ENHANCED BIOAVAILABILITY OF N-(2,6-BIS(1-METHYLETHYL)PHENYL)-N'-((1-(4-(DIMETHYLAMINO)-PHENYL)CYCLOPENTYL)METHYL)UREA HYDROCHLORIDE
Methods for enhancing the bioavailability of N-(2,6-bis(1-methylethyl)phenyl)-N′-((1-(4-(dimethylamino)phenyl)cyclopentyl)-methyl)urea hydrochloride (ATR-101) through administration with food, and compositions and kits related thereto.
1 . A method of increasing the bioavailability of ATR-101 comprising orally administering to a subject in need thereof ATR-101 in unit dosage form at or near the time of oral administration of food.
2 . The method of claim 1 , wherein the ATR-101 in unit dosage form is administered at the same time or within about 30 minutes after the oral administration of food.
3 . The method of claim 1 , wherein the food is a high fat, high calorie meal.
4 . The method of claim 1 , wherein the mean maximum plasma concentration (C max ) of ATR-101 in the subject in need thereof is increased when the unit dosage form of ATR-101 is administered with a meal, compared to when the unit dosage form of ATR-101 is administered under fasting conditions.
5 . The method of claim 4 , wherein C max increases by at least about 50%.
6 . The method of claim 4 , wherein C max increases by at least about 100%.
7 . The method of claim 1 , wherein the area under the plasma concentration time curve (AUC 0-t ) of ATR- in the subject in need thereof is increased when the unit dosage form of ATR-101 is administered with a meal, compared to when ATR-101 is administered under fasting conditions.
8 . The method of claim 7 , wherein AUC 0-t increases by at least about 50%.
9 . The method of claim 7 , wherein AUC 0-t increases by at least about 100%.
10 . The method of claim 1 , wherein the subject has a non-cancerous disorder.
11 . The method of claim 10 , wherein the subject has a non-cancerous endocrine disorder.
12 . The method of claim 10 , wherein the subject has Cushing's syndrome.
13 . The method of claim 10 , wherein the subject has congenital adrenal hyperplasia.
14 . The method of claim 1 , wherein the subject has a cancerous disorder.
15 . The method of claim 14 , wherein the subject has ACC.
16 . The method of claim 14 , wherein the subject has prostate cancer.
17 . A solid pharmaceutical composition in a unit dosage form suitable for oral administration, comprising N-(2,6-bis(1-methylethyl)phenyl)-N′-((1-(4-(dimethylamino)phenyl)-cyclopentyl)methyl)urea hydrochloride (ATR-101) in combination with one or more pharmaceutically acceptable carriers or excipients, wherein ATR-101 is present in the unit dosage form at a level ranging from about 250-750 mg as measured as the free base form of ATR-101.
18 .- 33 . (canceled)
34 . A method of administering a solid pharmaceutical composition of claim 17 , comprising orally administering to a subject in need thereof ATR-101 in unit dosage form.
35 .- 50 . (canceled)
51 . A kit comprising a plurality of oral unit dosage forms of the solid pharmaceutical composition of claim 17 in combination with instructions for co-administration with food at or near the time of oral administration of ATR-101 in unit dosage form.