High-strength testosterone undecanoate compositions

Abstract

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.