Processes for the preparation of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-α]pyrrolo[2,3-e]-pyrazin-8-yl)-n-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide and solid state forms therof
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 atopic dermatitis), kits, methods of synthesis, and products-by-process.
1. A method of treating a human patient having moderate to severe atopic dermatitis, comprising orally administering once daily to the patient 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.
2. The method of claim 1 , wherein the patient is an adult.
3. The method of claim 2 , wherein the patient had inadequately responded to treatment with topical corticosteroids or topical calcineurin inhibitors.
4. The method of claim 1 , wherein the method further comprises administering a topical corticosteroid to the patient.
5. The method of claim 1 , wherein the patient has achieved clear or almost clear skin, as measured by an Investigator's Global Assessment score of 0 or 1, at week 16 of said once daily administration.
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 a human patient having moderate to severe atopic dermatitis, comprising orally administering once daily to the patient a tablet comprising a therapeutically effective amount (3 S,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 method results in an Eczema Area and Severity Index (EASI) 75 at 16 weeks after the first daily administration.
8. The method of claim 7 , wherein the patient is an adult.
9. The method of claim 8 , wherein the patient had inadequately responded to treatment with topical corticosteroids or topical calcineurin inhibitors.
10. The method of claim 7 , wherein the method further comprises administering a topical corticosteroid to the patient.
11. The method of claim 7 , wherein the patient has achieved clear or almost clear skin, as measured by an Investigator's Global Assessment score of 0 or 1, at week 16 of said once daily administration.
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 a human patient having moderate to severe atopic dermatitis, comprising orally administering once daily to the patient 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 method results in an Eczema Area and Severity Index (EASI) 90 at 16 weeks after the first daily administration.
14. The method of claim 13 , wherein the patient is an adult.
15. The method of claim 14 , wherein the adult patient had inadequately responded to treatment with topical corticosteroids or topical calcineurin inhibitors.
16. The method of claim 13 , wherein the method further comprises administering a topical corticosteroid to the patient.
17. The method of claim 13 , wherein the patient has achieved clear or almost clear skin, as measured by an Investigator's Global Assessment score of 0 or 1, at week 16 of said once daily administration.
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 a human patient having moderate to severe atopic dermatitis, comprising orally administering once daily to the patient 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 the method results in an Eczema Area and Severity Index (EASI) 100 at 16 weeks after the first daily administration.
20. The method of claim 19 , wherein the patient is an adult.
21. The method of claim 20 , wherein the patient had inadequately responded to treatment with topical corticosteroids or topical calcineurin inhibitors.
22. The method of claim 19 , wherein the method further comprises administering a topical corticosteroid to the patient.
23. The method of claim 19 , wherein the patient has achieved clear or almost clear skin, as measured by an Investigator9s Global Assessment score of 0 or 1, at week 16 of said once daily administration.
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.