Cabozantinib compositions and methods of use
AssigneeHanda Oncology, LLC
InventorsFang-Yu Liu, K.C. Sung, Yu Zhang, Shang Wei Qin, John Duan, George Kraft
Life of this patent
Estimating the term…
Abstract
The present invention relates to oral compositions comprising cabozantinib salts and at least one pharmaceutically acceptable excipient and methods of using the oral compositions to increase the oral bioavailability of the cabozantinib and reduce the adverse events associate with the oral administration of cabozantinib. The invention also relates to methods for preparing cabozantinib lauryl sulfate salts.
Claims18
A method for treating a human subject in need of cabozantinib treatment comprising orally administering to the subject once a day a capsule wherein the contents of the capsule comprise:
- (i) about 25 mg to about 45 mg of cabozantinib free base in the form of cabozantinib lauryl sulfate salt;
- and
- (ii) about 50 wt % to about 90 wt % of one or more polyoxyethylene pharmaceutical acceptable excipients with a hydrophilic-lipophilic balance (HLB) value of about 10 or greater selected from the group consisting of wetting agents, emulsifying agents, solubilizing surfactants and combinations thereof;
- and wherein the once daily administration of the capsule under fasted conditions produces a Cmax that is 80% to 125% of an immediate release tablet comprising 60 mg of cabozantinib free base in the form of 76 mg of cabozantinib(S)-malate, microcrystalline cellulose, lactose anhydrous, hydroxypropyl cellulose, croscarmellose sodium, colloidal silicon dioxide, and magnesium stearate and administered once a day under fasted conditions;
- and
- the once daily administration of the capsule under fasted conditions produces an AUC0-72 or AUC0-∞ that is 80% to 125% of the tablet comprising the 76 mg of cabozantinib (S)-malate and administered once a day under fasted conditions.
A method for treating a human subject in need of cabozantinib treatment comprising orally administering to the subject once a day a capsule wherein the contents of the capsule comprise:
- (i) about 16 mg to about 30 mg of cabozantinib free base in the form of cabozantinib lauryl sulfate salt;
- and
- (ii) about 50 wt % to about 90 wt % of one or more polyoxyethylene pharmaceutical acceptable excipients with a hydrophilic-lipophilic balance (HLB) value of about 10 or greater selected from the group consisting of wetting agents, emulsifying agents, solubilizing surfactants and combinations thereof;
- wherein the once daily administration of the capsule under fasted conditions produces a Cmax that is 80% to 125% of an immediate release tablet comprising 40 mg of cabozantinib free base in the form of 51 mg of cabozantinib (S)-malate, microcrystalline cellulose, lactose anhydrous, hydroxypropyl cellulose, croscarmellose sodium, colloidal silicon dioxide, and magnesium stearate and administered once a day under fasted conditions;
- and
- the once daily administration of the capsule under fasted conditions produces an AUC0-72 or AUC0-∞ that is 80% to 125% of the tablet comprising the 51 mg of cabozantinib (S)-malate and administered once a day under fasted conditions.
A method for treating a human subject in need of cabozantinib treatment comprising orally administering to the subject once a day a capsule wherein the contents of the capsule comprise:
- (i) about 8 mg to about 15 mg of cabozantinib free base in the form of cabozantinib lauryl sulfate salt;
- and
- (ii) about 50 wt % to about 90 wt % of one or more polyoxyethylene pharmaceutical acceptable excipients with a hydrophilic-lipophilic balance (HLB) value of about 10 or greater selected from the group consisting of wetting agents, emulsifying agents, solubilizing surfactants and combinations thereof;
- wherein the once daily administration of the capsule under fasted conditions produces a Cmax that is 80% to 125% of an immediate release tablet comprising 20 mg of cabozantinib free base in the form of 25 mg of cabozantinib (S)-malate, microcrystalline cellulose, lactose anhydrous, hydroxypropyl cellulose, croscarmellose sodium, colloidal silicon dioxide, and magnesium stearate and administered once a day under fasted conditions;
- and
- the once daily administration of the capsule under fasted conditions produces an AUC0-72 or AUC0-∞ that is 80% to 125% of the tablet comprising the 25 mg of cabozantinib (S)-malate and administered once a day under fasted conditions.
Dependencies are inferred from the claim text.