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 a 17-hydroxyprogesterone (17-OHP) 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 CAH is classic CAH.
10 . The method of claim 1 , wherein CAH is non-classic CAH.
11 . The method of claim 1 , wherein the 17-OHP level in a human is reduced by at least 15% from baseline.
12 . The method of claim 1 , wherein the 17-OHP level in a human is reduced by at least 20% from baseline.
13 . The method of claim 1 , wherein the 17-OHP level in a human is reduced by at least 25% from baseline.
14 . The method of claim 1 , wherein the 17-OHP level in a human is reduced by at least 10% from baseline and is maintained at a reduced level post 24 hours.
15 . The method of claim 1 , wherein the 17-OHP level in a human is reduced by at least 10% from baseline and is maintained at a reduced level post 4 weeks.
16 . The method of claim 1 , wherein the 17-OHP level in a human is reduced by at least 10% from baseline and is maintained at a reduced level post 6 weeks.
17 . The method of claim 1 , further comprising administering a glucocorticoid (GC).
18 . The method of claim 17 , wherein Compound 1 or a pharmaceutically acceptable salt thereof is administered 4 hours prior to sleeping.
19 . The method of claim 17 , wherein the GC is administered concurrently or sequentially within 2 hours of the administration of Compound 1 or a pharmaceutically acceptable salt thereof.
20 . The method of claim 17 , wherein the glucocorticoid is selected from beclomethasone, betamethasone, budesonide, cortisone, dexamethasone, hydrocortisone, methylprednisolone, prednisolone, prednisone, and triamcinolone.
21 . The method of claim 20 , wherein the glucocorticoid is hydrocortisone.