Solid forms of a plasma kallikrein inhibitor and salts thereof

Abstract

New solid forms of the plasma kallikrein inhibitor, 1-({4-[(5-fluoro-2-oxopyridin yl)methyl]phenyl}methyl)-N-[(3-fluoro-4-methoxypyridin-2-yl)methyl]-3-(methoxymethyl)pyrazole carboxamide and its salts, are described.

What is claimed is: 
     
         1 . A method of treating a disease or condition mediated by plasma kallikrein, said method comprising administering to a mammal in need of such treatment a therapeutically effective amount of a solid form of the hydrochloride salt of the compound of Formula A, 
       
         
           
           
               
               
           
         
       
       which exhibits at least the following characterising X-ray powder diffraction peaks (Cu Kα radiation, expressed in degrees 2θ) at approximately 10.4, 15.6, 16.7, and 20.8. 
     
     
         2 . The method according to  claim 1 , wherein the disease or condition mediated by plasma kallikrein is impaired visual acuity, diabetic retinopathy, retinal vascular permeability associated with diabetic retinopathy, diabetic macular edema, hereditary angioedema, retinal vein occlusion, diabetes, pancreatitis, cerebral haemorrhage, nephropathy, cardiomyopathy, neuropathy, inflammatory bowel disease, arthritis, inflammation, septic shock, hypotension, cancer, adult respiratory distress syndrome, disseminated intravascular coagulation, blood coagulation during cardiopulmonary bypass surgery or bleeding from post-operative surgery. 
     
     
         3 . The method according to  claim 1 , wherein the disease or condition mediated by plasma kallikrein is retinal vascular permeability associated with diabetic retinopathy, diabetic macular edema or hereditary angioedema. 
     
     
         4 . The method according to  claim 1 , wherein the disease or condition mediated by plasma kallikrein is selected from retinal vascular permeability associated with diabetic retinopathy, and diabetic macular edema. 
     
     
         5 . The method according to  claim 1 , wherein the disease or condition mediated by plasma kallikrein is hereditary angioedema. 
     
     
         6 . The method according to  claim 1 , wherein the disease or condition mediated by plasma kallikrein is diabetic macular edema. 
     
     
         7 . The method according to  claim 4 , wherein the solid form is administered in a form suitable for injection into the ocular region of a patient, in particular, in a form suitable for intra-vitreal injection. 
     
     
         8 . The method according to  claim 1 , wherein the solid form has an X-ray powder diffraction pattern substantially the same as that shown in  FIG.  6   . 
     
     
         9 . A method of treating a disease or condition mediated by plasma kallikrein, said method comprising administering to a mammal in need of such treatment a therapeutically effective amount of a solid form of the hydrochloride salt of the compound of Formula A, 
       
         
           
           
               
               
           
         
       
       having an X-ray powder diffraction pattern substantially the same as that shown in  FIG.  6   . 
     
     
         10 . The method according to  claim 9 , wherein the disease or condition mediated by plasma kallikrein is impaired visual acuity, diabetic retinopathy, retinal vascular permeability associated with diabetic retinopathy, diabetic macular edema, hereditary angioedema, retinal vein occlusion, diabetes, pancreatitis, cerebral haemorrhage, nephropathy, cardiomyopathy, neuropathy, inflammatory bowel disease, arthritis, inflammation, septic shock, hypotension, cancer, adult respiratory distress syndrome, disseminated intravascular coagulation, blood coagulation during cardiopulmonary bypass surgery or bleeding from post-operative surgery. 
     
     
         11 . The method according to  claim 9 , wherein the disease or condition mediated by plasma kallikrein is retinal vascular permeability associated with diabetic retinopathy, diabetic macular edema or hereditary angioedema. 
     
     
         12 . The method according to  claim 9 , wherein the disease or condition mediated by plasma kallikrein is selected from retinal vascular permeability associated with diabetic retinopathy, and diabetic macular edema. 
     
     
         13 . The method according to  claim 9 , wherein the disease or condition mediated by plasma kallikrein is hereditary angioedema. 
     
     
         14 . The method according to  claim 9 , wherein the disease or condition mediated by plasma kallikrein is diabetic macular edema. 
     
     
         15 . The method according to  claim 12 , wherein the solid form is administered in a form suitable for injection into the ocular region of a patient, in particular, in a form suitable for intra-vitreal injection.