Processes for the preparation of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]-pyrazin-8-yl)-n-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide and solid state forms thereof
The present disclosure relates to processes for preparing (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine carboxamide, solid state forms thereof, and corresponding pharmaceutical compositions, methods of treatment (including treatment of rheumatoid arthritis), kits, methods of synthesis, and products-by-process.
1. A method of treating moderately to severely active rheumatoid arthritis in a subject in need thereof, comprising orally administering once daily to the subject a tablet comprising a therapeutically effective amount of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide (Compound 1), wherein the therapeutically effective amount is 15 mg, and wherein the subject achieves an ACR50 score at week twelve of treatment.
2. The method of claim 1 , wherein the subject is an adult subject.
3. The method of claim 1 , wherein the subject has had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs.
4. The method of claim 1 , wherein the subject has had an inadequate response or intolerance to methotrexate.
5. The method of claim 1 , wherein the subject has had an inadequate response or intolerance to anti-TNF biologic agent.
6. The method of claim 1 , wherein the therapeutically effective amount of Compound 1 is administered as 15.4 mg of Freebase Hydrate Form C.
7. A method of treating moderately to severely active rheumatoid arthritis in a subject in need thereof, comprising orally administering once daily to the subject a tablet comprising a therapeutically effective amount of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide (Compound 1), wherein the therapeutically effective amount is 15 mg, and wherein the subject achieves an ACR70 score at week twelve of treatment.
8. The method of claim 7 , wherein the subject is an adult subject.
9. The method of claim 7 , wherein the subject has had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs.
10. The method of claim 7 , wherein the subject has had an inadequate response or intolerance to methotrexate.
11. The method of claim 7 , wherein the subject has had an inadequate response or intolerance to an anti-TNF biologic agent.
12. The method of claim 7 , wherein the therapeutically effective amount of Compound 1 is administered as 15.4 mg of Freebase Hydrate Form C.
13. A method of treating moderately to severely active rheumatoid arthritis in a subject in need thereof, comprising orally administering once daily to the subject a tablet comprising a therapeutically effective amount of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide (Compound 1), wherein the therapeutically effective amount is 15 mg, and wherein the subject achieves a DAS28 (CRP) score of <2.6 at week twelve of the treatment.
14. The method of claim 13 , where in the subject is an adult subject.
15. The method of claim 13 , wherein the subject has had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs.
16. The method of claim 13 , wherein the subject has had an inadequate response to methotrexate.
17. The method of claim 13 , wherein the subject has had an inadequate response or intolerance to an anti-TNF biologic agent.
18. The method of claim 13 , wherein the therapeutically effective amount of Compound 1 is administered as 15.4 mg of Freebase Hydrate Form C.
19. A method of treating moderately to severely active rheumatoid arthritis in a subject in need thereof, comprising orally administering once daily to the subject a tablet comprising a therapeutically effective amount of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide, wherein the therapeutically effective amount is 15 mg, and wherein the subject achieves a Clinical Disease Activity Index (CDAI) score of 2.8 or less at week twelve of treatment.
20. The method of claim 19 , wherein the subject is an adult subject.
21. The method of claim 19 , wherein the subject has an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs.
22. The method of claim 19 , wherein the subject has had an inadequate response to methotrexate.
23. The method of claim 19 , wherein the subject has had an inadequate response of intolerance to an anti-TNF biologic agent.
24. The method of claim 19 , wherein the therapeutically effective amount of Compound 1 is administered as 15.4 mg of Freebase Hydrate Form C.