Corticotropin releasing factor receptor antagonists

• US 10,849,908 B2
• Filed: 04/18/2019
• Issued: 12/01/2020
• Est. Priority Date: 08/14/2017
• Status: Active Grant

• Current Assignee: Spruce Biosciences, Inc.
• Original Assignee: Spruce Biosciences, Inc.
• Inventors: Howerton, Alexis, Gerber, Hal, Huang, Michael
• Primary Examiner(s): Roney, Celeste A
• Application Number:
  US16/388,620
• Publication Number:
  US 20190262349A1
• Time in Patent Office: 593 Days
• Field of Search: None
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 9/14 Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51
• CPC Class Codes: A61K 9/48 Preparations in capsules, e.g. of gelatin, of chocolate A61K9/0004 takes precedence; bite capsules A61K9/0056
• CPC Class Codes: A61K 9/4825 Proteins, e.g. gelatin gelatin capsule shells with substantial amounts of other macromolecular substances A61K9/4816
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 5/24 of the sex hormones
• CPC Class Codes: A61P 5/38 of the suprarenal hormones
• CPC Class Codes: C07D 487/04 Ortho-condensed systems

Abstract

The present invention provides novel pharmaceutical compositions comprising -(4-Chloro-2-(morpholin-4-yl)thiazol-5-yl)-7-(1-ethylpropyl)-2,5-dimethylpyrazolo(1,5-a)pyrimidine and methods of using the same for the treatment of Congenital adrenal hyperplasia (CAH).

Claims

1. A method of treating congenital adrenal hyperplasia (CAH) in a human comprising administering to the human a therapeutically-effective amount of a CRF₁ receptor antagonist or a pharmaceutically acceptable salt thereof, wherein an adrenocorticotropic hormone (ACTH) level in the human is reduced by at least 10% from baseline.

2. The method of claim 1, wherein said CRF₁ receptor antagonist or a pharmaceutically acceptable salt thereof is administered at a dose between about 50 mg/day and about 1600 mg/day.

3. The method of claim 1, wherein said CRF₁ receptor antagonist or a pharmaceutically acceptable salt thereof is administered at a dose between about 100 mg/day and about 600 mg/day.

4. The method of claim 1, wherein said CRF₁ receptor antagonist or a pharmaceutically acceptable salt thereof is administered at a dose of about 200 mg/day.

5. The method of claim 1, wherein said CRF₁ receptor antagonist or a pharmaceutically acceptable salt thereof is in the form of microparticles.

6. The method of claim 5, wherein the average size of said microparticles is between about 1 μ

m and about 20 μ

m.

7. The method of claim 1, wherein said CRF₁ receptor antagonist or a pharmaceutically acceptable salt thereof is in the form of a pharmaceutical composition.

8. The method of claim 7, wherein said pharmaceutical composition is in the form of a capsule or a tablet.

9. The method of claim 1, wherein CAH is classic CAH.

10. The method of claim 1, wherein CAH is non-classic CAH.

21. The method of claim 1, wherein said ACTH level in a human is reduced by at least 10% from baseline and is maintained at a reduced level post 24 hours.

23. The method of either claim 1 or claim 11, further comprising administering a glucocorticoid (GC).

24. The method of claim 23, wherein said CRF₁ receptor antagonist or a pharmaceutically acceptable salt thereof is administered 4 hours prior to sleeping.

25. The method of claim 23, wherein said GC is administered concurrently or sequentially within 2 hours of said administration of said CRF₁ receptor antagonist or a pharmaceutically acceptable salt thereof.

11. A method of treating congenital adrenal hyperplasia in a human comprising administering to the human a therapeutically-effective amount of a CRF₁ receptor antagonist or a pharmaceutically acceptable salt thereof, wherein a 17-hydroxyprogesterone (17-OHP) level is reduced in the human by at least about 10% from baseline.

12. The method of claim 11, wherein said CRF₁ receptor antagonist or a pharmaceutically acceptable salt thereof is administered at a dose between about 50 mg/day and about 1600 mg/day.

13. The method of claim 11, wherein said CRF₁ receptor antagonist or a pharmaceutically acceptable salt thereof is administered at a dose between about 100 mg/day and about 600 mg/day.

14. The method of claim 11, wherein said CRF₁ receptor antagonist or a pharmaceutically acceptable salt thereof is administered at a dose of about 200 mg/day.

15. The method of claim 11, wherein said CRF₁ receptor antagonist or a pharmaceutically acceptable salt thereof is in the form of microparticles.

16. The method of claim 15, wherein the average size of said microparticles is between about 1 μ

m and about 20 μ

m.

17. The method of claim 11, wherein said CRF₁ receptor antagonist or a pharmaceutically acceptable salt thereof is in the form of a pharmaceutical composition.

18. The method of claim 17, wherein said pharmaceutical composition is in the form of a capsule or a tablet.

19. The method of claim 11, wherein CAH is classic CAH.

20. The method of claim 11, wherein CAH is non-classic CAH.

22. The method of claim 11, wherein said 17-OHP level in a human is reduced by at least 10% from baseline and is maintained at a reduced level post 24 hours.