Pharmacology of visual cycle modulators

Patent metadata

Field	Value
Publication number	US-10471027-B2
Application number	US-83015510-A
Country	US
Kind code	B2
Filing date	Jul 2, 2010
Priority date	Jul 2, 2009
Publication date	Nov 12, 2019
Grant date	Nov 12, 2019

Abstract

Described herein are methods for the treatment of an ophthalmic disease or disorder comprising the administration of non-retinoid visual cycle modulators. Ophthalmic diseases and disorders which can be treated according to the methods provided herein include age-related macular degeneration (AMD), Stargardt's disease, glaucoma, and other disorders that adversely affect the retina.

First claim

What is claimed is:

1. A method of treating Stargardt's macular dystrophy, comprising administering daily a single oral dose of an amount from about 5 mg to about 10 mg of a non-retinoid compound (R)-3-amino-1-(3-(cyclohexylmethoxy)phenyl)propan-1-ol having the formula:

2. The method of claim 1 , wherein the normalized electroretinogram response is from about 5% to about 15%, from about 15% to about 25%, from about 25% to about 35%, or from about 35% to about 50%.

3. The method of claim 1 , wherein the normalized electroretinogram response is determined after about 12 hours to about 16 hours, after about 16 hours to about 20 hours, after about 20 hours to about 24 hours, after about 24 hours to about 30 hours, after about 30 hours to about 36 hours, after about 36 hours to about 42 hours, post administration of said non-retinoid compound.

4. The method of claim 1 , wherein administration of a single dose of the non-retinoid compound results in a greater normalized electroretinogram response on day 1 than on day 2.

5. The method of claim 1 , wherein administration of the non-retinoid compound results in a greater therapeutic response on day 2 than on day 1 after the administration of a single dose.

6. The method of claim 5 , wherein the therapeutic response is determined by electroretinography.

7. The method of claim 1 , wherein administration of the non-retinoid compound results in a normalized electroretinogram response of less than about 50% for a time period of about 4 hours to about 10 hours, about 10 hours to about 16 hours, about 16 hours to about 24 hours, or about 24 hours to about 36 hours after the plasma concentration of said non-retinoid compound has declined to 0.3 C max .

8. The method of claim 1 , wherein non-retinoid compound is administered in the morning, is administered upon waking from sleep, or is administered upon waking from sleep in the morning.

9. The method of claim 1 , wherein the amount administered is about 5 mg, about 7 mg, or about 10 mg of the non-retinoid compound.

10. The method of claim 1 , wherein the cone response amplitude of the electroretinogram remains within about 10%, within about 20%, or within about 30% of the pre-treatment amplitude.

11. The method of claim 1 , wherein the dosage of non-retinoid compound is adjusted to provide no noticeable deficiency in night vision.

12. The method of claim 1 , wherein the method results in no detectable effect on sensitivity in photopic conditions.

13. The method of claim 1 , wherein the non-retinoid compound is an in the form of a controlled-release solid dosage form.

14. The method of claim 13 , wherein administration of the controlled-release solid dosage form results in a plasma T max 12 hours post-administration.

15. The method of claim 1 , wherein non-retinoid compound is administered at a time other than the morning.

16. The method of claim 15 , wherein non-retinoid compound is administered during lunch or subsequent to lunch.

17. The method of claim 1 , wherein the administration of the non-retinoid compound results in a normalized electroretinogram response of less than about 50% for a time period of about 4 hours to about 36 hours after the plasma concentration of the compound has declined to 0.3 C max following administration.

18. The method of claim 1 , wherein the administration of the non-retinoid compound results in no noticeable loss in photopic vision.

19. The method of claim 1 , wherein the administration of the non-retinoid compound results in no noticeable deficiency in night vision.

Assignees

• Kubota Ryo
• Boman Nancy
• Bavik Claes
• Scott Ian L
• Acucela Inc

Inventors

• Kubota Ryo
• Boman Nancy
• Bavik Claes
• Scott Ian L

Classifications

• A61P9/10

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• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P31/18

  for HIV · CPC title

• A61P31/12

  Antivirals · CPC title