Compositions comprising an RNA polymerase inhibitor and cyclodextrin for treating viral infections

Patent metadata

Field	Value
Publication number	US-11266681-B2
Application number	US-202016865209-A
Country	US
Kind code	B2
Filing date	May 1, 2020
Priority date	Jul 11, 2017
Publication date	Mar 8, 2022
Grant date	Mar 8, 2022

Abstract

The present disclosure provides a composition comprising Compound 1, or a pharmaceutically acceptable salt thereof, cyclodextrin, and, optionally, pH adjusting agents.

First claim

What is claimed is:

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

Assignees

• Gilead Sciences Inc

Inventors

• Larson Nate
• Strickley Robert G

Classifications

• A61P31/14

  for RNA viruses · CPC title

• A61P31/12

  Antivirals · CPC title

• A61K9/19

  lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)} · CPC title

• A61K9/0019 Primary

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61K31/683

  Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols · CPC title