Compositions comprising an RNA polymerase inhibitor and cyclodextrin for treating viral infections
The present disclosure provides a composition comprising Compound 1, or a pharmaceutically acceptable salt thereof, cyclodextrin, and, optionally, pH adjusting agents.
1. A method of treating a viral infection in a human in need thereof, the method comprising
(a) reconstituting with safe water for injection a lyophilized pharmaceutical composition comprising:
(i) Compound 1,
or a pharmaceutically acceptable salt thereof, in an amount of from 1% to 10% w/w, and
(ii) cyclodextrin in an amount of from 90% to 99% w/w, thereby forming a reconstituted pharmaceutical composition; and
(b) administering to the human a therapeutically effective amount of the reconstituted pharmaceutical composition;
wherein the viral infection is caused by an Arenaviridae virus, a Coronaviridae virus, a Filoviridae virus, or a Paramyxoviridae virus.
2. The method of claim 1 , wherein the lyophilized pharmaceutical composition comprises:
(i) the Compound 1 in an amount of from 1% to 5% w/w; and
(ii) the cyclodextrin in an amount of from 95% to 99% w/w.
3. The method of claim 2 , wherein the cyclodextrin is sulfobutylalkylether-beta-cyclodextrin, betadex-sulfobutylether sodium, or hydroxypropyl-beta-cyclodextrin.
4. The method of claim 3 , wherein the cyclodextrin is betadex-sulfobutylether sodium.
5. The method of claim 1 , wherein the lyophilized pharmaceutical composition comprises:
(i) the Compound 1 in an amount of from 2% to 4% w/w; and
(ii) the cyclodextrin in an amount of from 96% to 98% w/w.
6. The method of claim 5 , wherein the cyclodextrin is sulfobutylalkylether-beta-cyclodextrin, betadex-sulfobutylether sodium, or hydroxypropyl-beta-cyclodextrin.
7. The method of claim 6 , wherein the cyclodextrin is betadex-sulfobutylether sodium.
8. The method of claim 1 , wherein the lyophilized pharmaceutical composition comprises:
(i) the Compound 1 in an amount of from 3% to 3.5% w/w; and
(ii) the cyclodextrin in an amount of from 96.5% to 97% w/w.
9. The method of claim 8 , wherein the cyclodextrin is betadex-sulfobutylether sodium.
10. The method of claim 1 , wherein the lyophilized pharmaceutical composition comprises the Compound 1 in an amount of from 50 mg to 250 mg.
11. The method of claim 10 , wherein the lyophilized pharmaceutical composition comprises the Compound 1 in an amount of 100 mg.
12. The method of claim 10 , wherein the lyophilized pharmaceutical composition comprises the Compound 1 in an amount of 200 mg.
13. The method of claim 1 , wherein the cyclodextrin is a beta-cyclodextrin.
14. The method of claim 13 , wherein the beta-cyclodextrin is sulfobutylalkylether-beta-cyclodextrin, betadex-sulfobutylether sodium, or hydroxypropyl-beta-cyclodextrin.
15. The method of claim 14 , wherein the cyclodextrin is betadex-sulfobutylether sodium.
16. The method of claim 1 , wherein the lyophilized pharmaceutical composition consists essentially of:
(i) the Compound 1 in an amount of 3.2% w/w, and
(ii) the cyclodextrin betadex-sulfobutylether sodium in an amount of 96.8% w/w.
17. The method of claim 1 , wherein the reconstituted pharmaceutical composition further comprises a pH adjusting agent.
18. The method of claim 17 , wherein the pH adjusting agent comprises HCl, NaOH, or a combination thereof.
19. The method of claim 17 , wherein the reconstituted pharmaceutical composition has a pH of from 3 to 4.
20. The method of claim 1 , wherein the reconstituted pharmaceutical composition comprises from 1 mg/mL to 10 mg/mL of the Compound 1.
21. The method of claim 20 , wherein the reconstituted pharmaceutical composition comprises from 4 mg/mL to 6 mg/mL of the Compound 1.
22. The method of claim 21 , wherein the reconstituted pharmaceutical composition comprises about 5 mg/mL of the Compound 1.
23. The method of claim 1 , wherein the reconstituted pharmaceutical composition comprises from 5% (w/v) to 50% (w/v) of the cyclodextrin.
24. The method of claim 23 , wherein the reconstituted pharmaceutical composition comprises from 10% (w/v) to 20% (w/v) of the cyclodextrin.
25. The method of claim 24 , wherein the reconstituted pharmaceutical composition comprises about 15% (w/v) of the cyclodextrin.
26. The method of claim 1 , wherein the viral infection is caused by a Coronaviridae virus.
27. The method of claim 1 , wherein the administering further comprises one or more additional therapeutic agents.
28. A method of treating a viral infection in a human in need thereof, the method comprising administering to the human a therapeutically effective amount of a composition comprising a lyophilized pharmaceutical composition, wherein the lyophilized pharmaceutical composition comprises:
(i) Compound 1,
or a pharmaceutically acceptable salt thereof, in an amount of from 1% to 10% w/w; and
(ii) cyclodextrin in an amount of from 90% to 99% w/w;
wherein the viral infection is caused by an Arenaviridae virus, a Coronaviridae virus, a Filoviridae virus, or a Paramyxoviridae virus.
29. The method of claim 28 , wherein the lyophilized pharmaceutical composition comprises:
(i) the Compound 1 in an amount of from 1% to 5% w/w; and
(ii) the cyclodextrin in an amount of from 95% to 99% w/w.
30. The method of claim 29 , wherein the cyclodextrin is sulfobutylalkylether-beta-cyclodextrin, betadex-sulfobutylether sodium, or hydroxypropyl-beta-cyclodextrin.
31. The method of claim 30 , wherein the cyclodextrin is betadex-sulfobutylether sodium.
32. The method of claim 28 , wherein the lyophilized pharmaceutical composition comprises:
(i) the Compound 1 in an amount of from 2% to 4% w/w; and
(ii) the cyclodextrin in an amount of from 96% to 98% w/w.
33. The method of claim 32 , wherein the cyclodextrin is sulfobutylalkylether-beta-cyclodextrin, betadex-sulfobutylether sodium, or hydroxypropyl-beta-cyclodextrin.
34. The method of claim 33 , wherein the cyclodextrin is betadex-sulfobutylether sodium.
35. The method of claim 28 , wherein the lyophilized pharmaceutical composition comprises:
(i) the Compound 1 in an amount of from 3% to 3.5% w/w; and
(ii) the cyclodextrin in an amount of from 96.5% to 97% w/w.
36. The method of claim 35 , wherein the cyclodextrin is betadex-sulfobutylether sodium.
37. The method of claim 28 , wherein the lyophilized pharmaceutical composition comprises the Compound 1 in an amount of from 50 mg to 250 mg.
38. The method of claim 37 , wherein the lyophilized pharmaceutical composition comprises the Compound 1 in an amount of 100 mg.
39. The method of claim 37 , wherein the lyophilized pharmaceutical composition comprises the Compound 1 in an amount of 200 mg.
40. The method of claim 28 , wherein the cyclodextrin is a beta-cyclodextrin.
41. The method of claim 40 , wherein the beta-cyclodextrin is sulfobutylalkylether-beta-cyclodextrin, betadex-sulfobutylether sodium, or hydroxypropyl-beta-cyclodextrin.
42. The method of claim 41 , wherein the cyclodextrin is betadex-sulfobutylether sodium.
43. The method of claim 28 , wherein the lyophilized pharmaceutical composition consists essentially of:
(i) the Compound 1 in an amount of 3.2% w/w, and
(ii) the cyclodextrin betadex-sulfobutylether sodium in an amount of 96.8% w/w.
44. The method of claim 28 , wherein the viral infection is caused by a Coronaviridae virus.
45. The method of claim 28 , wherein the administering further comprises one or more additional therapeutic agents.