Claims for Patent: 10,874,616

Summary for Patent: 10,874,616

Title:	Sustained-release dosage forms of ruxolitinib
Abstract:	The present invention relates to sustained-release formulations and dosage forms of ruxolitinib, or a pharmaceutically acceptable salt thereof, which are useful in the treatment of Janus kinase-associated diseases such as myeloproliferative disorders.
Inventor(s):	Yong Ni, Bhavnish Parikh, Krishnaswamy Yeleswaram, Susan Erickson-Viitanen, William V. Williams
Assignee:	Incyte Corp , Incyte Holdings Corp
Application Number:	US16/190,883
Patent Claims:	1. An oral sustained-release dosage form comprising: ruxolitinib phosphate, and from about 10% to about 30% by weight of a sustained-release matrix former, which is hydroxypropyl methylcellulose, wherein said ruxolitinib phosphate is present in said dosage form in an amount of 10 to 60 mg on a free base basis; wherein the dosage form is suitable for oral administration; and wherein administration of the dosage form to a human results in a ratio of mean peak plasma concentration (Cmax) to mean 12-hour plasma concentration (C12h) of ruxolitinib of 10 or less. 2. The oral sustained-release dosage form of claim 1, wherein administration of the dosage form to a human results in a mean peak plasma concentration (Cmax) of ruxolitinib of 700 nM or less. 3. The oral sustained-release dosage form of claim 1, wherein administration of the dosage form to a human results in a mean peak plasma concentration (Cmax) of ruxolitinib of 200 to 700 nM. 4. The oral sustained-release dosage form of claim 1, wherein administration of the dosage form to a human results in a mean peak plasma concentration (Cmax) of ruxolitinib of 300 to 400 nM. 5. The oral sustained-release dosage form of claim 1, wherein administration of the dosage form to a human state results in a mean time to peak plasma concentration (Tmax) of ruxolitinib of 1.5 hours or more. 6. The oral sustained-release dosage form of claim 1, wherein administration of the dosage form to a human results in a mean time to peak plasma concentration (Tmax) of ruxolitinib of 1.5 hours to 5 hours. 7. The oral sustained-release dosage form of claim 1, wherein administration of the dosage form to a human results in a ratio of mean peak plasma concentration (Cmax) to mean 12-hour plasma concentration (C12h) of ruxolitinib of 4 or less. 8. The oral sustained-release dosage form of claim 1, wherein administration of the dosage form to a human results in a mean half-life (t1/2) of from 4 hours to 8 hours. 9. The oral sustained-release dosage form of claim 1, wherein administration of a single dose of the dosage form to a human results in mean bioavailability (AUC0-∞) of ruxolitinib of 3000 to 4000 nM*h. 10. The oral sustained-release dosage form of claim 1, wherein administration of a single dose of the dosage form to a human results in mean bioavailability (AUC0-∞) of ruxolitinib of 3100 to 3800 nM*h. 11. The oral sustained-release dosage form of claim 1, which is in the form of a tablet or capsule. 12. The oral sustained-release dosage form of claim 1, wherein administration to a human results in a ruxolitinib plasma level of 75 to 500 nM for 8 hours. 13. The oral sustained-release dosage form of claim 1, wherein administration to a human results in a ruxolitinib plasma level of 75 to 500 nM for 12 hours. 14. The oral sustained-release dosage form of claim 1, wherein administration of said dosage form to a human once-daily for 16 weeks results in a mean decrease in mean platelet count from baseline of no more than 100×109/L. 15. The oral sustained-release dosage form of claim 14, wherein administration of said dosage form to a human once-daily for 16 weeks results in a mean decrease in mean platelet count from baseline of no more than 80×109/L. 16. The oral sustained-release dosage form of claim 14, wherein administration of said dosage form to a human once-daily for 16 weeks results in a mean decrease in mean platelet count from baseline of no more than 60×109/L. 17. The oral sustained-release dosage form of claim 14, wherein administration of said dosage form to a human once-daily for 16 weeks results in a mean decrease in mean platelet count from baseline of no more than 40×109/L. 18. The oral sustained-release dosage form of claim 1, wherein administration of said dosage form to a human once-daily for 16 weeks results in a mean decrease in mean hemoglobin from baseline of no more than 15 g/L. 19. The oral sustained-release dosage form of claim 18, wherein administration of said dosage form to a human once-daily for at least 16 weeks results in a mean decrease in mean hemoglobin from baseline of no more than 10 g/L. 20. The oral sustained-release dosage form of claim 18, wherein administration of said dosage form to a human once-daily for 16 weeks results in a mean decrease in mean hemoglobin from baseline of no more than 8 g/L. 21. The oral sustained-release dosage form of claim 18, wherein administration of said dosage form to a human once-daily for 16 weeks results in a mean decrease in mean hemoglobin from baseline of no more than 6 g/L. 22. The oral sustained-release dosage form of claim 1, wherein said ruxolitinib, or pharmaceutically acceptable salt thereof, is present in the dosage form in an amount of 10 mg on a free base basis. 23. The oral sustained-release dosage form of claim 1, wherein said ruxolitinib, or pharmaceutically acceptable salt thereof, is present in the dosage form in an amount of 12.5 mg on a free base basis. 24. The oral sustained-release dosage form of claim 1, wherein said ruxolitinib, or pharmaceutically acceptable salt thereof, is present in the dosage form in an amount of 20 mg on a free base basis. 25. The oral sustained-release dosage form of claim 1, wherein said ruxolitinib, or pharmaceutically acceptable salt thereof, is present in the dosage form in an amount of 30 mg on a free base basis. 26. The oral sustained-release dosage form of claim 1, wherein said ruxolitinib, or pharmaceutically acceptable salt thereof, is present in the dosage form in an amount of 37.5 mg on a free base basis. 27. The oral sustained-release dosage form of claim 1, wherein said ruxolitinib, or pharmaceutically acceptable salt thereof, is present in the dosage form in an amount of 40 mg on a free base basis. 28. The oral sustained-release dosage form of claim 1, wherein said ruxolitinib, or pharmaceutically acceptable salt thereof, is present in the dosage form in an amount of 50 mg on a free base basis. 29. The oral sustained-release dosage form of claim 1, wherein said ruxolitinib, or pharmaceutically acceptable salt thereof, is present in the dosage form in an amount of 60 mg on a free base basis. 30. The oral sustained-release dosage form of claim 1, wherein administration of the dosage form to a human results in a ratio of mean peak plasma concentration (Cmax) to mean 12-hour plasma concentration (C12h) of ruxolitinib of 6 or less. 31. The oral sustained-release dosage form of claim 1, wherein administration of the dosage form to a human results in a ratio of mean peak plasma concentration (Cmax) to mean 12-hour plasma concentration (C12h) of ruxolitinib of 5 or less. 32. The oral sustained-release dosage form of claim 1, wherein administration of the dosage form to a human results in a ratio of mean peak plasma concentration (Cmax) to mean 12-hour plasma concentration (C12h) of ruxolitinib of 1 to 10. 33. The oral sustained-release dosage form of claim 1, wherein administration of the dosage form to a human results in a ratio of mean peak plasma concentration (Cmax) to mean 12-hour plasma concentration (C12h) of ruxolitinib of 2 to 7. 34. An oral sustained-release oral dosage form, comprising: ruxolitinib phosphate, and from 10% to 30% by weight of a sustained-release matrix former, which is hydroxypropyl methylcellulose, wherein said ruxolitinib phosphate is present in said dosage form in an amount of 10 to 60 mg on a free base basis; wherein the dosage form is suitable for oral administration; wherein administration of said dosage form to a human results in a ratio of mean peak plasma concentration (Cmax) to mean 12-hour plasma concentration (C12h) of ruxolitinib of 10 or less; and wherein administration of the dosage form to a human results in a mean half-life (t1/2) of from 3.5 hours to 11 hours. 35. The oral sustained-release dosage form of claim 34, wherein administration of the dosage form to a human results in a ratio of mean peak plasma concentration (Cmax) to mean 12-hour plasma concentration (C12h) of ruxolitinib of 2 to 7. 36. The oral sustained-release dosage form of claim 35, wherein administration of the dosage form to a human patient results in a reduction in thrombocytopenia or anemia relative to an immediate-release dosing regimen.