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 in a human comprising administering to the human a therapeutically-effective amount of Compound 1:
or a pharmaceutically acceptable salt thereof, wherein an adrenocorticotropic hormone level in the human is reduced by at least 10% from baseline.
2. The method of claim 1 , wherein Compound 1 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 Compound 1 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 Compound 1 or a pharmaceutically acceptable salt thereof is administered at a dose of about 200 mg/day.
5. The method of claim 1 , wherein Compound 1 or a pharmaceutically acceptable salt thereof is in the form of microparticles.
6. The method of claim 5 , wherein the average size of the microparticles is between about 1 μm and about 20 μm.
7. The method of claim 1 , wherein Compound 1 or a pharmaceutically acceptable salt thereof is in the form of a pharmaceutical composition.
8. The method of claim 7 , wherein the pharmaceutical composition is in the form of a capsule or a tablet.
9. The method of claim 1 , wherein congenital adrenal hyperplasia is classic congenital adrenal hyperplasia.
10. The method of claim 1 , wherein congenital adrenal hyperplasia is non-classic congenital adrenal hyperplasia.
11. The method of claim 1 , further comprising administering a glucocorticoid.
12. The method of claim 11 , wherein Compound 1 or a pharmaceutically acceptable salt thereof is administered 4 hours prior to sleeping.
13. The method of claim 11 , wherein the glucocorticoid is administered concurrently or sequentially within 2 hours of said administration of Compound 1 or a pharmaceutically acceptable salt thereof.
14. The method of claim 1 , wherein the adrenocorticotropic hormone level in a human is maintained at a reduced level post 24 hours.
15. The method of claim 1 , wherein the adrenocorticotropic hormone level in a human is reduced by at least 15% from baseline.
16. The method of claim 1 , wherein the adrenocorticotropic hormone level in a human is reduced by at least 20% from baseline.
17. The method of claim 1 , wherein the adrenocorticotropic hormone level in a human is reduced by at least 25% from baseline.
18. The method of claim 1 , wherein the adrenocorticotropic hormone level in a human is reduced by at least 10% from baseline and is maintained at a reduced level post 4 weeks.
19. The method of claim 1 , wherein the adrenocorticotropic hormone level in a human is reduced by at least 10% from baseline and is maintained at a reduced level post 6 weeks.
20. The method of claim 11 , wherein the glucocorticoid is selected from beclomethasone, betamethasone, budesonide, cortisone, dexamethasone, hydrocortisone, methylprednisolone, prednisolone, prednisone, and triamcinolone.
21. The method of claim 11 , wherein the glucocorticoid is hydrocortisone.