SALTS AND CRYSTALLINE FORMS OF AN APOPTOSIS-INDUCING AGENT
Salts and crystalline forms of 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}-sulfonyl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide are suitable active pharmaceutical ingredients for pharmaceutical compositions useful in treatment of a disease characterized by overexpression of one or more anti-apoptotic Bcl-2 family proteins, for example cancer.
1 . A method for treating a hematopoietic malignancy in a human patient, comprising:
orally administering to the human patient a solid dosage form prepared by dissolving a free base crystalline form of 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}sulfonyl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide (Compound 1) in a pharmaceutically acceptable solvent or mixture of solvents in an amount sufficient to deliver a therapeutically effective amount of Compound 1 to the human patient;
wherein substantially all of the Compound 1 present in the solid dosage form is non-crystalline as determined by powder x-ray diffraction using a diffractometer operated with a copper anode tube (1.5 kW fine focus) at 40 kV and 30 mA and monochromatic Cu-Ka radiation having a wavelength of 1.54178 Å.
2 . The method of claim 1 , wherein the hematopoietic malignancy is a lymphoid malignancy.
3 . The method of claim 2 , wherein the lymphoid malignancy is chronic lymphoid leukemia.
4 . The method of claim 1 , wherein the therapeutically effective amount is 100 mg of Compound 1.