Sustained-release dosage forms of ruxolitinib
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.
1. A method of treating a disease selected from myelofibrosis, polycythemia vera, and graft versus host disease in a human patient in need thereof, comprising administering to the patient an oral sustained-release dosage form once per day, wherein the oral sustained-release dosage form comprises:
ruxolitinib phosphate, and
from 10% to 30% by weight of a sustained-release matrix former, which is hydroxypropyl methylcellulose,
wherein the ruxolitinib phosphate is present in the 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 (C max ) to mean 12-hour plasma concentration (C 12 h ) of ruxolitinib of 10 or less.
2. The method of claim 1 , wherein the ruxolitinib phosphate is present in the dosage form in an amount of 10 mg on a free base basis.
3. The method of claim 1 , wherein the ruxolitinib phosphate is present in the dosage form in an amount of 20 mg on a free base basis.
4. The method of claim 1 , wherein the ruxolitinib phosphate is present in the dosage form in an amount of 30 mg on a free base basis.
5. The method of claim 1 , wherein the ruxolitinib phosphate is present in the dosage form in an amount of 40 mg on a free base basis.
6. The method of claim 1 , wherein the ruxolitinib phosphate is present in the dosage form in an amount of 50 mg on a free base basis.
7. The method of claim 1 , wherein the disease is myelofibrosis.
8. The method of claim 7 , wherein the myelofibrosis is primary myelofibrosis (PMF), postpolycythemia vera myelofibrosis (PV-MF), or post-essential thrombocythemia myelofibrosis (post ET-MF).
9. The method of claim 2 , wherein the disease is myelofibrosis.
10. The method of claim 3 , wherein the disease is myelofibrosis.
11. The method of claim 4 , wherein the disease is myelofibrosis.
12. The method of claim 5 , wherein the disease is myelofibrosis.
13. The method of claim 6 , wherein the disease is myelofibrosis.
14. The method of claim 1 , wherein the disease is polycythemia vera.
15. The method of claim 2 , wherein the disease is polycythemia vera.
16. The method of claim 3 , wherein the disease is polycythemia vera.
17. The method of claim 4 , wherein the disease is polycythemia vera.
18. The method of claim 1 , wherein the disease is polycythemia vera.
19. The method of claim 6 , wherein the disease is polycythemia vera.
20. The method of claim 1 , wherein the disease is graft versus host disease.
21. The method of claim 2 , wherein the disease is graft versus host disease.
22. The method of claim 3 , wherein the disease is graft versus host disease.
23. The method of claim 4 , wherein the disease is graft versus host disease.
24. The method of claim 5 , wherein the disease is graft versus host disease.
25. The method of claim 6 , wherein the disease is graft versus host disease.
26. The method of claim 1 , wherein administration of the dosage form to a human results in a ratio of mean peak plasma concentration (C max ) to mean 12-hour plasma concentration (C 12h ) of ruxolitinib of 1 to 10.
27. The method of claim 1 , wherein administration of the sustained-release dosage form to a human results in a ratio of mean peak plasma concentration (C max ) to mean 12-hour plasma concentration (C 12h ) of ruxolitinib of 2 to 7.
28. The method of claim 1 , wherein administration of the dosage form to a human results in a mean half-life (t 1/2 ) of from 3.5 hours to 11 hours.
29. The method of claim 1 , wherein administration of the dosage form to a human results in a mean half-life (t 1/2 ) of from 4 hours to 8 hours.
30. The method of claim 1 , wherein the dosage form is a tablet or a capsule.