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 pharmaceutical compositions 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 corresponding methods of treating psoriatic arthritis.
1. A method of treating a human patient having active psoriatic arthritis, 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 methotrexate.
5. The method of claim 1 , wherein the patient has had an inadequate response or intolerance to an anti-TNF biologic agent.
6. A method of treating a human patient having active psoriatic arthritis, 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 a ACR70 response at 12 weeks after the first daily administration.
7. The method of claim 6 , wherein the patient is an adult patient.
8. The method of claim 6 , wherein the patient has had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs.
9. The method of claim 6 , wherein the patient has had an inadequate response or intolerance to methotrexate.
10. The method of claim 6 , wherein the patient has had an inadequate response or intolerance to an anti-TNF biologic agent.
11. A method of treating a human patient suffering from active psoriatic arthritis that is statistically significantly superior to placebo, comprising orally administering once daily to the patient a dose of upadacitinib sufficient to deliver 15 mg of upadacitinib freebase equivalent, wherein when the method is used to treat a population of human patients suffering from active psoriatic arthritis, a statistically significantly greater percentage of patients achieve an ACR70 response at 12 weeks from administration of the first daily dose compared to a control group of human patients treated with placebo.
12. The method of claim 11 , wherein the patient is an adult patient.
13. The method of claim 11 , wherein the patient has had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs.
14. The method of claim 11 , wherein the patient has had an inadequate response or intolerance to methotrexate.
15. The method of claim 11 , wherein the patient has had an inadequate response or intolerance to an anti-TNF biologic agent.
16. The method of claim 11 , wherein the statistically significantly greater percentage of patients achieving an ACR70 response rate has a p value of less than 0.001.
17. A method of treating human patients suffering from active psoriatic arthritis that is statistically significantly superior to placebo, comprising orally administering once daily to each of the patients a dose of upadacitinib sufficient to deliver 15 mg of upadacitinib freebase equivalent, wherein the method results in a statistically significantly greater percentage of the patients achieving an ACR70 response at 12 weeks from administration of the first daily dose compared to a control group of human patients treated with placebo.
18. The method of claim 17 , wherein the patients are adult patients.
19. The method of claim 17 , wherein the patients have had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs.
20. The method of claim 17 , wherein the patients have had an inadequate response or intolerance to methotrexate.
21. The method of claim 17 , wherein the patients have had an inadequate response or intolerance to an anti-TNF biologic agent.
22. The method of claim 17 , wherein the statistically significantly greater percentage of patients achieving an ACR70 response rate has a p value of less than 0.001.