Crystalline composition of tildacerfont and methods of use and preparation thereof

Abstract

Described herein are crystalline composition, methods of making such crystalline composition, pharmaceutical compositions and medicaments comprising such crystalline composition, and methods of using such crystalline composition in the treatment of conditions, diseases, or disorders that would benefit from modulation of Corticotropin-releasing hormone receptor 1 (CRF1).

1 - 30 . (canceled) 
     
     
         31 . A method of treating, preventing, or improving the symptoms of a disease or disorder in a subject in need thereof, comprising administering to the subject a crystalline composition comprising Compound 1: 
       
         
           
           
               
               
           
         
         wherein said crystalline composition is characterized by:
 a) an X-ray diffraction pattern comprising peaks at 10.84±0.2° 2-θ, 15.96 0.2° 2-θ,  23 . 44 ±0.2° 2-θ, or 24.80±0.2° 2-θ, as measured by X-ray powder diffraction using an X-ray wavelength of 0.71073 Å; 
 b) a differential scanning calorimetry (DSC) thermogram comprising an endotherm in the range of about 160° C. to 170° C.; 
 c) a differential scanning calorimetry (DSC) thermogram comprising an endotherm with an onset of about 164° C. and a peak of about 166° C.; 
 d) a thermogravimetric analysis (TGA) thermogram comprising a loss in mass of about 11% over a temperature range of about 25° C. to about 200° C.; or 
 e) combinations thereof. 
 
       
     
     
         32 . The method of  claim 31 , wherein the crystalline composition is characterized by the X-ray diffraction pattern comprising peaks at 10.84±0.2° 2-θ, 15.96±0.2° 2-θ, 23.44±0.2° 2-θ, or 24.80 0.2° 2-θ, as measured by X-ray powder diffraction using an X-ray wavelength of 0.71073 Å. 
     
     
         33 . The method of  claim 32 , wherein the X-ray powder diffraction pattern comprises peaks at 10.84±0.2° 2-θ, 15.96±0.2° 2-θ, 23.44±0.2° 2-θ, and 24.80±0.2° 2-0. 
     
     
         34 . The method of  claim 32 , wherein the X-ray powder diffraction pattern further comprising at least one peak selected from 5.44±0.2° 2-θ, 20.78±0.2° 2-θ, 22.74±0.2° 2-θ, 23.04±0.2° 2-θ, 26.80±0.2° 2-θ, and 28.86±0.2° 2-0. 
     
     
         35 . The method of  claim 32 , wherein the X-ray powder diffraction pattern further comprising at least five peaks selected from 8.82±0.2° 2-θ, 11.70±0.2° 2-θ, 14.60±0.2° 2-θ, 15.56±0.2° 2-θ, 16.70±0.2° 2-θ, 18.82±0.2° 2-θ, 19.18±0.2° 2-θ, 20.02±0.2° 2-θ, 20.50±0.2° 2-θ, 21.72±0.2° 2-θ, 25.52±0.2° 2-θ, 25.92±0.2° 2-θ, 26.94±0.2° 2-θ, and 28.00 0.2° 2-θ. 
     
     
         36 . The method of  claim 31 , wherein the crystalline composition is characterized by a differential scanning calorimetry (DSC) thermogram comprising an endotherm in the range of about 160° C. to 170° C. 
     
     
         37 . The method of  claim 31 , wherein the crystalline composition is characterized by a differential scanning calorimetry (DSC) thermogram comprising an endotherm with an onset of about 164° C. and a peak of about 166° C. 
     
     
         38 . The method of  claim 37 , wherein the crystalline composition is characterized by a melting point of about 166° C. 
     
     
         39 . The method of  claim 31 , wherein the crystalline composition is characterized by a thermogravimetric analysis (TGA) thermogram comprising a loss in mass of about 11% over a temperature range of about 25° C. to about 200° C. 
     
     
         40 . The method of  claim 31 , wherein the disease or disorder is polycystic ovary syndrome (PCOS). 
     
     
         41 . The method of  claim 40 , wherein the PCOS is PCOS with functional ovarian hyperandrogenism and functional adrenal hyperandrogenism (PCOS−FOH+FAH). 
     
     
         42 . The method of  claim 40 , wherein the PCOS is PCOS with functional adrenal hyperandrogenism (PCOS+FAH). 
     
     
         43 . The method of  claim 31 , wherein the disease or disorder is congenital adrenal hyperplasia (CAH). 
     
     
         44 . The method of  claim 43 , wherein the CAH is classic CAH. 
     
     
         45 . The method of  claim 43 , wherein the CAH is non-classical CAH. 
     
     
         46 . The method of  claim 31 , wherein the disease or disorder is testicular adrenal rest tumors (TART) or ovarian adrenal rest tumors (OART). 
     
     
         47 . The method of  claim 31 , wherein the disease or disorder is endometriosis. 
     
     
         48 . The method of  claim 31 , wherein the method further comprises administering to the subject a glucocorticoid. 
     
     
         49 . The method of  claim 48 , wherein the glucocorticoid is beclomethasone, betamethasone, budesonide, cortisone, dexamethasone, hydrocortisone, methylprednisolone, prednisolone, prednisone, or triamcinolone.