METHODS OF TREATING A BRUTON'S TYROSINE KINASE DISEASE OR DISORDER
The present invention provides methods of treating, stabilizing or lessening the severity or progression of a disease or disorder associated with BTK.
1 . A method of preventing, treating, stabilizing or lessening the severity or progression of an arthritic condition, the method comprising administering to a patient in need thereof a pharmaceutically acceptable composition comprising a therapeutically effective amount of N-(3-(5-fluoro-2-(4-(2-methoxyethoxyl)phenylamino)pyrimidin-4-ylamino)phenyl)acrylamide (1):
or a pharmaceutically acceptable salt thereof.
2 . The method according to claim 1 , wherein the therapeutically effective amount of Compound 1 is about 125 mg BID to about 250 mg BID.
3 . The method according to claim 1 , wherein the therapeutically effective amount of Compound 1 is about 125 mg to about 375 mg.
4 . The method according to claim 3 , wherein the therapeutically effective amount of Compound 1 is about 125 mg QD.
5 . The method according to claim 3 , wherein the therapeutically effective amount of Compound 1 is about 375 mg.
6 . The method according to claim 5 , wherein Compound 1 is administered as two separate doses consisting of about 250 mg and about 125 mg.
7 . The method according to claim 6 , wherein the 375 mg dose of Compound 1 is administered according to the following dosing schedule:
(i) about 250 mg administered in the morning; and
(ii) about 125 mg administered in the evening.
8 . The method according to claim 7 , wherein the 250 mg dose is administered to a patient who has fasted prior to administration.
9 . The method according to claim 7 or 8 , wherein the 125 mg dose is administered H.S.
10 . The method according to any of claims 1 - 9 , wherein the arthritic condition is selected from osteoarthritis, rheumatoid arthritis, fibromyalgia, gout, ankylosing spondylitis, scleroderma, psoriatic arthritis, Sjogren's syndrome, Still's disease, Paget's disease, myositis, Lyme disease and juvenile idiopathic arthritis.
11 . The method according to claim 10 , wherein the arthritic condition is rheumatoid arthritis.
12 . The method according to any of claims 1 - 11 , wherein the pharmaceutically acceptable composition is formulated as an oral dosage form.
13 . The method according to claim 1 , wherein the pharmaceutically acceptable composition is administered twice a day.
14 . The method according to any of claims 1 - 13 , wherein the pharmaceutically acceptable composition is administered for at least one 28-day cycle.
15 . The method according to any of claims 1 - 14 , wherein Compound 1 is administered as a salt.
16 . The method according to claim 15 , wherein the salt is a benzenesulfonic acid salt.
17 . The method according to claim 16 , wherein the composition comprises from about 10% to about 50% N-(3-(5-fluoro-2-(4-(2-methoxyethoxyl)phenylamino)pyrimidin-4-ylamino)phenyl)acrylamide besylate.
18 . The method according to claim 17 , wherein the composition comprises about 42% N-(3-(5-fluoro-2-(4-(2-methoxyethoxyl)phenylamino)pyrimidin-4-ylamino)phenyl)acrylamide besylate.
19 . The method according to claim 17 or claim 18 , wherein the composition comprises from about 5% to about 15% by weight of wetting agent.
20 . The method according to claim 19 , wherein the composition comprises about 10% by weight of wetting agent.
21 . The method according to claim 19 or 20 , wherein the wetting agent is selected from poloxamer, polyoxyethylene ethers, polyoxyethylene sorbitan fatty acid esters polyoxyethylene fatty acid esters, polyethylene glycol fatty acid esters, polyoxyethylene hydrogenated castor oil, polyoxyethylene alkyl ether, polysorbates, cetyl alcohol, glycerol fatty acid esters, polyoxymethylene stearate, sodium lauryl sulfate, sorbitan fatty acid esters, sucrose fatty acid esters, benzalkonium chloride, polyethoxylated castor oil, and docusate sodium.
22 . The method according to claim 21 , wherein the wetting agent is a poloxamer.
23 . The method according to claim 22 , wherein the poloxamer is poloxamer 407.
24 . The method according to any of claims 1 - 23 , wherein the therapeutically effective amount is about 125 mg BID.
25 . The method according to any of claims 1 - 23 , wherein the therapeutically effective amount is about 250 mg BID.