US2021361664A1PendingUtilityA1

Corticotropin releasing factor receptor antagonists

66
Assignee: SPRUCE BIOSCIENCES INCPriority: Aug 14, 2017Filed: Aug 14, 2018Published: Nov 25, 2021
Est. expiryAug 14, 2037(~11.1 yrs left)· nominal 20-yr term from priority
A61P 5/08A61K 9/2077A61P 3/00A61P 15/00A61P 5/00A61P 5/38A61P 5/24A61P 15/08A61K 31/5377A61K 9/14A61K 2300/00C07D 487/04A61K 9/48A61K 31/573A61K 9/4825
66
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Claims

Abstract

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).

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A method of treating congenital adrenal hyperplasia (CAH) in a subject in need thereof, comprising administering a pharmaceutical composition comprising Compound 1: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt or solvate thereof, wherein Compound 1 is administered at a dose between about 50 mg/day and about 1600 mg/day. 
     
     
         2 . The method of  claim 1 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, is administered at a dose between about 50 mg/day and about 1200 mg/day. 
     
     
         3 . The method of  claim 1  or  2 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, is administered at a dose between about 50 mg/day and about 1000 mg/day. 
     
     
         4 . The method of any one of  claims 1  to  3 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, is administered at a dose between about 50 mg/day and about 800 mg/day. 
     
     
         5 . The method of any one of  claims 1  to  4 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, is administered at a dose between about 100 mg/day and about 600 mg/day. 
     
     
         6 . The method of any one of  claims 1  to  5 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, is administered at a dose between about 200 mg/day and 400 mg/day. 
     
     
         7 . The method of any one of  claims 1  to  6 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, is administered at a dose of about 200 mg/day. 
     
     
         8 . The method of any one of  claims 1  to  7 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, is in the form of microparticles. 
     
     
         9 . The method of  claim 8 , wherein the average size of the microparticles is between about 1 μm and about 20 μm. 
     
     
         10 . The method of  claim 8  or  9 , wherein the average size of the microparticles is between about 5 μm and about 15 μm. 
     
     
         11 . The method of any one of  claims 8  to  10 , wherein the average size of the microparticles is less than about 10 μm. 
     
     
         12 . The method of any one of  claims 1  to  11 , wherein the pharmaceutical composition is in the form of a capsule or a tablet. 
     
     
         13 . The method of any one of  claims 1  to  12 , wherein the pharmaceutical composition is in the form of a capsule. 
     
     
         14 . The method of  claim 13 , wherein the capsule is a hard gelatin capsule. 
     
     
         15 . The method of  claim 13 , wherein the capsule is a soft gelatin capsule. 
     
     
         16 . The method of any one of  claims 13  to  15 , wherein the capsule is formed using materials selected from the group consisting of natural gelatin, synthetic gelatin, pectin, casein, collagen, protein, modified starch, polyvinylpyrrolidone, acrylic polymers, cellulose derivatives, and any combinations thereof. 
     
     
         17 . The method of any one of  claims 13  to  16 , wherein the pharmaceutical composition is free of additional excipients. 
     
     
         18 . The method of any one of  claims 13  to  16 , wherein the pharmaceutical composition further comprises one or more pharmaceutically acceptable excipients. 
     
     
         19 . The method of any one of  claims 1  to  12 , wherein the pharmaceutical composition is in the form of a tablet. 
     
     
         20 . The method of  claim 19 , wherein the pharmaceutical composition further comprises one or more pharmaceutically acceptable excipients. 
     
     
         21 . The method of any one of  claims 1  to  20 , wherein the pharmaceutical composition comprises between about 1 mg and about 500 mg of Compound 1, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         22 . The method of any one of  claims 1  to  21 , wherein the pharmaceutical composition comprises between about 5 mg and about 500 mg of Compound 1, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         23 . The method of any one of  claims 1  to  22 , wherein the pharmaceutical composition comprises between about 10 mg and about 500 mg of Compound 1, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         24 . The method of any one of  claims 1  to  23 , wherein the pharmaceutical composition comprises between about 10 mg and about 300 mg of Compound 1, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         25 . The method of any one of  claims 1  to  24 , wherein the pharmaceutical composition comprises between about 10 mg and about 100 mg of Compound 1, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         26 . The method of any one of  claims 1  to  23 , wherein the pharmaceutical composition comprises between about 50 mg and about 500 mg of Compound 1, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         27 . The method of any one of  claims 1  to  23 , wherein the pharmaceutical composition comprises between about 100 mg and about 400 mg of Compound 1, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         28 . The method of any one of  claims 1  to  24 , wherein the pharmaceutical composition comprises between about 100 mg and about 300 mg of Compound 1, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         29 . The method of any one of  claims 1  to  24 , wherein the pharmaceutical composition comprises between about 150 mg and about 250 mg of Compound 1, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         30 . The method of any one of  claims 1  to  23 , wherein the pharmaceutical composition comprises about 400 mg of Compound 1, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         31 . The method of any one of  claims 1  to  24 , wherein the pharmaceutical composition comprises about 300 mg of Compound 1, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         32 . The method of any one of  claims 1  to  24 , wherein the pharmaceutical composition comprises about 250 mg of Compound 1, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         33 . The method of any one of  claims 1  to  24 , wherein the pharmaceutical composition comprises about 200 mg of Compound 1, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         34 . The method of any one of  claims 1  to  24 , wherein the pharmaceutical composition comprises about 150 mg of Compound 1, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         35 . The method of any one of  claims 1  to  25 , wherein the pharmaceutical composition comprises about 100 mg of Compound 1, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         36 . The method of any one of  claims 1  to  25 , wherein the pharmaceutical composition comprises about 80 mg of Compound 1, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         37 . The method of any one of  claims 1  to  25 , wherein the pharmaceutical composition comprises about 60 mg of Compound 1, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         38 . The method of any one of  claims 1  to  25 , wherein the pharmaceutical composition comprises about 50 mg of Compound 1, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         39 . The method of any one of  claims 1  to  25 , wherein the pharmaceutical composition comprises about 30 mg of Compound 1, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         40 . The method of any one of  claims 1  to  39 , wherein the pharmaceutical composition provides a Compound 1 T max  of about 2 to about 6 hours in a subject. 
     
     
         41 . The method of any one of  claims 1  to  40 , wherein the pharmaceutical composition provides a Compound 1 T max  of about 3 to about 5 hours in a subject. 
     
     
         42 . The method of any one of  claims 1  to  40 , wherein the pharmaceutical composition provides a Compound 1 T max  of about 6 hours in a subject. 
     
     
         43 . The method of any one of  claims 1  to  41 , wherein the pharmaceutical composition provides a Compound 1 T max  of about 5 hours in a subject. 
     
     
         44 . The method of any one of  claims 1  to  41 , wherein the pharmaceutical composition provides a Compound 1 T max  of about 4 hours in a subject. 
     
     
         45 . The method of any one of  claims 1  to  41 , wherein the pharmaceutical composition provides a Compound 1 T max  of about 3 hours in a subject. 
     
     
         46 . The method of any one of  claims 1  to  45 , wherein the pharmaceutical composition is administered in the fed state. 
     
     
         47 . The method of any one of  claims 1  to  45 , wherein the pharmaceutical composition is administered in the fasted state. 
     
     
         48 . The method of any one of  claims 1  to  47 , wherein the pharmaceutical composition is administered once a day. 
     
     
         49 . The method of any one of  claims 1  to  47 , wherein the pharmaceutical composition is administered twice a day. 
     
     
         50 . The method of any one of  claims 1  to  47 , wherein the pharmaceutical composition is administered three times a day. 
     
     
         51 . The method of any of  claims 1  to  50 , further comprising administering a glucocorticoid. 
     
     
         52 . The method of  claim 51 , wherein the amount of glucocorticoid administered is reduced as compared to a method not comprising administering Compound 1, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         53 . The method of  claim 52 , wherein the amount of glucocorticoid used is reduced from a supraphysiologic amount to a physiologic amount. 
     
     
         54 . The method of  claim 52 , wherein the amount of glucocorticoid is reduced by about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, or about 60%. 
     
     
         55 . The method of any one of  claims 52  to  54 , wherein the symptoms associated with high-dose glucocorticoid therapy are reduced. 
     
     
         56 . The method of  claim 55 , wherein the symptoms associated with high-dose glucocorticoid therapy are obesity, insulin resistance, metabolic abnormalities, hypertension, cardiovascular diseases, or osteoporosis. 
     
     
         57 . The method of any one of  claims 51  to  56 , wherein the glucocorticoid is beclomethasone, betamethasone, budesonide, cortisone, dexamethasone, hydrocortisone, methylprednisolone, prednisolone, prednisone, or triamcinolone. 
     
     
         58 . The method of any one of  claims 51  to  57 , wherein the glucocorticoid is hydrocortisone. 
     
     
         59 . The method of  claim 58 , wherein the hydrocortisone is administered at a dose less than about 15 mg/day. 
     
     
         60 . The method of  claim 58  or  59 , wherein the hydrocortisone is administered at a dose less than about 10 mg/day. 
     
     
         61 . The method of any one of  claims 58  to  60 , wherein the hydrocortisone is administered at a dose less than about 5 mg/day. 
     
     
         62 . The method of any one of  claims 51  to  61 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, and the glucocorticoid are administered concurrently. 
     
     
         63 . The method of any one of  claims 51  to  62 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, and the glucocorticoid are administered sequentially. 
     
     
         64 . The method of any one of  claims 51  to  62 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, and the glucocorticoid are administered sequentially within 24 hours. 
     
     
         65 . The method of any one of  claims 51  to  62 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, and the glucocorticoid are administered sequentially within 8 hours. 
     
     
         66 . The method of any one of  claims 51  to  62 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, and the glucocorticoid are administered sequentially within 2 hours. 
     
     
         67 . The method of any one of  claims 51  to  62 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, and the glucocorticoid are administered sequentially within 30 minutes. 
     
     
         68 . The method of any one of  claims 1  to  67 , further comprising administering a mineralocorticoid. 
     
     
         69 . The method of  claim 68 , wherein the mineralocorticoid is fludrocortisone. 
     
     
         70 . The method of any one of  claims 1  to  69 , wherein the pharmaceutical composition is administered at bedtime. 
     
     
         71 . The method of any one of  claims 1  to  70 , wherein the pharmaceutical composition is administered less than about 4 hours before sleep. 
     
     
         72 . The method of any one of  claims 1  to  70 , wherein the pharmaceutical composition is administered less than about 2 hours before sleep. 
     
     
         73 . The method of any one of  claims 1  to  70 , wherein the pharmaceutical composition is administered less than about 30 mins before sleep. 
     
     
         74 . The method of any one of  claims 1  to  70 , wherein the pharmaceutical composition is administered in the evening. 
     
     
         75 . The method of any one of  claims 1  to  70 , wherein the pharmaceutical composition is administered at about 10 pm at night. 
     
     
         76 . The method of any one of  claims 1  to  70 , wherein the pharmaceutical composition is administered at or before the expected circadian release of adrenocorticotropic hormone (ACTH). 
     
     
         77 . The method of any one of  claims 1  to  70 , wherein the pharmaceutical composition is administered about 3-4 hours before the expected circadian release of adrenocorticotropic hormone (ACTH). 
     
     
         78 . The method of any one of  claims 1  to  77 , wherein CAH is classic CAH. 
     
     
         79 . The method of any one of  claims 1  to  77 , wherein CAH is non-classic CAH. 
     
     
         80 . A method of treating congenital adrenal hyperplasia (CAH) in a subject in need thereof, the method comprising:
 (iv) measuring a hormone level in the subject in need thereof;   (v) administering Compound 1:   
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt or solvate thereof;
 (vi) repeating steps (i) and (ii) until the hormone level reaches a pre-determined range followed by a maintenance therapy of a daily dosing of compound 1. 
 
     
     
         81 . The method of  claim 80 , wherein the hormone is 17α-Hydroxyprogesterone (17-OHP), adrenocorticotropic hormone (ACTH), testosterone, or androstenedione. 
     
     
         82 . The method of  claim 81 , wherein the hormone is 17-OHP, and the pre-determined range is from about 200 ng/dL to about 400 ng/dL. 
     
     
         83 . The method of  claim 81 , wherein the hormone is ACTH, and the pre-determined range is below about 100 pg/mL. 
     
     
         84 . The method of  claim 81 , wherein the hormone is testosterone and the pre-determined range is from about 14 ng/dL to about 76 ng/dL. 
     
     
         85 . The method of  claim 81 , wherein the hormone is androstenedione and the pre-determined range is from about 30 ng/dL to about 150 ng/dL in males. 
     
     
         86 . The method of  claim 81 , wherein the hormone is androstenedione and the pre-determined range is from about 40 ng/dL to about 200 ng/dL in females. 
     
     
         87 . The method of any one of  claims 80  to  86 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, is administered at a dose between about 200 mg/day and about 1600 mg/day. 
     
     
         88 . The method of any one of  claims 80  to  87 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, is administered at a dose between about 200 mg/day and about 1200 mg/day. 
     
     
         89 . The method of any one of  claims 80  to  88 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, is administered at a dose between about 200 mg/day and about 1000 mg/day. 
     
     
         90 . The method of any one of  claims 80  to  89 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, is administered at a dose between about 200 mg/day and about 800 mg/day. 
     
     
         91 . The method of any one of  claims 80  to  90 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, is administered at a dose between about 200 mg/day and about 600 mg/day. 
     
     
         92 . The method of any one of  claims 80  to  91 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, is administered at a dose between about 200 mg/day and 400 mg/day. 
     
     
         93 . The method of any one of  claims 80  to  92 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, is administered at a dose of about 200 mg/day. 
     
     
         94 . The method of any one of  claims 80  to  86 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, is administered at a dose between about 50 mg/day and about 1600 mg/day. 
     
     
         95 . The method of  claim 94 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, is administered at a dose between about 50 mg/day and about 1200 mg/day. 
     
     
         96 . The method of  claim 94  or  95 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, is administered at a dose between about 50 mg/day and about 1000 mg/day. 
     
     
         97 . The method of any one of  claims 94  to  96 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, is administered at a dose between about 50 mg/day and about 800 mg/day. 
     
     
         98 . The method of any one of  claims 94  to  97 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, is administered at a dose between about 50 mg/day and about 600 mg/day. 
     
     
         99 . The method of any one of  claims 94  to  98 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, is administered at a dose between about 50 mg/day and 400 mg/day. 
     
     
         100 . The method of any one of  claims 94  to  99 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, is administered at a dose between 50 mg/day and 200 mg/day. 
     
     
         101 . The method of any one of  claims 94  to  99 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, is administered at a dose of about 50 mg/day. 
     
     
         102 . The method of any one of  claims 80  to  101 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, is in the form of microparticles. 
     
     
         103 . The method of  claim 102 , wherein the average size of the microparticles is between about 1 μm and about 20 μm. 
     
     
         104 . The method of  claim 102  or  103 , wherein the average size of the microparticles is between about 5 μm and about 15 μm. 
     
     
         105 . The method of any one of  claims 102  to  104 , wherein the average size of the microparticles is less than about 10 μm. 
     
     
         106 . The method of any one of  claims 80  to  105 , wherein Compound 1 is formulated in a pharmaceutical composition in the form of a capsule or a tablet. 
     
     
         107 . The method of  claim 106 , wherein the pharmaceutical composition is in the form of a capsule. 
     
     
         108 . The method of  claim 107 , wherein the capsule is a hard gelatin capsule. 
     
     
         109 . The method of  claim 107 , wherein the capsule is a soft gelatin capsule. 
     
     
         110 . The method of any one of  claims 106  to  109 , wherein the capsule is formed using materials selected from the group consisting of natural gelatin, synthetic gelatin, pectin, casein, collagen, protein, modified starch, polyvinylpyrrolidone, acrylic polymers, cellulose derivatives, and any combinations thereof. 
     
     
         111 . The method of any one of  claims 106  to  110 , wherein the pharmaceutical composition is free of additional excipients. 
     
     
         112 . The method of any one of  claims 106  to  110 , wherein the pharmaceutical composition further comprises one or more pharmaceutically acceptable excipients. 
     
     
         113 . The method of  claim 106 , wherein the pharmaceutical composition is in the form of a tablet. 
     
     
         114 . The method of  claim 113 , wherein the pharmaceutical composition further comprises one or more pharmaceutically acceptable excipients. 
     
     
         115 . The method of any one of  claims 106  to  114 , wherein the pharmaceutical composition comprises between about 1 mg and about 500 mg of Compound 1, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         116 . The method of any one of  claims 106  to  115 , wherein the pharmaceutical composition comprises between about 5 mg and about 500 mg of Compound 1, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         117 . The method of any one of  claims 106  to  116 , wherein the pharmaceutical composition comprises between about 10 mg and about 500 mg of Compound 1, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         118 . The method of any one of  claims 106  to  117 , wherein the pharmaceutical composition comprises between about 10 mg and about 300 mg of Compound 1, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         119 . The method of any one of  claims 106  to  118 , wherein the pharmaceutical composition comprises between about 10 mg and about 100 mg of Compound 1, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         120 . The method of any one of  claims 106  to  117 , wherein the pharmaceutical composition comprises between about 50 mg and about 500 mg of Compound 1, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         121 . The method of any one of  claims 106  to  117 , wherein the pharmaceutical composition comprises between about 100 mg and about 400 mg of Compound 1, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         122 . The method of any one of  claims 106  to  118 , wherein the pharmaceutical composition comprises between about 100 mg and about 300 mg of Compound 1, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         123 . The method of any one of  claims 106  to  118 , wherein the pharmaceutical composition comprises between about 150 mg and about 250 mg of Compound 1, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         124 . The method of any one of  claims 106  to  117 , wherein the pharmaceutical composition comprises about 400 mg of Compound 1, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         125 . The method of any one of  claims 106  to  118 , wherein the pharmaceutical composition comprises about 300 mg of Compound 1, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         126 . The method of any one of  claims 106  to  118 , wherein the pharmaceutical composition comprises about 250 mg of Compound 1, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         127 . The method of any one of  claims 106  to  118 , wherein the pharmaceutical composition comprises about 200 mg of Compound 1, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         128 . The method of any one of  claims 106  to  118 , wherein the pharmaceutical composition comprises about 150 mg of Compound 1, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         129 . The method of any one of  claims 106  to  118 , wherein the pharmaceutical composition comprises about 100 mg of Compound 1, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         130 . The method of any one of  claims 106  to  118 , wherein the pharmaceutical composition comprises about 80 mg of Compound 1, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         131 . The method of any one of  claims 106  to  118 , wherein the pharmaceutical composition comprises about 60 mg of Compound 1, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         132 . The method of any one of  claims 106  to  118 , wherein the pharmaceutical composition comprises about 50 mg of Compound 1, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         133 . The method of any one of  claims 106  to  118 , wherein the pharmaceutical composition comprises about 30 mg of Compound 1, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         134 . The method of any one of  claims 106  to  133 , wherein the pharmaceutical composition provides a Compound 1 T max  of about 2 to about 6 hours in a subject. 
     
     
         135 . The method of any one of  claims 106  to  118 , wherein the pharmaceutical composition provides a Compound 1 T max  of about 3 to about 5 hours in a subject. 
     
     
         136 . The method of any one of  claims 106  to  118 , wherein the pharmaceutical composition provides a Compound 1 T max  of about 6 hours in a subject. 
     
     
         137 . The method of any one of  claims 106  to  135 , wherein the pharmaceutical composition provides a Compound 1 T max  of about 5 hours in a subject. 
     
     
         138 . The method of any one of  claims 106  to  135 , wherein the pharmaceutical composition provides a Compound 1 T max  of about 4 hours in a subject. 
     
     
         139 . The method of any one of  claims 106  to  135 , wherein the pharmaceutical composition provides a Compound 1 T max  of about 3 hours in a subject. 
     
     
         140 . The method of any one of  claims 106  to  139 , wherein the pharmaceutical composition is administered in the fed state. 
     
     
         141 . The method of any one of  claims 106  to  140 , wherein the pharmaceutical composition is administered in the fasted state. 
     
     
         142 . The method of any one of  claims 106  to  141 , wherein the pharmaceutical composition is administered once a day. 
     
     
         143 . The method of any one of  claims 106  to  141 , wherein the pharmaceutical composition is administered twice a day. 
     
     
         144 . The method of any one of  claims 106  to  141 , wherein the pharmaceutical composition is administered three times a day. 
     
     
         145 . The method of any of  claims 80  to  144 , further comprising administering a glucocorticoid. 
     
     
         146 . The method of  claim 145 , wherein the amount of glucocorticoid administered is reduced as compared to a method not comprising administering Compound 1, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         147 . The method of  claim 145 , wherein the amount of glucocorticoid used is reduced from a supraphysiologic amount to a physiologic amount. 
     
     
         148 . The method of  claim 145 , wherein the amount of glucocorticoid is reduced by about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, or about 60%. 
     
     
         149 . The method of any one of  claims 145  to  148 , wherein the symptoms associated with high-dose glucocorticoid therapy are reduced. 
     
     
         150 . The method of  claim 149 , wherein the symptoms associated with high-dose glucocorticoid therapy are obesity, insulin resistance, metabolic abnormalities, hypertension, cardiovascular diseases, or osteoporosis. 
     
     
         151 . The method of any one of  claims 145  to  150 , wherein the glucocorticoid is beclomethasone, betamethasone, budesonide, cortisone, dexamethasone, hydrocortisone, methylprednisolone, prednisolone, prednisone, or triamcinolone. 
     
     
         152 . The method of any one of  claims 145  to  151 , wherein the glucocorticoid is hydrocortisone. 
     
     
         153 . The method of  claim 152 , wherein the hydrocortisone is administered at a dose less than about 15 mg/day. 
     
     
         154 . The method of  claim 152  or  153 , wherein the hydrocortisone is administered at a dose less than about 10 mg/day. 
     
     
         155 . The method of any one of  claims 152  to  154 , wherein the hydrocortisone is administered at a dose less than about 5 mg/day. 
     
     
         156 . The method of any one of  claims 152  to  155 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, and the glucocorticoid are administered concurrently. 
     
     
         157 . The method of any one of  claims 152  to  155 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, and the glucocorticoid are administered sequentially. 
     
     
         158 . The method of any one of  claims 152  to  155 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, and the glucocorticoid are administered sequentially within 24 hours. 
     
     
         159 . The method of any one of  claims 152  to  155 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, and the glucocorticoid are administered sequentially within 8 hours. 
     
     
         160 . The method of any one of  claims 152  to  155 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, and the glucocorticoid are administered sequentially within 2 hours. 
     
     
         161 . The method of any one of  claims 152  to  155 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, and the glucocorticoid are administered sequentially within 30 minutes. 
     
     
         162 . The method of any one of  claims 80  to  161 , further comprising administering a mineralocorticoid. 
     
     
         163 . The method of  claim 162 , wherein the mineralocorticoid is fludrocortisone. 
     
     
         164 . The method of any one of  claims 80  to  163 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, is administered at bedtime. 
     
     
         165 . The method of any one of  claims 80  to  163 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, is administered less than about 4 hours before sleeping. 
     
     
         166 . The method of any one of  claims 80  to  163 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, is administered less than about 2 hours before sleeping. 
     
     
         167 . The method of any one of  claims 80  to  163 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, is administered less than about 30 mins before sleeping. 
     
     
         168 . The method of any one of  claims 80  to  163 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, is administered in the evening. 
     
     
         169 . The method of any one of  claims 80  to  163 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, is administered at 10 pm at night. 
     
     
         170 . The method of any one of  claims 80  to  163 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, is administered at or before the expected circadian release of adrenocorticotropic hormone (ACTH). 
     
     
         171 . The method of any one of  claims 80  to  163 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, is administered about 3-4 hours before the expected circadian release of adrenocorticotropic hormone (ACTH). 
     
     
         172 . The method of any one of  claims 80  to  171 , wherein CAH is classic CAH. 
     
     
         173 . The method of any one of  claims 80  to  171 , wherein CAH is non-classic CAH. 
     
     
         174 . A method of any one of  claims 1  to  173 , wherein the subject in need thereof is from about 12 years of age to about 20 years of age. 
     
     
         175 . A method of improving hyperandrogenic symptoms in a subject in need thereof, comprising administering a pharmaceutical composition comprising Compound 1: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt or solvate thereof, wherein Compound 1 is administered at a dose between about 50 mg/day and about 1600 mg/day. 
     
     
         176 . A method of  claim 175 , wherein the hyperandrogenic symptoms are selected from the group consisting of acne, hirsutism and alopecia. 
     
     
         177 . A method of treating menstrual irregularity, ovulatory dysfunction or infertility, in a subject in need thereof, comprising administering a pharmaceutical composition comprising Compound 1: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt or solvate thereof, wherein Compound 1 is administered at a dose between about 50 mg/day and about 1600 mg/day. 
     
     
         178 . A method of improving metabolic symptoms in a subject in need thereof, comprising administering a pharmaceutical composition comprising Compound 1: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt or solvate thereof, wherein Compound 1 is administered at a dose between about 50 mg/day and about 1600 mg/day. 
     
     
         179 . A method of  claim 178 , wherein the metabolic symptoms are selected from the group consisting of body weight, BMI, waist circumference, blood pressure and glycemic control. 
     
     
         180 . A method of improving quality of life in a subject in need thereof, comprising administering a pharmaceutical composition comprising Compound 1: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt or solvate thereof, wherein Compound 1 is administered at a dose between about 50 mg/day and about 1600 mg/day, wherein treatment results in an improved quality of life.

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