METHODS OF TREATING CONGENITAL ADRENAL HYPERPLASIA
Patients with congenital adrenal hyperplasia (CAH) need adequate care and treatment in order to lead normal lives. Hence, there is a need for new methods of treating CAH. This disclosure provides new compounds, salts, compositions and uses thereof in the treatment of CAH.
1 . A method of treating Congenital Adrenal Hyperplasia (CAH), comprising
administering a glucocorticoid or a pharmaceutically acceptable salt thereof, and a corticotropin-releasing factor type-1 (CRF1) antagonist to a subject in need thereof, wherein the CRF1 antagonist is SSR125543 or (S)-4-(2-chloro-4-methoxy-5-methylphenyl)-N-(2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl)-5-methyl-N-(prop-2-yn-1-yl)thiazol-2-amine, or a pharmaceutically acceptable salt thereof,
wherein when said subject has a level of 17-hydroxyprogesterone (17-OHP) that is less than two times an upper limit of a reference range of 17-OHP and a level of androstenedione (A4) that is less than two times an upper limit of a reference range of A4, a dose of said glucocorticoid or a pharmaceutically acceptable salt thereof is reduced compared to a dose of said glucocorticoid or a pharmaceutically acceptable salt thereof administered to a CAH patient that does not receive said CRF 1 antagonist or a pharmaceutically acceptable salt thereof, and
wherein the subject is in a fed state, and
wherein the subject is on a glucocorticoid regimen.
2 . The method of claim 1 , wherein the CRF1 antagonist is SSR125543, or a pharmaceutically acceptable salt thereof.
3 . The method of claim 1 , wherein the CRF 1 antagonist is (S)-4-(2-chloro-4-methoxy-5-methylphenyl)-N-(2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl)-5-methyl-N-(prop-2-yn-1-yl)thiazol-2-amine.
4 . The method of claim 1 , wherein the glucocorticoid is beclomethasone, betamethasone, budesonide, cortisone, dexamethasone, hydrocortisone, methylprednisolone, prednisolone, prednisone, or triamcinolone.
5 . The method of claim 1 , wherein the subject is on a glucocorticoid regimen of hydrocortisone.
6 . The method of claim 1 , wherein the subject is 4 years of age or older.
7 . The method of claim 1 , wherein the CRF 1 antagonist is orally administered twice daily.
8 . The method of claim 7 , wherein the CRF1 antagonist dose depends on the weight of the subject.
9 . The method of claim 8 , wherein the CRF1 antagonist is administered at 25 mg orally twice daily.
10 . The method of claim 8 , wherein the CRF 1 antagonist is administered at 50 mg orally twice daily.
11 . The method of claim 8 , wherein the CRF 1 antagonist is administered at 100 mg orally twice daily.
12 . The method of claim 8 , wherein the CRF1 antagonist is administered at 200 mg orally twice daily.
13 . The method of claim 1 , wherein administering the CRF1 antagonist reduces a concentration of 17-OHP, A4, or both relative to baseline.
14 . The method of claim 1 , wherein the subject has a level that is less than 1.75 times the upper limit of the normal range of A4.
15 . The method of claim 14 , wherein the subject has a level that is less than 1.5 times the upper limit of the normal range of A4.