KINASE INHIBITOR SALTS AND COMPOSITIONS THEREOF
The present invention relates methods for treating chronic myeloid leukemia and/or lymphoblastic leukemia by orally administering to a patient in need of such a therapeutic amount of dasatinib lauryl sulfate salt, preferably in a tablet, capsule or suspension form. The method allows the administration of the therapeutic amount of dasatinib lauryl sulfate salt a fed state or a fasted state and the administration does not exhibit a food effect.
1 . A method for treating chronic myeloid leukemia and/or lymphoblastic leukemia comprising orally administering to a patient in need of such therapy a dasatinib lauryl sulfate dosage form comprising a therapeutic amount of dasatinib lauryl sulfate salt.
2 . The method of claim 1 wherein the dasatinib lauryl sulfate dosage form is administered to the patient in a fed state.
3 . The method of claim 1 wherein the dasatinib lauryl sulfate dosage form is administered to the patient is a fasted state.
4 . The method of claim 1 wherein the dasatinib lauryl sulfate dosage form is administered to the patient in a fed state or a fasted state and the administration does not exhibit a food effect.
5 . The method of claim 1 wherein the therapeutic amount of dasatinib lauryl sulfate salt in the dosage form is equivalent to about 5 mg to about 250 mg of dasatinib free base.
6 . The method of claim 1 wherein the patient's dasatinib C max does not change by more than 40% when the dasatinib lauryl sulfate dosage form is administered to the patient in a fed state compared to when the dasatinib lauryl sulfate dosage form is administered to the patient in a fasted state.
7 . The method of claim 6 wherein the patient's dasatinib C max is a mean maximum dasatinib plasma concentration.
8 . The method of claim 1 wherein the patient's dasatinib AUC 0-∞ or dasatinib AUC 0-t does not change by more than 40% when the dasatinib lauryl sulfate dosage form is administered to the patient in a fed state compared to when the dasatinib lauryl sulfate dosage form is administered to the patient in a fasted state.
9 . The method of claim 8 wherein the patient's dasatinib AUC 0-∞ or dasatinib AUC 0-t is a mean dasatinib AUC 0-∞ or a mean dasatinib AUC 0-t .
10 . The method of claim 1 wherein the dasatinib lauryl sulfate dosage form exhibits a C max fed /C max fast ratio of about 0.60 to about 2.5 wherein the C max fed is a mean maximum dasatinib plasma concentration obtained by administering a single dose of the dasatinib lauryl sulfate dosage form to a population of human patients or healthy human subjects in a fed state and the C max fast is a mean maximum dasatinib plasma concentration obtained by administering a single dose of the dasatinib lauryl sulfate dosage form to the patients or subjects in a fasted state.
11 . The method of claim 1 wherein the dasatinib lauryl sulfate dosage form exhibits an AUC 0-∞ fed /AUC 0-∞ fast ratio of about 0.60 to about 2.5 wherein the AUC 0-∞ fed is a mean AUC 0-∞ obtained from the time of administration of a single dose of the dasatinib lauryl sulfate dosage form to a population of human patients or healthy human subjects in a fed state to infinity and the AUC 0-∞ fast is a mean AUC 0-∞ obtained from the time of administration of a single dose of the dasatinib lauryl sulfate dosage form to the patients or subjects in a fasted state to infinity.
12 . The method of claim 1 wherein the dasatinib lauryl sulfate dosage form is a tablet, capsule or suspension.
13 . A method for treating chronic myeloid leukemia comprising orally administering to a patient in need of such therapy a dasatinib lauryl sulfate dosage form comprising a therapeutic amount of dasatinib lauryl sulfate salt and at least one pharmaceutically acceptable excipient wherein the patient's dasatinib AUC 0-∞ or dasatinib AUC 0-t does not change by more than 40% when the dasatinib lauryl sulfate dosage form is administered to the patient in a fed state compared to when the dasatinib lauryl sulfate dosage form is administered to the patient in a fasted state and wherein the therapeutic amount of dasatinib lauryl sulfate salt in the dasatinib lauryl sulfate dosage form is equivalent to about 5 mg to about 250 mg of dasatinib free base.
14 . The method of claim 13 wherein the dasatinib lauryl sulfate dosage form is a tablet, capsule or suspension.
15 . The method of claim 13 wherein the patient's dasatinib AUC 0-∞ or dasatinib AUC 0-t is a mean dasatinib AUC 0-∞ or a mean dasatinib AUC 0-t .
16 . The method of claim 13 wherein the dasatinib lauryl sulfate salt comprises crystalline dasatinib lauryl sulfate characterized by an x-ray powder diffraction (XRPD) pattern with four or more 2θ peaks selected from the group consisting of 6.5±0.2, 9.5±0.2, 10.2±0.2, 12.7±0.2, 17.1±0.2, 18.1±0.2, 19.1±0.2, 21.1±0.2, 22.2±0.2, 24.1±0.2, 24.7±0.2 and 28.5±0.2.
17 . The method of claim 13 wherein the dasatinib lauryl sulfate salt comprises crystalline dasatinib lauryl sulfate characterized by an x-ray powder diffraction (XRPD) pattern with four or more 2θ peaks selected from the group consisting of 6.6±0.2, 12.4±0.2, 17.1±0.2, 18.2±0.2, 19.0±0.2, 21.3±0.2, 22.3±0.2, 24.1±0.2, 24.8±0.2, and 27.5±0.2.
18 . The method of claim 13 wherein the dasatinib lauryl sulfate salt comprises crystalline dasatinib lauryl sulfate characterized by an x-ray powder diffraction (XRPD) pattern with four or more 2θ peaks selected from the group consisting of 6.3±0.2, 9.5±0.2, 12.7±0.2, 15.9±0.2, 17.0±0.2, 19.0±0.2, 21.0±0.2, 22.2±0.2, 24.6±0.2 and 31.2±0.2.
19 . The method of claim 13 wherein the dasatinib lauryl sulfate salt comprises crystalline dasatinib lauryl sulfate characterized by an x-ray powder diffraction (XRPD) pattern with four or more 2θ peaks selected from the group consisting of 6.9±0.2, 9.9±0.2, 10.5±0.2, 13.1±0.2, 17.1±0.2, 17.4±0.2, 18.4±0.2, 19.4±0.2, 21.5±0.2, 22.6±0.2, 24.4±0.2, and 25.0±0.2.
20 . The method of claim 13 wherein the dasatinib lauryl sulfate salt comprises amorphous dasatinib lauryl sulfate.