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 .- 20 . (canceled)
21 . 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 said male a daily dosing regimen of a pharmaceutical composition comprising about 14 weight % (wt %) to about 35 wt % testosterone undecanoate and a carrier, that provides from about 430 mg to about 460 mg of testosterone undecanoate to said male per day;
(b) Determining the serum level of testosterone of said male during the daily dosing regimen at from 1-8 hours after single dose administration of said pharmaceutical composition at steady state; and
(c) Orally administering to said male to a maintenance daily dosing regimen of a pharmaceutical composition comprising about 14 wt % to about 35 wt % testosterone undecanoate and a carrier, that provides within 66% to 133% of the amount of testosterone undecanoate administered in step (a),
to provide a serum testosterone C ave in said male in the range of from about 300-1100 ng/dL.
22 . The method of claim 21 said carrier comprising a solubilizer and a dispersant.
23 . The method of claim 21 said carrier comprising a monoglyceride, diglyceride or both.
24 . The method of claim 21 said carrier comprising oleic acid.
25 . The method of claim 21 said carrier comprising a polyoxyethylene hydrogenated vegetable oil.
26 . The method of claim 21 said carrier comprising tocopherol.
27 . The method of claim 21 said daily dosing regimen or maintenance daily dosing regimen comprises twice daily dosing with said pharmaceutical composition.
28 . The method of claim 21 said orally administering comprises administration of the pharmaceutical composition with a meal.
29 . The method of claim 21 said carrier comprising a solubilizer in an amount of from about 50 wt % to about 86 wt % of the pharmaceutical composition.
30 . The method of claim 21 said pharmaceutical composition having at least 5% of said testosterone undecanoate not dissolved and at least 35% dissolved in said carrier.
31 . 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 said male a daily dosing regimen of a pharmaceutical composition comprising about 14 wt % to about 35 wt % testosterone undecanoate and a carrier to provide from about 430 mg testosterone undecanoate to about 460 mg testosterone undecanoate to said male per day;
(b) determining the serum level of testosterone of said male during the daily dosing regimen at a single time point from 1-8 hours after single dose administration of said pharmaceutical composition at steady state, Ct; and
(c) orally administering to said male a maintenance daily dosing regimen of a pharmaceutical composition comprising about 14 wt % to about 35 wt % testosterone undecanoate and a carrier, that provides within 66% to 133% of the amount of testosterone undecanoate administered in step (a),
said carrier comprising a monoglyceride, a diglyceride, a fatty acid, a polyoxyethylene hydrogenated vegetable oil or a combination thereof,
to provide a serum testosterone C ave in said male in the range of from about 300-1100 ng/dL.
32 . The method of claim 31 said carrier comprising a solubilizer and a dispersant.
33 . The method of claim 31 said carrier comprising a monoglyceride, diglyceride or both.
34 . The method of claim 31 said carrier comprising oleic acid.
35 . The method of claim 31 said carrier comprising a polyoxyethylene hydrogenated vegetable oil.
36 . The method of claim 31 said carrier comprising tocopherol.
37 . The method of claim 31 said daily dosing regimen or maintenance daily dosing regimen comprises twice daily dosing with said pharmaceutical composition.
38 . The method of claim 31 said orally administering comprises administration of the pharmaceutical composition with a meal.
39 . The method of claim 31 said pharmaceutical composition having at least 5% of said testosterone undecanoate not dissolved and at least 35% dissolved in said carrier.
40 . 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 said male subject a daily dosing regimen of a pharmaceutical composition comprising about 14 wt % to about 35 wt % testosterone undecanoate and a carrier to provide from about 430 mg testosterone undecanoate to about 460 mg testosterone undecanoate to said male per day;
(b) determining the serum level of testosterone of said male during the daily dosing regimen at a single time point from 1-8 hours after single dose administration of said pharmaceutical composition at steady state, Ct; and
(c) orally administering to said male a maintenance daily dosing regimen of a pharmaceutical composition comprising about 14% to about 35% testosterone undecanoate and a carrier, that provides within 66% to 133% of the amount of testosterone undecanoate administered in step (a), said carrier comprising a monoglyceride, a diglyceride, a polyoxyethylene hydrogenated vegetable oil or a combination thereof and said pharmaceutical composition having at least 5% of said testosterone undecanoate not dissolved and at least 35% dissolved in said carrier,
to provide a serum testosterone C ave in said male in the range of from about 300-1100 ng/dL.
41 . The method of claim 21 , said carrier comprising a triglyceride, a sterol derivative, an ionic hydrophilic surfactant, a non-ionic hydrophilic surfactant, an alcohol or a combination thereof.
42 . The method of claim 31 , said carrier further comprising a triglyceride, a sterol derivative, an ionic hydrophilic surfactant, a non-ionic hydrophilic surfactant, an alcohol or a combination thereof.
43 . The method of claim 40 , said carrier further comprising a fatty acid.
44 . The method of claim 21 , when used with a group of males provides a mean serum testosterone concentration in the range of about 350 ng/dL to 800 ng/dL.
45 . The method of claim 31 , when used with a group of males provides a mean serum testosterone concentration in the range of about 350 ng/dL to 800 ng/dL.
46 . The method of claim 40 , when used with a group of males provides a mean serum testosterone concentration in the range of about 350 ng/dL to 800 ng/dL.
47 . The method of claim 21 , said pharmaceutical composition disposed of in a capsule.
48 . The method of claim 31 , said pharmaceutical composition disposed of in a capsule.
49 . The method of claim 41 , said pharmaceutical composition disposed of in a capsule.