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 .- 105 . (canceled)
106 . A method of treating congenital adrenal hyperplasia (CAH) in a subject, comprising administering to the subject a therapeutically effective amount of (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 (SSR125543) or salt thereof, at a frequency of at least twice per day, and a steroid or a pharmaceutically acceptable salt thereof, wherein the steroid or pharmaceutically acceptable salt thereof is administered at a reduced dosage compared to a dosage of steroid or a pharmaceutically acceptable salt thereof administered alone, wherein the reduced dosage is in a 5 mg increment.
107 . The method of claim 106 , wherein the SSR125543 or salt thereof, and the steroid or pharmaceutically acceptable salt thereof are administered sequentially within 10 minutes to within about 24 hours.
108 . The method of claim 106 , wherein the CAH is non-classic CAH.
109 . The method of claim 106 , wherein the CAH is classic CAH.
110 . The method of claim 106 , wherein the steroid or a pharmaceutically acceptable salt thereof, is glucocorticoid, or a pharmaceutically acceptable salt thereof.
111 . The method of claim 110 , wherein the glucocorticoid or a pharmaceutically acceptable salt thereof, is prednisone, cortisone, prednisolone, triamcinolone, methylprednisolone, betamethasone, dexamethasone, hydrocortisone or a pharmaceutically acceptable salt thereof.
112 . The method of claim 106 , wherein the subject has a level of at least one steroid hormone that is less than two times an upper limit of a reference range of the at least one steroid hormone level.
113 . The method of claim 112 , wherein the steroid hormone is adrenocorticotropic hormone (ACTH), androstenedione (A4), 17-hydroxyprogesterone (17-OHP), deoxycorticosterone, 11-deoxycortisol, cortisol, corticosterone, aldosterone, pregnenolone, 17a-hydroxy pregnenolone, progesterone, dehydroepiandrosterone, androstenediol, testosterone, dihydrotestosterone, estrone, estradiol, and estriol.
114 . The method of claim 113 , wherein the subject has a level of 17-OHP that is less than two times an upper limit of a reference range of 17-OHP and a level of ACTH that is less than two times an upper limit of a reference range of ACTH.
115 . The method of claim 113 , wherein the subject has a level of 17-OHP that is less than two times an upper limit of a reference range of 17-OHP and a level of A4 that is less than two times an upper limit of a reference range of A4.
116 . The method of claim 113 , wherein the subject has a level of A4 that is less than two times an upper limit of a reference range of A4 and a level of ACTH that is less than two times an upper limit of a reference range of ACTH.
117 . The method of claim 112 , wherein levels of the steroid hormone in the subject is determined from a biological sample from the subject.
118 . The method of claim 117 , wherein the biological sample is selected from the group of blood, blood fractions, plasma, serum, and saliva.
119 . The method of claim 106 , wherein the SSR125543 or salt thereof, is administered in a dose of about 50 mg to about 200 mg total daily dose to the subject.
120 . The method of claim 106 , wherein the SSR125543 or salt thereof, is administered in a dose of about 200 mg total daily dose to the subject.
121 . The method of claim 106 , wherein the SSR125543 or salt thereof, is administered in a dose of about 100 mg total daily dose to the subject.
122 . The method of claim 106 , wherein the SSR125543 or salt thereof, is in the form of microparticles.
123 . The method of claim 106 , wherein the subject is tested to determine morning levels of A4 and ACTH.
124 . The method of claim 106 , wherein the subject is an adult patient.
125 . The method of claim 106 , wherein the subject is a pediatric patient.