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-carb oxamide 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 atopic dermatitis), kits, methods of synthesis, and products-by-process.
1. A method for reducing the extent and severity of atopic eczema by at least 90% in a human patient having moderate to severe atopic dermatitis, comprising orally administering once daily to the patient in need thereof 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 patient has achieved at least an Eczema Area and Severity Index (EAST) 90 at week 16 of said once daily administration.
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 achieving clear or almost clear skin in a human patient having moderate to severe atopic dermatitis, comprising orally administering once daily to the patient in need thereof 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 patient has achieved an Investigator's Global Assessment score of 0 or 1 at week 16 of said once 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.