4 . An amorphous atrasentan S-mandelate salt. 
     
     
         5 . The salt of  claim 1 , wherein the molar ratio of atrasentan to S-mandelate is about 1:1. 
     
     
         6 - 7 . (canceled) 
     
     
         8 . The salt of  claim 1 , wherein the solvated salt is selected from the group consisting of an acetonitrile solvate, an ethanol solvate, and a pyridine solvate. 
     
     
         9 - 13 . (canceled) 
     
     
         14 . An atrasentan R-mandelate salt. 
     
     
         15 . The salt of  claim 14 , wherein the salt is a crystalline R-mandelate salt. 
     
     
         16 . The salt of  claim 14 , wherein the salt is an amorphous R-mandelate salt. 
     
     
         17 . The salt of  claim 15 , wherein the molar ratio of atrasentan to R-mandelate is about 1:1. 
     
     
         18 . The salt of  claim 17 , wherein the salt is an anhydrous salt. 
     
     
         19 . The salt of  claim 18 , wherein the salt is a crystalline R-mandelate salt having an X-ray powder diffraction pattern comprising peaks at 5.7±0.2, 11.8±0.2, and 20.9±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation. 
     
     
         20 . A pharmaceutical composition comprising an atrasentan mandelate salt and a pharmaceutically-acceptable carrier. 
     
     
         21 . The composition of  claim 20 , wherein the composition comprises from about 0.25 mg to about 1.25 mg of the salt on an atrasentan parent equivalent weight basis. 
     
     
         22 . The composition of  claim 20 , wherein the salt is a crystalline S-mandelate solvated salt. 
     
     
         23 . The composition of  claim 22 , wherein the molar ratio of atrasentan to S-mandelate is about 1:1. 
     
     
         24 . The composition of  claim 20 , wherein the salt is an R-mandelate salt. 
     
     
         25 . A method of treating chronic kidney disease, comprising administering a therapeutically effective amount of an atrasentan mandelate salt to a human subject susceptible to or suffering from chronic kidney disease. 
     
     
         26 . The method of  claim 25 , wherein the amount of the salt administered is from about 0.25 mg daily to about 1.25 mg daily on an atrasentan parent equivalent weight basis. 
     
     
         27 . A method of treating nephropathy, comprising administering a therapeutically effective amount of an atrasentan mandelate salt to a human subject susceptible to or suffering from nephropathy. 
     
     
         28 . The method of  claim 27 , wherein the amount of the salt administered is from about 0.25 mg daily to about 1.25 mg daily on an atrasentan parent equivalent weight basis. 
     
     
         29 . The method of  claim 27 , wherein the method reduces the urinary-albumin-to-creatinine ratio in the subject. 
     
     
         30 . The method of  claim 27 , wherein the method reduces the rate of increase in serum creatinine concentration in the subject. 
     
     
         31 . The composition of  claim 15 , wherein the salt is a hydrate. 
     
     
         32 . The composition of  claim 15 , wherein the salt is a solvated salt. 
     
     
         33 . The composition of  claim 32 , wherein the solvated salt is selected from the group consisting of an acetonitrile solvate, an ethanol solvate, and a pyridine solvate.