Treatment of congenital adrenal hyperplasia
CRF 1 receptor antagonists have the potential to directly inhibit ACTH release in patients with CAH and thereby allow normalization of androgen production while using lower, more physiologic doses of hydrocortisone, and thus reducing treatment-associated side effects.
1. A method of treating Congenital Adrenal Hyperplasia (CAH), said method comprising administering to a subject in need thereof already being treated with a glucocortocoid, an effective amount of a CRF 1 receptor antagonist, wherein the CRF 1 receptor antagonist is 4-(2-chloro-4-methoxy-5-methylphenyl)-N-[(1S)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-N-(2-propyn-1-yl)-2-thiazolamine (SSR-125543), or a pharmaceutically acceptable salt thereof.
2. The method of claim 1 , wherein the glucocorticoid is hydrocortisone.
3. The method of claim 1 , wherein the glucocorticoid is prednisone.
4. The method of claim 1 , wherein the glucocorticoid is prednisolone.
5. The method of claim 1 , wherein the glucocorticoid is dexamethasone.
6. The method of claim 1 , further comprising administering a salt-wasting, mineralocorticoid to the subject.
7. The method of claim 6 , wherein the salt-wasting, mineralocorticoid is fludrocortisone.
8. The method of claim 1 , wherein the dose of the glucocorticoid is decreased by 10% or more following administration of the CRF 1 receptor antagonist.
9. The method of claim 1 , wherein the dose of the glucocorticoid is decreased by 15% or more following administration of the CRF 1 receptor antagonist.
10. The method of claim 1 , wherein the dose of the glucocorticoid is decreased by 20% or more following administration of the CRF 1 receptor antagonist.
11. The method of claim 1 , wherein the dose of the glucocorticoid is decreased by 30% or more following administration of the CRF 1 receptor antagonist.
12. The method of claim 1 , wherein the dose of the glucocorticoid is decreased by 40% or more following administration of the CRF 1 receptor antagonist.
13. The method of claim 1 , wherein the dose of the glucocorticoid is decreased by 50% or more following administration of the CRF 1 receptor antagonist.
14. The method of claim 1 , wherein the CAH is classical CAH.
15. The method of claim 1 , wherein the CAH is caused by 21-α hydroxylase deficiency.
16. The method of claim 1 , wherein the CAH is caused by 11β-hydroxylase deficiency.
17. The method of claim 1 , wherein the subject has a mutation in the CYP21A2 gene located on chromosome 6p21.
18. The method of claim 1 , wherein the subject does not have a mutation of the 11β-hydroxylase gene CYP11B1 (11β-OH CAH).
19. The method of claim 1 , wherein the CRF 1 receptor antagonist is administered at bedtime.
20. The method of claim 1 , wherein the CRF 1 receptor antagonist is 4-(2-chloro-4-methoxy-5-methylphenyl)-N-[(1S)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-N-(2-propyn-1-yl)-2-thiazolamine (S SR-125543).
21. The method of claim 1 , wherein 4-(2-chloro-4-methoxy-5-methylphenyl)-N-[(1S)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-N-(2-propyn-1-yl)-2-thiazolamine (SSR-125543), or a pharmaceutically acceptable salt thereof, is administered in the form of a liquid formulation.
22. The method of claim 1 , wherein 4-(2-chloro-4-methoxy-5-methylphenyl)-N-[(1S)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-N-(2-propyn-1-yl)-2-thiazolamine (SSR-125543), or a pharmaceutically acceptable salt thereof, is administered in the form of a solid formulation.
23. The method of claim 1 , wherein 4-(2-chloro-4-methoxy-5-methylphenyl)-N-[(1S)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-N-(2-propyn-1-yl)-2-thiazolamine (SSR-125543), or a pharmaceutically acceptable salt thereof, is administered in the form of a semi-solid formulation.
24. The method of claim 1 , wherein 4-(2-chloro-4-methoxy-5-methylphenyl)-N-[(1S)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-N-(2-propyn-1-yl)-2-thiazolamine (SSR-125543), or a pharmaceutically acceptable salt thereof, is administered in the form of a tablet, powder, granule or capsule.
25. The method of claim 24 , wherein 4-(2-chloro-4-methoxy-5-methylphenyl)-N-[(1S)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-N-(2-propyn-1-yl)-2-thiazolamine (SSR-125543), or a pharmaceutically acceptable salt thereof, is administered in the form of a capsule.
26. The method of claim 1 , wherein the subject is an adult.
27. The method of claim 1 , wherein the subject is a child.
28. The method of claim 1 , wherein the subject is a female.