Dosing regimens of celgosivir for the treatment of dengue

Patent metadata

Field	Value
Publication number	US-9763921-B2
Application number	US-201414772873-A
Country	US
Kind code	B2
Filing date	Mar 14, 2014
Priority date	Mar 15, 2013
Publication date	Sep 19, 2017
Grant date	Sep 19, 2017

Abstract

Methods of treating a dengue virus (DENV) infection in a human subject, comprising administering to the human subject a compound of Formula (I), or pharmaceutical composition comprising a compound of Formula (I): A compound of Formula (I) can be administered within onset of fever to 72 hours of fever onset due to dengue infection and then every 6 to 12 hours until there is an improvement in the infection or between from about 1 day to about 10 days. The methods of the invention can be used to treat primary and secondary DENV1-4 viral infections.

First claim

What is claimed is:

1. A method of treating a dengue virus (DENV) infection in a human subject, comprising:
a) administering to the human subject an initial dose of about 100 to about 600 mg of a compound of Formula (II), or a pharmaceutical composition comprising a compound of Formula (II), within from about onset of fever to about 72 hours of fever onset due to dengue infection; and
b) administering to the human subject a dose of about 25 to about 300 mg of a compound of Formula (II), or a pharmaceutical composition comprising a compound of Formula (II), at intervals of from about 6 to about 12 hours until there is an improvement in the infection or between from about 1 day to about 10 days, Formula (II), having the following structure,

or a pharmaceutically acceptable salt thereof.

2. A method of treating a secondary dengue infection in a human subject, comprising:
a) administering to the human subject an initial dose of about 100 to about 600 mg of a compound of Formula (II), or a pharmaceutical composition comprising a compound of Formula (II), within from about onset of fever to about 72 hours of fever onset due to dengue infection; and
b) administering to the human subject a dose of about 25 to about 300 mg of a compound of Formula (II), or a pharmaceutical composition comprising a compound of Formula (II), at intervals of from about 6 to about 12 hours until there is an improvement in the infection or between from about 1 day to about 10 days, Formula (II) having the following structure,

or a pharmaceutically acceptable salt thereof.

3. A method of treating a dengue virus (DENV) infection in a human subject, comprising:
a) administering orally to the human subject an initial dose of about 100 to about 600 mg of a compound of Formula (II), or a pharmaceutical composition comprising a compound of Formula (II), within from about onset of fever to about 72 hours of fever onset due to dengue infection; and
b) administering orally to the human subject a dose of about 25 to about 300 mg of a compound of Formula (II), or a pharmaceutical composition comprising a compound of Formula (II), at intervals of from about 6 to about 12 hours until there is an improvement in the infection or between from about 1 day to about 10 days, Formula (II) having the following structure,

or a pharmaceutically acceptable salt thereof.

4. The method of claim 1 or claim 2 , wherein the human subject is an adult or a child.

5. The method of claim 1 , wherein the compound of Formula (II) is converted to castanospermine after administration to a human subject.

6. The method of claim 1 , wherein a steady state Cmin serum or plasma concentration of between about 0.05 and about 2.0 microgram/mL of castanospermine in an adult or child human subject is attained after treatment.

7. The method of claim 1 , wherein a steady state Cmin serum or plasma concentration of between about 1.0 and about 2.0 microgram/mL of castanospermine in an adult or child human subject is attained after treatment.

8. The method of claim 1 , wherein a steady state Cmin serum or plasma concentration of between about 1.0 and about 1.5 microgram/mL of castanospermine in an adult or child human subject is attained after treatment.

9. The method of claim 1 , wherein a steady state Cmin serum or plasma concentration of between about 1.5 and about 2.0 microgram/mL of castanospermine in an adult or child human subject is attained after treatment.

10. The method of claim 1 , wherein a steady state Cmin serum or plasma concentration of between about 1.25 and about 1.75 microgram/mL of castanospermine in an adult or child human subject is attained after treatment.

11. The method of claim 1 , wherein dengue viral infection comprises at least one dengue virus selected from DENV1, DENV2, DENV3 and DENV4.

12. The method of claim 1 , wherein the dengue viral infection is secondary dengue infection.

13. The method of claim 1 , wherein the human subject to be treated is positive prior to treatment for a dengue infection using a NS1 strip assay or quantitative PCR.

14. The method of claim 1 , wherein the virological log reduction in treated human subjects is at least 50% greater than untreated or placebo-treated groups.

15. The method of claim 1 , wherein administering the compound, or the pharmaceutical composition, achieves a steady state Cmin serum or plasma concentration of between about 0.05 and about 2.0 microgram/mL of castanospermine.

16. The method of claim 1 , wherein administering the compound, or the pharmaceutical composition, achieves a steady state Cmin serum or plasma concentration of between about 1.0 and about 2.0 microgram/mL of castanospermine.

17. The method of claim 1 , wherein administering the compound, or the pharmaceutical composition, achieves a steady state Cm in serum or plasma concentration of between about 1.0 and about 1.5 microgram/mL of castanospermine.

18. The method of claim 1 , wherein administering the compound, or the pharmaceutical composition, achieves a steady state Cmin serum or plasma concentration of between about 1.5 and about 2.0 microgram/mL of castanospermine.

19. The method of claim 1 , wherein administering the compound, or the pharmaceutical composition, achieves a steady state Cmin serum or plasma concentration of between about 1.25 and about 1.75 microgram/mL of castanospermine.

20. The method of claim 1 , wherein the compound, or the pharmaceutical composition, is administered intravenously, orally, rectally, or sublingually.

21. The method of claim 1 , wherein the human subject is administered an initial dose of 150 mg and a dose of 100 mg is thereafter administered to the human subject every 6 hours, 8 hours, or 12 hours for about 1 day, about 2 days, or about 5 days.

22. The method of claim 1 , wherein the human subject is administered an initial dose of 150 mg and a dose of 150 mg is thereafter administered to the human subject every 6 hours for about 1 day, about 2 days, or about 5 days.

23. The method of claim 1 , wherein the human subject is administered an initial dose of 150 mg and a dose of 150 mg is thereafter administered to the human subject every 8 hours for about 1 day, about 2 days, or about 5 days.

24. The method of claim 1 , wherein the human subject is administered an initial dose of 150 mg and a dose of 150 mg is thereafter administered to the human subject every 12 hours for about 1 day, about 2 days, or about 5 days.

25. The method of claim 1 , wherein the human subject is administered an initial dose of 150 mg and a dose of 200 mg is thereafter administered to the human subject every 6 hours, 8 hours, or 12 hours for about 1 day, about 2 days, or about 5 days.

26. The method of claim 1 , wherein the human subject is administered an initial dose of 200 mg and a dose of 100 mg is thereafter administered to the human subject every 6 hours, 8 hours, or 12 hours for about 1 day, about 2 days, or about 5 days.

27. The method of claim 1 , wherein the human subject is administered an initial dose of 200 mg and a dose of 150 mg is thereafter administered

Assignees

• 60 Degrees Pharmaceuticals Llc
• Nat Univ Singapore
• Singapore Health Serv Pte Ltd
• 60 Degrees Pharmaceuticals Llc
• Singapore Health Serv Pte Ltd

Inventors

• Dow Geoffrey S
• Vasudevan Subhash
• Reid Mark
• Morrish Glynn
• Sung Cynthia
• Rathore Abhay
• Watanabe Satoru
• Ooi Eng Eong
• Low Jenny

Classifications

• A61P31/14

  for RNA viruses · CPC title

• A61K31/437 Primary

  the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline · CPC title

• Y02A50/30

  Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change · CPC title