Corticotropin releasing factor receptor antagonists
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).
1. A method of treating congenital adrenal hyperplasia (CAH) in a human comprising administering to the human a therapeutically-effective amount of a CRF 1 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 CRF 1 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 CRF 1 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 CRF 1 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 CRF 1 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 μm and about 20 μm.
7. The method of claim 1 , wherein said CRF 1 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.
11. A method of treating congenital adrenal hyperplasia in a human comprising administering to the human a therapeutically-effective amount of a CRF 1 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 CRF 1 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 CRF 1 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 CRF 1 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 CRF 1 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 μm and about 20 μm.
17. The method of claim 11 , wherein said CRF 1 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.
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.
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.
23. The method of either claim 1 or claim 11 , further comprising administering a glucocorticoid (GC).
24. The method of claim 23 , wherein said CRF 1 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 CRF 1 receptor antagonist or a pharmaceutically acceptable salt thereof.