Methods of treating iga nephropathy with atrasentan

Abstract

Provided herein are methods of treating IgA nephropathy, comprising administering a therapeutically effective amount of atrasentan, or a pharmaceutically acceptable salt thereof, to a subject in need thereof. Also provided herein are methods of decreasing renal inflammation and/or fibrosis, decreasing the occurrence of hematuria, stabilizing eGFR, decreasing the number of IgA-nephropathy associated disease flares, delaying the onset of ESRD, decreasing proteinuria, and decreasing fatigue in a subject having IgA nephropathy, comprising administering a therapeutically effective amount of atrasentan, or a pharmaceutically acceptable salt thereof, to the subject. In some embodiments, the subject has not been previously diagnosed with one or more of diabetic nephropathy, HIV/AIDS, HIV-related nephropathy, prostate cancer, or acute kidney failure.

1 - 44 . (canceled) 
     
     
         45 . A method of treating IgA nephropathy, comprising administering a therapeutically effective amount of atrasentan, or a pharmaceutically acceptable salt thereof, to a subject in need thereof;
 wherein the subject does not have one or more of diabetic nephropathy, HIV/AIDS, or acute kidney failure.   
     
     
         46 . The method of  claim 45 , wherein the atrasentan is administered as a pharmaceutically acceptable salt. 
     
     
         47 . The method of  claim 46 , wherein the atrasentan is administered as atrasentan hydrochloride or atrasentan mandelate. 
     
     
         48 . The method of  claim 45 , wherein the atrasentan is administered as atrasentan hydrochloride. 
     
     
         49 . The method of  claim 45 , wherein the atrasentan is administered as atrasentan mandelate. 
     
     
         50 . The method of  claim 45 , wherein the atrasentan is administered as the free base. 
     
     
         51 . The method of  claim 45 , wherein the therapeutically effective amount of atrasentan, or a pharmaceutically acceptable salt thereof, is from about 0.20 mg to about 1.5 mg of atrasentan, or an equivalent amount of a pharmaceutically acceptable salt thereof. 
     
     
         52 . The method of  claim 51 , wherein the therapeutically effective amount of atrasentan, or a pharmaceutically acceptable salt thereof, is from about 0.25 mg to about 1.25 mg of atrasentan, or an equivalent amount of a pharmaceutically acceptable salt thereof. 
     
     
         53 . The method of  claim 52 , wherein the therapeutically effective amount of atrasentan, or a pharmaceutically acceptable salt thereof, is from about 0.40 mg to about 0.85 mg of atrasentan, or an equivalent amount of a pharmaceutically acceptable salt thereof. 
     
     
         54 . The method of  claim 53 , wherein the therapeutically effective amount of atrasentan, or a pharmaceutically acceptable salt thereof, is about 0.75 mg of atrasentan, or an equivalent amount of a pharmaceutically acceptable salt thereof. 
     
     
         55 . The method of  claim 45 , wherein the subject is concomitantly receiving an ACE inhibitor, an ARB, or a combination thereof. 
     
     
         56 . The method of  claim 55 , wherein the ACE inhibitor is selected from: quinapril, fosinopril, perindopril, captopril, enalapril, enalaprilat, ramipril, cilazapril, delapril, fosenopril, zofenopril, indolapril, benazepril, lisinopril, spirapril, trandolapril, perindep, pentopril, moexipril, rescinnamine, and pivopril. 
     
     
         57 . The method of  claim 56 , wherein the ACE inhibitor is selected from: quinapril, fosinopril, captopril, enalapril, and lisinopril. 
     
     
         58 . The method of  claim 55 , wherein the ARB is selected from: candesartan, candesartan cilexetil, eprosartan, irbesartan, losartan, olmesartan, olmesartan medoxomil, telmisartan, valsartan, azilsartan medoxomil, and BRA-657. 
     
     
         59 . The method of  claim 58 , wherein the ARB is selected from: candesartan, losartan, olmesartan, and valsartan. 
     
     
         60 . The method of  claim 45 , further comprising administering a therapeutically effective amount of a SGLT-2 inhibitor. 
     
     
         61 . The method of  claim 60 , wherein the SGLT-2 inhibitor is selected from dapagliflozin, canagliflozin, ipragliflozin, empaglifozin, bexagliflozin, licogliflozin, janagliflozin (XZP-5695), tofogliflozin, ertugliflozin, henagliflozin (SHR-3824), enavogliflozin (DWP-16001), TA-1887 (3-(4-cyclopropylbenzyl)-4-fluoro-1-(β-D-glucopyranosyl)-1H-indole), indole-N-glycoside 18 (3-(4-ethylbenzyl)-1-(β-D-glucopyranosyl)-1H-indole), sotagliflozin, luseogliflozin, sergliflozin etabonate, remogliflozin, remogliflozin etabonate, and T-1095 (((2R,3 S,4S,5R,6S)-6-(2-(3-(benzofuran-5-yl)propanoyl)-3-hydroxy-5-methylphenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl) etabonate). 
     
     
         62 . The method of  claim 61 , wherein the SGLT-2 inhibitor is selected from bexagliflozin, canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, ipragliflozin, luseogliflozin, remogliflozin, serfliflozin, licofliglozin, sotagliflozin, and tofogliflozin. 
     
     
         63 . The method of  claim 62 , wherein the SGLT-2 inhibitor is canagliflozin, dapagliflozin, empagliflozin, or ertugliflozin. 
     
     
         64 . The method of  claim 45 , wherein the subject is administered a SGLT-2 inhibitor and one or more ACE inhibitors and/or one or more ARBs. 
     
     
         65 . The method of  claim 45 , wherein the subject is administered a SGLT-2 inhibitor and one or more ACE inhibitors. 
     
     
         66 . The method of  claim 65 , wherein the subject is administered a SGLT-2 inhibitor and an ACE inhibitor. 
     
     
         67 . The method of  claim 45 , wherein the subject is administered a SGLT-2 inhibitor and one or more ARBs. 
     
     
         68 . The method of  claim 67 , wherein the subject is administered a SGLT-2 inhibitor and an ARB. 
     
     
         69 . The method of  claim 45 , wherein the subject is excreting an average of about 0.5 grams or more of protein in the urine per day prior to the first administration of atrasentan, or a pharmaceutically acceptable salt thereof. 
     
     
         70 . The method of  claim 69 , wherein the subject is excreting an average of about 0.75 grams or more of protein in the urine per day prior to the first administration of atrasentan, or a pharmaceutically acceptable salt thereof. 
     
     
         71 . The method of  claim 70 , wherein the subject is excreting an average of about 1 gram or more of protein in the urine per day prior to the first administration of atrasentan, or a pharmaceutically acceptable salt thereof. 
     
     
         72 . The method of  claim 45 , wherein the subject has an average eGFR of about 20 mL/min/1.73 m 2  or above prior to the first administration of atrasentan, or a pharmaceutically acceptable salt thereof. 
     
     
         73 . The method of  claim 45 , wherein the subject has an average eGFR of about 20 to about 90 mL/min/1.73 m 2  prior to the first administration of atrasentan, or a pharmaceutically acceptable salt thereof. 
     
     
         74 . The method of  claim 45 , wherein the subject has an average eGFR of about 30 to about 60 mL/min/1.73 m 2  prior to the first administration of atrasentan, or a pharmaceutically acceptable salt thereof.