Processes for the preparation of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]-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-(3Himidazo[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 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.
3. The method of claim 2 , wherein the adult 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. A method of treating a human patient having moderate to severe atopic dermatitis, 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 Eczema Area and Severity Index (EASI) 75 at 16 weeks after the first daily administration.
7. The method of claim 6 , wherein the patient is an adult.
8. The method of claim 7 , wherein the adult patient had inadequately responded to treatment with topical corticosteroids or topical calcineurin inhibitors.
9. The method of claim 6 , wherein the method further comprises administering a topical corticosteroid to the patient.
10. The method of claim 6 , 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.
11. A method of treating a human patient having moderate to severe atopic dermatitis, 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 Eczema Area and Severity Index (EASI) 90 at 16 weeks after the first daily administration.
12. The method of claim 11 , wherein the patient is an adult.
13. The method of claim 12 , wherein the adult patient had inadequately responded to treatment with topical corticosteroids or topical calcineurin inhibitors.
14. The method of claim 13 , wherein the method further comprises administering a topical corticosteroid to the patient.
15. The method of claim 11 , 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.
16. A method of treating a human patient having moderate to severe atopic dermatitis, 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 Eczema Area and Severity Index (EAST) 100 at 16 weeks after the first daily administration.
17. The method of claim 16 , wherein the patient is an adult.
18. The method of claim 17 , wherein the adult patient had inadequately responded to treatment with topical corticosteroids or topical calcineurin inhibitors.
19. The method of claim 18 , wherein the method further comprises administering a topical corticosteroid to the patient.
20. The method of claim 16 , 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.