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 vasculitis), kits, methods of synthesis, and products-by-process. In various aspects, provided are methods for treating giant cell arteritis (GCA).
1 . A method of treating vasculitis in a human patient in need thereof, 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 oral corticosteroids.
4 . The method of claim 2 , wherein the method further comprises administering an oral corticosteroid to the patient.
5 . The method of claim 3 , wherein the method further comprises administering an oral corticosteroid to the patient.
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 giant cell arteritis (GCA) in a patient in need thereof, the method comprising orally administering once daily to the patient 15 mg 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 patient achieves remission of GCA 12 weeks following the first daily administration.
8 . The method of claim 7 , wherein the patient achieves sustained remission of GCA from 12 weeks following the first daily administration through 52 weeks following the first daily administration.
9 . The method of claim 7 , wherein the patient achieves complete remission of GCA 12 weeks following the first daily administration.
10 . The method of claim 9 , wherein the patient achieves sustained complete remission of GCA from 12 weeks following the first daily administration through 52 weeks following the first daily administration.
11 . A method of inducing remission of giant cell arteritis (GCA) in a patient in need thereof, the method comprising orally administering once daily to the patient 15 mg 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 patient achieves remission of GCA 12 weeks following the first daily administration.
12 . The method of claim 11 , wherein the patient achieves complete remission of GCA 12 weeks following the first daily administration.
13 . A method of inducing and sustaining remission of giant cell arteritis (GCA) in a patient in need thereof, the method comprising orally administering once daily to the patient 15 mg 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 patient achieves sustained remission of GCA from 12 weeks following the first daily administration through 52 weeks following the first daily administration.
14 . The method of claim 13 , wherein the patient achieves complete remission of GCA 12 weeks following the first daily administration.
15 . The method of claim 14 , wherein the patient achieves sustained complete remission of GCA from 12 weeks following the first daily administration through 52 weeks following the first daily administration.