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 - 21 . (canceled)
22 . A method of treating congenital adrenal hyperplasia (CAH), the method comprising administering to a subject 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), and wherein the CRF 1 receptor antagonist is administered in the form of a capsule.
23 . The method of claim 22 , wherein the congenital adrenal hyperplasia is due to 21-hydroxylase deficiency.
24 . The method of claim 22 , wherein the administration results in a reduction in the subject's level of ACTH.
25 . The method of claim 22 , wherein the administration results in a reduction in the subject's level of 17-OHP.
26 . The method of claim 22 , wherein the administration results in a reduction in the subject's level of androgens.
27 . The method of claim 26 , wherein the administration results in a reduction in the subject's level of androstenedione.
28 . The method of claim 22 , wherein excess androgen levels are normalized.
29 . The method of claim 22 , wherein androstenedione levels are controlled.
30 . The method of claim 22 , wherein the subject is an adult.
31 . The method of claim 22 , wherein the subject is a pediatric subject.
32 . The method of claim 22 , wherein a single dosage of the CRF 1 receptor antagonist is about 50 mg.
33 . The method of claim 22 , wherein a single dosage of the CRF 1 receptor antagonist is about 100 mg.
34 . The method of claim 22 , wherein the CRF 1 receptor antagonist is administered at bedtime.
35 . The method of claim 22 , wherein the CRF 1 receptor antagonist is administered prior to sleep.
36 . The method of claim 22 , wherein the CRF 1 receptor antagonist is administered at nighttime.
37 . The method of claim 22 , wherein the CRF 1 receptor antagonist is administered before the expected circadian release of ACTH.
38 . The method of claim 22 , wherein the CRF 1 receptor antagonist is administered about 2-4 hours before the expected circadian release of ACTH.
39 . The method of claim 22 , wherein the CRF 1 receptor antagonist is administered about 3-5 hours before the expected circadian release of ACTH.
40 . The method of claim 22 , wherein the CRF 1 receptor antagonist is administered about 3-4 hours before the expected circadian release of ACTH.
41 . The method of claim 37 , wherein the expected circadian release of ACTH is between 1 and 2 A.M.
42 . The method of claim 22 , wherein the subject is also administered a glucocorticoid.
43 . The method of claim 42 , wherein the glucocorticoid is hydrocortisone, dexamethasone, and/or prednisone.
44 . The method of claim 42 , wherein the dose of the glucocorticoid is decreased by 10% or more from the recommended daily dose of said glucocorticoid for the subject.
45 . The method of claim 42 , wherein the dose of the glucocorticoid is decreased by 15% or more from the recommended daily dose of said glucocorticoid for the subject.
46 . The method of claim 42 , wherein the dose of the glucocorticoid is decreased by 20% or more from the recommended daily dose of said glucocorticoid for the subject.
47 . The method of claim 42 , wherein the dose of the glucocorticoid is decreased by 30% or more from the recommended daily dose of said glucocorticoid for the subject.
48 . The method of claim 42 , wherein the dose of the glucocorticoid is decreased by 40% or more from the recommended daily dose of said glucocorticoid for the subject. dose.
49 . The method of claim 42 , wherein the dose of the glucocorticoid is a physiologic
50 . The method of claim 44 , wherein excess androgen levels are normalized.
51 . The method of claim 49 , wherein androstenedione levels are controlled.