HIGH-STRENGTH TESTOSTERONE UNDECANOATE COMPOSITIONS
The present disclosure is drawn to pharmaceutical compositions and oral dosage capsules containing testosterone undecanoate, as well as related methods. The capsule includes a capsule shell and a capsule fill. The capsule fill can include a solubilizer and about 14 wt % to about 35 wt % testosterone undecanoate based on the total capsule fill. The oral dosage capsule is such that when a single oral administration to a male subject of one or more capsules with a total testosterone undecanoate daily dose of about 350 mg to about 650 mg it provides a ratio of serum testosterone C max to serum testosterone C ave of about 2.7 or less. In yet another embodiment, a method for providing a serum concentration of testosterone within a target serum testosterone concentration C ave range for a male subject is provided.
1 . A method for replacement therapy in a male having a condition associated with a deficiency or absence of endogenous testosterone said method comprising:
(a) orally administering to a male identified as having a morning serum testosterone level below normal, a daily dosing regimen of a pharmaceutical composition in one capsule in the morning and in one capsule in the evening, with food, said pharmaceutical composition comprising about 18 weight % (wt %) to about 20 wt % testosterone undecanoate and a carrier comprising oleic acid, polyoxyl 40 hydrogenated castor oil, and borage seed oil, that provides about 450 mg to 480 mg testosterone undecanoate to said male per day; and
(b) orally administering to the male, following a determination of the male's serum testosterone level at about 6 hours after single dose of the pharmaceutical composition at steady state during the daily dosing regimen, a daily dosing regimen of a pharmaceutical composition once in the morning and once in the evening, with food, comprising about 18 wt % to about 20 wt % testosterone undecanoate and a carrier comprising oleic acid, polyoxyl 40 hydrogenated castor oil, and borage seed oil, that provides within plus 33% or minus 34% of about 450 mg to 480 mg of testosterone undecanoate to said male per day to provide a serum testosterone Cave in said male in the range of from about 350-800 ng/dL and a Cmax of less than 2500 ng/dL.
2 . The method of claim, 1 wherein the Cmax is less than 1500 ng/dL.
3 . The method of claim 1 , wherein said pharmaceutical composition comprises about 52 wt % oleic acid.
4 . The method of claim 1 , wherein said pharmaceutical composition comprises about 20 wt % testosterone undecanoate.
5 . The method of claim 4 , wherein said pharmaceutical composition comprises about 16 wt % polyoxyl 40 hydrogenated castor oil.
6 . The method of claim 1 , wherein said daily dosing regimen of (a) provides about 480 mg per day of testosterone undecanoate.
7 . The method of claim 1 , wherein said daily dosing regimen of (b) provides within plus 33% of about 450 mg to 480 mg testosterone undecanoate and said pharmaceutical composition is provided in two capsules in the morning and in two capsules in the evening.
8 . The method of claim 1 , wherein said daily dosing regimen of (b) provides within minus 34% of about 450 mg to 480 mg testosterone undecanoate per day.
9 . The method of claim 1 , wherein said daily dosing regimen of (b) provides plus 33% of about 450 mg to 480 mg testosterone undecanoate per day and said pharmaceutical composition is provided in two capsules in the morning and in two capsules in the evening.
10 . The method of claim 4 , wherein said daily dosing regimen of (b) provides within plus 33% of about 450 mg to 480 mg testosterone undecanoate and said pharmaceutical composition is provided in two capsules in the morning and in two capsules in the evening.
11 . The method of claim 4 , wherein said daily dosing regimen of (b) provides within minus 34% of about 450 mg to 480 mg testosterone undecanoate per day.
12 . The method of claim 4 , wherein said daily dosing regimen of (b) provides plus 33% of about 450 mg to 480 mg testosterone undecanoate per day and said pharmaceutical composition is provided in two capsules in the morning and in two capsules in the evening.
13 . The method of claim 5 , wherein said daily dosing regimen of (a) provides about 480 mg per day of testosterone undecanoate.
14 . The method of claim 5 , wherein said daily dosing regimen of (b) provides within plus 33% of about 450 mg to 480 mg testosterone undecanoate and said pharmaceutical composition is provided in two capsules in the morning and in two capsules in the evening.
15 . The method of claim 5 , wherein said daily dosing regimen of (b) provides within minus 34% of about 450 mg to 480 mg testosterone undecanoate per day.
16 . The method of claim 5 , wherein said daily dosing regimen of (b) provides plus 33% of about 450 mg to 480 mg testosterone undecanoate per day and said pharmaceutical composition is provided in two capsules in the morning and in two capsules in the evening.
17 . The method of claim 6 , wherein said pharmaceutical composition provides upon single dose administration a ratio of serum testosterone Cmax to Cave of about 2.7 or less.
18 . The method of claim 6 , wherein said pharmaceutical composition provides upon single dose administration a dose-normalized serum testosterone Cave of about 1.9×10-6 dL-1 or higher
19 . The method of claim 7 , wherein said pharmaceutical composition provides upon single dose administration a ratio of serum testosterone Cmax to Cave of about 2.7 or less.
20 . The method of claim 7 , wherein said pharmaceutical composition provides upon single dose administration a dose-normalized serum testosterone Cave of about 1.9×10-6 dL-1 or higher.
21 . The method of claim 8 , wherein said pharmaceutical composition provides upon single dose administration a ratio of serum testosterone Cmax to Cave of about 2.7 or less.
22 . The method of claim 8 , wherein said pharmaceutical composition provides upon single dose administration a dose-normalized serum testosterone Cave of about 1.9×10-6 dL-1 or higher.
23 . The method of claim 9 , wherein said pharmaceutical composition provides upon single dose administration a ratio of serum testosterone Cmax to Cave of about 2.7 or less.
24 . The method of claim 9 , wherein said pharmaceutical composition provides upon single dose administration a dose-normalized serum testosterone Cave of about 1.9×10-6 dL-1 or higher.
25 . The method of claim 10 , wherein said pharmaceutical composition provides upon single dose administration a ratio of serum testosterone Cmax to Cave of about 2.7 or less.
26 . The method of claim 10 , wherein said pharmaceutical composition provides upon single dose administration a dose-normalized serum testosterone Cave of about 1.9×10-6 dL-1 or higher.
27 . The method of claim 11 , wherein said pharmaceutical composition provides upon single dose administration a dose-normalized serum testosterone Cave of about 1.9×10-6 dL-1 or higher.
28 . The method of claim 10 , wherein said pharmaceutical composition provides upon single dose administration a ratio of serum testosterone Cmax to Cave of about 2.7 or less.