Treatment of osteoarthritis
Provided are compositions and methods for treating osteoarthritis including intra-articular administration of a compound of Formula (I) including amorphous and polymorph forms thereof.
1. A method for treating osteoarthritis in a subject in need thereof, the method comprising intra-articular administration of a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I),
or a pharmaceutically acceptable salt thereof; wherein the compound of Formula (I) is substantially present as a non-stoichiometric hydrate of Form 1 having between 1% and 20% by weight water; wherein less than about 20% by weight of the amount of the compound of Formula (I) in the composition is polymorph Form 9 having X-ray powder diffraction pattern comprising peaks at °2θ values of 4.9±0.2, 18.6±0.2, and 21.1±0.2; wherein the subject has a total WOMAC score of 36 to 72 and/or a Kellgren-Lawrence grade of 2 or 3.
2. The method of claim 1 , wherein the method results in an increase in the joint space width in the joint surrounding the point of intraarticular administration.
3. The method of claim 1 , wherein the method results in an increase in the cartilage thickness in the joint surrounding the point of intraarticular administration.
4. The method of claim 1 , wherein the method results in a decrease in the WOMAC total score in the subject.
5. The method of claim 1 , wherein the method results in a decrease in the WOMAC function score in the subject.
6. The method of claim 1 , wherein the method results in a decrease in the WOMAC pain score in the subject.
7. The method of claim 1 , wherein the method results in a decrease in the WOMAC stiffness score in the subject.
8. The method of claim 1 , wherein the intraarticular administration is ultrasound guided.
9. The method of claim 1 , wherein the composition is administered once.
10. The method of claim 1 , wherein the composition is administered more than once with each injection separated by at least 3 months.
11. The method of claim 1 , wherein the composition is administered more than once with each injection separated by 3 months to 60 months.
12. The method of claim 1 , wherein the composition is administered more than once with each injection separated by at least 4 weeks.
13. The method of claim 1 , wherein the plasma concentration of the compound of Formula (I) in the subject is less than about 0.1 ng/mL when measured 4 hours after administration of the composition.
14. The method of claim 1 , wherein the compound of Formula (I) is not substantially systemically absorbed 4 hours after administration.
15. The method of claim 1 , wherein the subject is diagnosed or identified as having moderate to severe symptomatic knee osteoarthritis, and wherein the composition is intra-articularly administered to at least one knee of the subject.