Formulations for treatment of dry eye disease

Patent metadata

Field	Value
Publication number	US-11197821-B2
Application number	US-201916582720-A
Country	US
Kind code	B2
Filing date	Sep 25, 2019
Priority date	Sep 25, 2018
Publication date	Dec 14, 2021
Grant date	Dec 14, 2021

Abstract

The present invention provides a reproxalap ophthalmic solution, and methods of using the same for treating dry eye disease.

First claim

We claim:

1. A method of treating dry eye disease in a subject, comprising topically administering to an eye of a subject with dry eye disease a therapeutically effective amount of an ophthalmic solution comprising reproxalap, or a pharmaceutically acceptable salt thereof, at about 0.2% w/v to about 0.3% w/v, and a pharmaceutically acceptable excipient comprising a cyclodextrin, wherein the cyclodextrin is sulfobutylether-β-cyclodextrin or hydroxypropyl-β-cyclodextrin, or a pharmaceutically acceptable salt thereof; wherein the reproxalap and cyclodextrin are present in a ratio of about 1:2, about 1:3, about 1:4, or about 1:5 on a mole:mole basis; and wherein the ophthalmic solution is topically administered to the eye with dry eye disease four times a day in an initiation phase or exacerbation phase followed by three times a day, twice a day, once a day, or as needed in a maintenance phase.

2. The method of claim 1 , wherein the ophthalmic solution is topically administered to the eye with dry eye disease three times a day in the maintenance phase.

3. The method of claim 1 , wherein the ophthalmic solution is topically administered to the eye with dry eye disease two times a day in the maintenance phase.

4. The method of claim 1 , wherein the ophthalmic solution is topically administered to the eye with dry eye disease once a day in the maintenance phase.

5. The method of claim 1 , wherein the treatment is for at least 12 weeks.

6. The method of claim 1 , wherein the ophthalmic solution is topically administered to the eye with dry eye disease four times a day for about 2 to 6 weeks in an initiation phase or exacerbation phase followed by administration three times a day, two times a day, once a day, or as needed in a maintenance phase.

7. The method of claim 6 , wherein the maintenance phase is administration three times a day, two times a day, once a day, or as needed for about 6 to 10 weeks.

8. The method of claim 7 , wherein the maintenance phase is administration two times a day.

9. A method of treating dry eye disease in a subject, comprising:
topically administering to an eye of a subject with dry eye disease a therapeutically effective amount of an ophthalmic solution comprising reproxalap, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient comprising a cyclodextrin,
wherein the reproxalap is at about 0.2% w/v to about 0.3% w/v, and the cyclodextrin is sulfobutylether-β-cyclodextrin or hydroxypropyl-β-cyclodextrin, or a pharmaceutically acceptable salt thereof, wherein the reproxalap and cyclodextrin are present in a ratio of about 1:2, about 1:3, about 1:4, or about 1:5 on a mole:mole basis, and
wherein the ophthalmic solution is administered four times a day.

10. The method of claim 9 , wherein reproxalap is at about 0.25% w/v and the pharmaceutically acceptable excipient comprises sulfobutylether-β-cyclodextrin, wherein the sulfobutylether-β-cyclodextrin, or a pharmaceutically acceptable salt thereof of is at about 7% w/v.

11. The method of claim 9 , wherein reproxalap is at a concentration of 0.25% w/v and the pharmaceutically acceptable excipient comprises sulfobutylether-β-cyclodextrin, wherein the sulfobutylether-β-cyclodextrin, or a pharmaceutically acceptable salt thereof, is at about 11% w/v.

12. A method of treating dry eye disease in a subject, comprising topically administering to an eye of a subject with dry eye disease a therapeutically effective amount of an ophthalmic solution comprising reproxalap, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient comprising a cyclodextrin,
wherein the reproxalap is at about 0.2% w/v to about 0.3% w/v, and the cyclodextrin is sulfobutylether-β-cyclodextrin or hydroxypropyl-β-cyclodextrin, or a pharmaceutically acceptable salt thereof, wherein the reproxalap and cyclodextrin are present in a ratio of about 1:2, about 1:3, about 1:4, or about 1:5 on a mole:mole basis, and
wherein the ophthalmic solution is administered at least four times a day in an initiation phase or exacerbation phase, followed by three times a day, two times a day, once a day, or as needed in a maintenance phase.

13. The method of claim 12 , wherein the ophthalmic solution is administered two times a day in the maintenance phase.

14. The method of claim 12 , wherein reproxalap is at about 0.25% w/v and the pharmaceutically acceptable excipient comprises sulfobutylether-β-cyclodextrin, wherein the sulfobutylether-β-cyclodextrin, or a pharmaceutically acceptable salt thereof of, is at about 7% w/v.

15. The method of claim 12 , wherein reproxalap is at a concentration of 0.25% w/v and the pharmaceutically acceptable excipient comprises sulfobutylether-β-cyclodextrin, wherein the sulfobutylether-β-cyclodextrin, or a pharmaceutically acceptable salt thereof, is at about 11% w/v.

16. The method of claim 12 , wherein the ophthalmic solution is administered at a dose strength to achieve an early onset of effect.

17. The method of claim 16 , wherein the early onset effect is for dry eye symptoms of one or more of: ocular dryness, itchiness, tearing, burning, stinging, grittiness, cloudy vision, sensitivity to environment, and stringy ocular secretion.

18. The method of claim 16 , wherein the early onset of effect is for dry eye signs of one or more of: ocular vital staining, tear film break-up time, tear osmolarity, and tear volume.

19. The method of claim 1 , wherein the ophthalmic solution further comprises a tonicity agent consisting of about 0.2 to about 0.3% w/v sodium chloride, 0.07 to 0.09% sodium phosphate (dibasic), and 0.015% to 0.019% w/v sodium phosphate (monobasic); and the pH is about 7.3.

20. The method of claim 1 , wherein the reproxalap and cyclodextrin are present in a ratio of about 1:3 on a mole:mole basis.

21. The method of claim 1 , wherein the reproxalap and cyclodextrin are present in a ratio of about 1:4 on a mole:mole basis.

22. The method of claim 1 , wherein reproxalap, or a pharmaceutically acceptable salt thereof, is at about 0.25% w/v, and the cyclodextrin is sulfobutylether-β-cyclodextrin at about 7% w/v.

23. The method of claim 1 , wherein reproxalap, or a pharmaceutically acceptable salt thereof, is at about 0.25% w/v, and the cyclodextrin is sulfobutylether-β-cyclodextrin at about 11% w/v.

24. The method of claim 19 , wherein the reproxalap and cyclodextrin are present in a ratio of about 1:4 on a mole:mole basis.

Assignees

• Aldeyra Therapeutics Inc

Inventors

• Clark David
• Brady Todd
• Macdonald Susan
• Machatha Stephen Gitu

Classifications

• A61K31/47 Primary

  Quinolines; Isoquinolines · CPC title

• A61K9/08

  Solutions {(composition of solutions A61K47/00)} · CPC title

• A61K47/40

  Cyclodextrins; Derivatives thereof · CPC title

• A61P27/04

  Artificial tears; Irrigation solutions · CPC title

• A61K9/0048 Primary

  Eye, e.g. artificial tears · CPC title