Solid-state form of AMG 706 and pharmaceutical compositions thereof

Abstract

The anti-angiogenic drug AMG 706 is provided in amorphous form. Also provided is AMG 706 drug substance wherein the AMG 706 is present, in at least a detectable amount, as amorphous AMG 706. Also provided is an AMG 706-crystallization inhibitor composite comprising particles of amorphous AMG 706 or a AMG 706 drug substance of the invention in intimate association with one or more crystallization inhibitors, for example polymers. Also provided is a pharmaceutical composition comprising such an AMG 706-crystallization inhibitor composite and one or more excipients. Also provided are processes for preparing amorphous AMG 706, AMG 706 drug substance of the invention, an AMG 706-crystallization inhibitor composite of the invention, and a pharmaceutical composition of the invention. Also provided is a method of treating a medical condition or disorder in a subject where treatment with an anti-angiogenic is indicated, comprising administering, for example orally, a composition of the invention in a therapeutically effective amount.

1 . An amorphous form of a compound wherein said compound is AMG706. 
     
     
         2 . The amorphous form of  claim 1 , wherein said amorphous form exhibits a glass transition measurable by differential scanning calorimetry. 
     
     
         3 . The amorphous form of  claim 1  wherein said amorphous form exhibits a differential scanning calorimetry thermogram glass transition at about 110° C. 
     
     
         4 . The amorphous form of  claim 1  wherein said amorphous form exhibits a differential scanning calorimetry thermogram exotherm between about 150° C. to about 160° C. 
     
     
         5 . A pharmaceutical composition comprising amorphous AMG 706 in a total AMG 706 dosage amount of about 25 mg to about 200 mg, and one or more pharmaceutically acceptable excipients, wherein said amorphous AMG 706 exhibits a glass transition measurable by differential scanning calorimetry. 
     
     
         6 . Amorphous AMG 706 prepared by a lyophilization method. 
     
     
         7 . Amorphous AMG 706 prepared by a spray drying method.