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-1-carboxamide, solid state forms thereof, and corresponding pharmaceutical compositions, methods of treatment (including treatment of rheumatoid arthritis and various spondyloarthritic conditions, including types of axial spondyloarthritis (axSpA)), kits, methods of synthesis, and products-by-process. In various aspects, provided are methods for treating active non-radiographic axSpA (nr-axSpA) and methods for treating active ankylosing spondylitis (AS).
1. A method of treating a human patient having a spondyloarthropathy, comprising orally administering once daily to the patient a solid dosage form comprising (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) in an amount sufficient to deliver to the patient 15 mg of Compound 1 free base equivalent.
2. The method of claim 1 , wherein the patient is an adult patient.
3. The method of claim 1 , wherein the patient has had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs.
4. The method of claim 1 , wherein the patient has had an inadequate response or intolerance to one or more non-steroidal anti-inflammatory drugs (NSAIDs).
5. The method of claim 1 , wherein the patient has had an inadequate response or intolerance to an anti-TNF biologic agent.
6. The method of claim 1 , wherein the spondyloarthropathy is ankylosing spondylitis.
7. A method of treating a human patient having a spondyloarthropathy, comprising orally administering once daily to the patient a solid dosage form comprising (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) in an amount sufficient to deliver to the patient 15 mg of Compound 1 free base equivalent, wherein the method results in an Assessment of SpondyloArthritis International Society 40 (ASAS40) response at 14 weeks after the first daily administration.
8. The method of claim 7 , wherein the patient is an adult patient.
9. The method of claim 7 , wherein the patient has had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs.
10. The method of claim 7 , wherein the patient has had an inadequate response or intolerance to one or more non-steroidal anti-inflammatory drugs (NSAIDs).
11. The method of claim 7 , wherein the patient has had an inadequate response or intolerance to an anti-TNF biologic agent.
12. The method of claim 7 , wherein the spondyloarthropathy is ankylosing spondylitis.
13. A method of treating a human patient having active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation, comprising orally administering once daily to the patient a solid dosage form comprising (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) in an amount sufficient to deliver to the patient 15 mg of Compound 1 free base equivalent.
14. The method of claim 13 , wherein the patient is an adult patient.
15. The method of claim 13 , wherein the patient has had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs.
16. The method of claim 13 , wherein the patient has had an inadequate response or intolerance to one or more non-steroidal anti-inflammatory drugs (NSAIDs).
17. The method of claim 13 , wherein the patient has had an inadequate response or intolerance to an anti-TNF biologic agent.
18. A method of treating a human patient having active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation, comprising orally administering once daily to the patient a solid dosage form comprising (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) in an amount sufficient to deliver to the patient 15 mg of Compound 1 free base equivalent, wherein the method results in an Assessment of SpondyloArthritis International Society 40 (ASAS40) response at 14 weeks after the first daily administration.
19. The method of claim 18 , wherein the patient is an adult patient.
20. The method of claim 18 , wherein the patient has had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs.
21. The method of claim 18 , wherein the patient has had an inadequate response or intolerance to one or more non-steroidal anti-inflammatory drugs (NSAIDs).
22. The method of claim 18 , wherein the patient has had an inadequate response or intolerance to an anti-TNF biologic agent.