DOSAGE FORMS AND METHODS OF TREATMENT USING A TYROSINE KINASE INHIBITOR

• US 20090012085A1
• Filed: 09/12/2006
• Published: 01/08/2009
• Est. Priority Date: 09/20/2005
• Status: Abandoned Application

• Current Assignee: Alfonso Gentile, Charles Michael Baum, Nicoletta Maria Brega, Yazdi Kersi Pithavala
• Original Assignee: Alfonso Gentile, Charles Michael Baum, Nicoletta Maria Brega, Yazdi Kersi Pithavala
• Inventors: Gentile, Alfonso, Pithavala, Yazdi Kersi, Brega, Nicoletta Maria, Baum, Charles Michael
• Application Number:
  US12/067,150
• Publication Number:
  US 20090012085A1
• Time in Patent Office: Days
• US Class Current: 514/235.200
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system

Abstract

This invention provides dosage forms of a compound of formula 1, 5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide, or pharmaceutically acceptable salts or solvates thereof. The invention further provides methods of treating abnormal cell growth in a patient, such as cancers, by administering the dosage forms to the patient. The invention further provides methods of treating an angiogenesis- or VEGF-related ophthalmic disorder in a patient, by administering the dosage form to the patient.

Claims

1. A method of treating cancer in a patient, comprising administering to the patient a compound of formula 1:

or a pharmaceutically acceptable salt or solvate thereof, or a mixture thereof, in an amount of from 5 to 300 mg free base equivalent per day.

2. The method of claim 1, wherein the cancer is selected from the group consisting of a gastrointestinal stromal tumor, renal cell carcinoma, biliary cell carcinoma, thyroid carcinoma, colon adenocarcinoma, alveolar soft tissue carcinoma, thymoma, breast cancer, colorectal cancer, non-small cell lung cancer, a neuroendocrine tumor, small cell lung cancer, mastocytosis, glioma, sarcoma, acute myeloid leukemia, prostate cancer, lymphoma, and pancreatic cancer.

3. The method of claim 1, wherein the amount is from 50 to 250 mg free base equivalent.

4. The method of claim 1, wherein the amount is from 100 to 200 mg free base equivalent.

5. The method of claim 1, wherein the amount is 150 mg free base equivalent or 200 mg free base equivalent.

6. The method of claim 1, wherein the amount is administered on a continuous dosing schedule.

7. The method of any of claim 1, wherein the amount is administered on an intermittent dosing schedule.

8. The method of claim 7, wherein the intermittent dosing schedule comprises a treatment period of from 2 to 4 weeks and a rest period of from 1 to 2 weeks.

9. A method of treating an angiogenesis- or VEGF-related ophthalmic disorder in a patient, comprising administering to the patient a compound of formula 1, or a pharmaceutically acceptable salt or solvate thereof, or a mixture thereof, in an amount of from 5 to 300 mg free base equivalent per day.

10. The method of claim 9, wherein the ophthalmic disorder is age related macular degeneration, choroidal neovascularization, retinopathy, retinitis, uveitis, retinal vein occlusion, iris neovascularization, corneal neovascularization, macular edema, or neovascular glaucoma.

11. A dosage form comprising a compound of formula 1:

or a pharmaceutically acceptable salt or solvate thereof, or a mixture thereof, in an amount of from 5 to 300 mg free base equivalent.

12. The dosage form of claim 11, wherein the amount is from 25 to 300 mg free base equivalent.

13. The dosage form of claim 11, wherein the amount is from 50 to 250 mg free base equivalent.

14. The dosage form of claim 11, wherein the amount is from 100 to 200 mg free base equivalent.

15. The dosage form of claim 11, wherein the dosage form is an oral dosage form.