Biphenyl sulfonamide compounds for the treatment of kidney diseases or disorders

Abstract

Methods of treatment comprising administering a compound having structure (I), N O O2 S NH N N O O, (I) or a pharmaceutically acceptable salt thereof, or administering a pharmaceutical composition comprising the compound of structure (I) or pharmaceutically acceptable salt thereof, are provided.

What is claimed is: 
     
         1 . A pharmaceutical composition comprising a compound having structure (I), 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, for use in a method of treating a kidney disease or disorder in a subject in need thereof, the method comprising administering to said subject said pharmaceutical composition
 (i) in an amount sufficient to achieve a urine protein to creatinine (“UP/C”) ratio of less than or equal to 1.5 g/g; 
 (ii) in an amount sufficient to achieve or maintain a UP/C ratio of less than or equal to 1.5 g/g; or 
 (iii) at a dosing regimen sufficient to achieve or maintain a UP/C ratio of less than or equal to 1.5 g/g. 
 
     
     
         2 . The pharmaceutical composition for use according to  claim 1 , wherein the pharmaceutical composition is administered to said subject over an administration period in an amount sufficient to achieve or maintain a UP/C ratio of less than or equal to 1.5 g/g for at least a portion of said administration period. 
     
     
         3 . A pharmaceutical composition comprising a compound having structure (I), 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, for use in a therapeutic method of
 (i) maintaining a UP/C ratio at less than or equal to 1.5 g/g in a subject in need thereof, the method comprising administering to said subject said pharmaceutical composition in an amount sufficient to maintain a UP/C ratio of less than or equal to 1.5 g/g; or 
 (ii) reducing a UP/C ratio to less than or equal to 1.5 g/g in a subject in need thereof, the method comprising administering to said subject said pharmaceutical composition in an amount sufficient to reduce said patient's UP/C ratio to less than or equal to 1.5 g/g. 
 
     
     
         4 . The pharmaceutical composition for use according to any preceding claim, wherein said subject has, or has had, a UP/C ratio greater than 1.5 g/g prior to administration of said pharmaceutical composition. 
     
     
         5 . The pharmaceutical composition for use according to any preceding claim, wherein the method achieves a reduction in said subject's UP/C ratio of at least 40% relative to said subject's baseline UP/C ratio. 
     
     
         6 . The pharmaceutical composition for use according to any preceding claim, wherein a UP/C ratio of less than or equal to 1.5 g/g is achieved within 8 weeks of administering said pharmaceutical composition. 
     
     
         7 . The pharmaceutical composition for use according to any preceding claim, wherein a UP/C ratio of less than or equal to 1.5 g/g is achieved within 26 weeks of administering said pharmaceutical composition. 
     
     
         8 . The pharmaceutical composition for use according to any preceding claim, wherein a UP/C ratio of less than or equal to 1.5 g/g is achieved within 8 months of administering said pharmaceutical composition. 
     
     
         9 . The pharmaceutical composition for use according to  claim 2 , wherein said administration period is 8 weeks. 
     
     
         10 . The pharmaceutical composition for use according to  claim 2 , wherein said administration period is 26 weeks. 
     
     
         11 . The pharmaceutical composition for use according to  claim 2 , wherein said administration period is 8 months. 
     
     
         12 . The pharmaceutical composition for use according to any preceding claim, wherein the amount of said compound having structure (I), or pharmaceutically acceptable salt thereof, administered to said subject is from about 50 mg/day to about 1000 mg/day. 
     
     
         13 . The pharmaceutical composition for use according to  claim 12 , wherein the amount of the compound having structure (I), or pharmaceutically acceptable salt thereof, administered to said subject is from about 200 mg/day to about 800 mg/day. 
     
     
         14 . The pharmaceutical composition for use according to  claim 12 , wherein the amount of said compound having structure (I), or pharmaceutically acceptable salt thereof, administered to said subject is about 200 mg/day. 
     
     
         15 . The pharmaceutical composition for use according to  claim 12 , wherein the amount of said compound having structure (I), or pharmaceutically acceptable salt thereof, administered to said subject is about 400 mg/day. 
     
     
         16 . The pharmaceutical composition for use according to  claim 12 , wherein the amount of said compound having structure (I), or pharmaceutically acceptable salt thereof, administered to said subject is about 800 mg/day. 
     
     
         17 . The pharmaceutical composition for use according to any one of  claims 1 - 11 , wherein said administering comprises (1) an initial administration of said compound having structure (I), or a pharmaceutically acceptable salt thereof, to said subject at an initial dose; and (2) after said initial administration, a subsequent administration of said compound having structure (I), or a pharmaceutically acceptable salt thereof, to said subject at a subsequent dose, wherein said subsequent dose is greater than said initial dose. 
     
     
         18 . The pharmaceutical composition for use according to  claim 17 , wherein said initial dose is 400 mg/day and said subsequent dose is 800 mg/day. 
     
     
         19 . The pharmaceutical composition for use according to  claim 17 , wherein said initial dose is 200 mg/day and said subsequent dose is 400 mg/day. 
     
     
         20 . The pharmaceutical composition for use according to  claim 19 , wherein said subject is a child weighing less than 50 kg. 
     
     
         21 . The pharmaceutical composition for use according to any one of  claims 17 - 20 , wherein said initial administration has a duration of 2 weeks. 
     
     
         22 . The pharmaceutical composition for use according to any one of  claims 1 - 11 , wherein said administering comprises (1) an initial administration of said compound having structure (I), or a pharmaceutically acceptable salt thereof, to said subject for 1-3 weeks at 400 mg/day; and (2) after said initial administration, a subsequent administration of said compound having structure (I), or a pharmaceutically acceptable salt thereof, to said subject at 800 mg/day. 
     
     
         23 . The pharmaceutical composition for use according to any one of  claims 1 - 11 , wherein said administering comprises (1) an initial administration of said compound having structure (I), or a pharmaceutically acceptable salt thereof, to said subject for 1-3 weeks at 200 mg/day; and (2) after said initial administration, a subsequent administration of said compound having structure (I), or a pharmaceutically acceptable salt thereof, to said subject at 400 mg/day. 
     
     
         24 . The pharmaceutical composition for use according to  claim 23 , wherein said subject is a child weighing less than 50 kg. 
     
     
         25 . The pharmaceutical composition for use according to any one of  claims 1 - 11 :
 wherein said administering comprises (1) an initial administration of said compound having structure (I), or a pharmaceutically acceptable salt thereof, to said subject at an initial dose; and (2) after said initial administration, a subsequent administration of said compound having structure (I), or a pharmaceutically acceptable salt thereof, to said subject at a subsequent dose, wherein said subsequent dose is greater than said initial dose; and   the method further comprises measuring the blood pressure of said subject before the subsequent administration.   
     
     
         26 . The pharmaceutical composition for use according to  claim 25 , wherein said initial dose is 400 mg/day and said subsequent dose is 800 mg/day. 
     
     
         27 . The pharmaceutical composition for use according to  claim 25 , wherein said initial dose is 200 mg/day and said subsequent dose is 400 mg/day. 
     
     
         28 . The pharmaceutical composition for use according to  claim 27 , wherein said subject is a child weighing less than 50 kg. 
     
     
         29 . The pharmaceutical composition for use according to any one of  claims 25 - 28 , wherein said initial administration has a duration of 1-3 weeks. 
     
     
         30 . The pharmaceutical composition for use according to any one of  claims 1 - 11 :
 wherein said administering comprises (1) an initial administration of said compound having structure (I), or a pharmaceutically acceptable salt thereof, to said subject for 1-3 weeks at 400 mg/day; and (2) after said initial administration, a subsequent administration of said compound having structure (I), or a pharmaceutically acceptable salt thereof, to said subject at 800 mg/day; and   the method further comprises measuring the blood pressure of said subject before said subsequent administration.   
     
     
         31 . The pharmaceutical composition for use according to any one of  claims 1 - 11 :
 wherein said administering comprises (1) an initial administration of said compound having structure (I), or a pharmaceutically acceptable salt thereof, to said subject for 1-3 weeks at 200 mg/day; and (2) after said initial administration, a subsequent administration of said compound having structure (I), or a pharmaceutically acceptable salt thereof, to said subject at 400 mg/day; and   the method further comprises measuring the blood pressure of said subject before said subsequent administration.   
     
     
         32 . The pharmaceutical composition for use according to  claim 31 , wherein said subject is a child weighing less than 50 kg. 
     
     
         33 . The pharmaceutical composition for use according to any preceding claim, wherein said compound has structure (I). 
     
     
         34 . The pharmaceutical composition for use according to any preceding claim, further comprising administering to said subject one or more additional therapeutic agents. 
     
     
         35 . The pharmaceutical composition for use according to any preceding claim, wherein said kidney disease or disorder is a disorder related to glomerular function. 
     
     
         36 . The pharmaceutical composition for use according to any preceding claim, wherein said kidney disease or disorder is focal segmental glomerulosclerosis (FSGS). 
     
     
         37 . The pharmaceutical composition for use according to  claim 36 , wherein said FSGS is primary FSGS. 
     
     
         38 . The pharmaceutical composition for use according to  claim 36 , wherein said FSGS is secondary FSGS. 
     
     
         39 . The pharmaceutical composition for use according to  claim 36 , wherein said FSGS is genetic FSGS. 
     
     
         40 . The pharmaceutical composition for use according to any one of  claims 1 - 35 , wherein said kidney disease or disorder is IgA nephropathy. 
     
     
         41 . The pharmaceutical composition for use according to any one of  claims 1 - 35 , wherein said kidney disease or disorder is idiopathic membranous nephropathy (IMN). 
     
     
         42 . The pharmaceutical composition for use according to any one of  claims 1 - 35 , wherein said kidney disease or disorder is diabetic nephropathy. 
     
     
         43 . The pharmaceutical composition for use according to any one of  claims 1 - 35 , wherein said kidney disease or disorder is Alport syndrome. 
     
     
         44 . The pharmaceutical composition for use according to any one of  claims 1 - 35 , wherein said kidney disease or disorder is lupus nephritis.