JPWO2021212032A5 - - Google Patents

Claims (42)

Amorphous forms of Compound I;

Or a pharma- ceutically acceptable salt, solvate, or solvated salt thereof. The amorphous form of claim 1, wherein Compound I is anhydrous or non-solvated. The amorphous form of claim 1 or 2, wherein Compound I is not present as a pharma- ceutically acceptable salt. The amorphous form of any one of claims 1 to 3, exhibiting an XRPD pattern substantially similar to Figure 7 (third spectrum from the bottom) if the peaks at 27.3±0.2 and 31.7±0.2 degrees 2-theta are excluded. The amorphous form of any one of claims 1 to 4, which exhibits a differential scanning calorimetry (DSC) thermogram including an exothermic peak at about 91°C. The amorphous form of any one of claims 1 to 5, exhibiting a differential scanning calorimetry (DSC) thermogram that includes an endothermic peak with an onset at about 178°C. The amorphous form of any one of claims 1 to 6, exhibiting a glass transition temperature of about 61°C. The amorphous form of any one of claims 1 to 7, exhibiting a thermogravimetric analysis (TGA) thermogram that includes a change in slope beginning at about 280°C. The amorphous form of any one of claims 1 to 8, wherein the amorphous form has a purity of about 95% or greater. The amorphous form of any one of claims 1 to 8, wherein the amorphous form has a purity of about 99% or greater. The amorphous form of claim 1, wherein the amorphous form exhibits an X-ray powder diffraction (XRPD) pattern substantially similar to any one of the patterns shown in Figures 13 and 15. The amorphous form of claim 11, exhibiting an XRPD pattern substantially similar to the patterns labeled SDD-A, SDD-B, SDD-C, SDD-D, or SDD-E in FIG. 13, or the patterns labeled SDD-H, SDD-I, SDD-J, SDD-N, SDD-O, SDD-O, SDD-P, SDD-Q, or SDD-R in FIG. 15. The amorphous form of claim 11 or 12, which exhibits a glass transition temperature (Tg) in the range of about 60°C to about 180°C as measured by differential scanning calorimetry. The amorphous form of claim 11 or 12, which exhibits a glass transition temperature (Tg) in the range of about 60°C to about 90°C as measured by differential scanning calorimetry. The amorphous form of any one of claims 11 to 14, having a purity ranging from about 80% to about 99%. The amorphous form of any one of claims 11 to 14, having a purity of about 95% or more. The amorphous form of any one of claims 11 to 16, comprising less than 10% of a crystalline form of Compound I or a pharma- ceutically acceptable salt, solvate, stereoisomer, or prodrug thereof. The amorphous form of any one of claims 11 to 16, comprising less than 5% of a crystalline form of Compound I or a pharma- ceutically acceptable salt, solvate, stereoisomer, or prodrug thereof. A composition comprising the amorphous form of any one of claims 1 to 18 and a pharma- ceutically acceptable carrier. The composition according to claim 19, wherein the composition is a pharmaceutical solid dispersion composition. 1. A pharmaceutical combination comprising:
a) an amorphous form of Compound I;

or a pharma- ceutically acceptable salt, solvate, or solvated salt thereof, and b) one or more additional therapeutic agents;
23. A pharmaceutical combination comprising: 22. The combination of claim 21, wherein compound I is anhydrous or nonsolvated. The combination according to claim 21 or 22, wherein compound I is not present as a pharma- ceutically acceptable salt. The combination of any one of claims 21-23, wherein the amorphous form exhibits an XRPD pattern substantially similar to Figure 7 (third spectrum from the bottom) if the peaks at 27.3±0.2 and 31.7±0.2 degrees 2-theta are excluded. The combination of any one of claims 21 to 24, wherein the amorphous form exhibits a differential scanning calorimetry (DSC) thermogram that includes an exothermic peak at about 91°C. The combination of any one of claims 21 to 25, wherein the amorphous form exhibits a differential scanning calorimetry (DSC) thermogram that includes an endothermic peak with an onset at about 178°C. The combination according to any one of claims 21 to 26, wherein the amorphous form exhibits a glass transition temperature of about 61°C. The combination of any one of claims 21 to 27, wherein the amorphous form exhibits a thermogravimetric analysis (TGA) thermogram that includes a change in slope beginning at about 280°C. The combination according to any one of claims 21 to 28, wherein the amorphous form has a purity of about 95% or greater. The combination of claim 29, wherein the amorphous form has a purity of about 99% or greater. 22. The combination of claim 21, wherein the amorphous form exhibits an X-ray powder diffraction (XRPD) pattern substantially similar to any one of the patterns shown in Figures 13 and 15. The combination of claim 31, wherein the amorphous form exhibits an XRPD pattern substantially similar to the patterns labeled SDD-A, SDD-B, SDD-C, SDD-D, or SDD-E in FIG. 13, or the patterns labeled SDD-H, SDD-I, SDD-J, SDD-N, SDD-O, SDD-O, SDD-P, SDD-Q, or SDD-R in FIG. 15. The combination of claim 31 or 32, wherein the amorphous form exhibits a glass transition temperature (Tg) in the range of about 60°C to about 180°C as measured by differential scanning calorimetry. The combination of claim 31 or 32, wherein the amorphous form exhibits a glass transition temperature (Tg) in the range of about 60°C to about 90°C as measured by differential scanning calorimetry. The combination of any one of claims 31 to 34, wherein the amorphous form has a purity ranging from about 80% to about 99%. The combination of any one of claims 31 to 34, wherein the amorphous form has a purity of about 95% or greater. The combination of any one of claims 31 to 36, wherein the amorphous form comprises less than 10% of a crystalline form of Compound I or a pharma- ceutically acceptable salt, solvate, stereoisomer, or prodrug thereof. The combination of any one of claims 31 to 37, wherein the amorphous form comprises less than 5% of a crystalline form of Compound I or a pharma- ceutically acceptable salt, solvate, stereoisomer, or prodrug thereof. The combination of any one of claims 21 to 38, wherein the one or more additional therapeutic agents are androgen receptor ligand binding domain inhibitors. The combination of claim 39, wherein the androgen receptor ligand binding domain inhibitor is enzalutamide, apalutamide, darolutamide, bicalutamide, nilutamide, flutamide, ODM-204, or TAS3681. The combination according to any one of claims 21 to 38, wherein the one or more additional therapeutic agents are inhibitors of CYP17. The combination of claim 41, wherein the CYP17 inhibitor is galetrone, abiraterone, or abiraterone acetate.