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 Cmax to serum testosterone Cave 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 Cave range for a male subject is provided.

What is claimed is: 
     
         1 . A method of replacement therapy in a male having a condition associated with a deficiency or absence of endogenous testosterone, said method comprising:
 orally administering to a male identified as in need of therapy, a pharmaceutical composition having about 20 wt % testosterone undecanoate (TU), about 16 wt % polyoxyl hydrogenated castor oil, and about 52 wt % oleic acid, twice a day with food, for a total daily dose of about 450-480 mg TU as a first dosing regimen; and   orally administering to said male, following determination of the male's steady state serum testosterone (T) level during the first dosing regimen, a pharmaceutical composition having about 20 wt % TU, about 16 wt % polyoxyl hydrogenated castor oil, and about 52 wt % oleic acid twice a day with food, for a total daily dose of TU that is within +/ 31  40% of the total daily dose administered in the first regimen, as a second dosing regimen based on the serum T level determined in the first dosing regimen.   
     
     
         2 . The method of  claim 1 , wherein the total daily dose of the second dosing regimen is greater than that of the total daily dose of the first dosing regimen. 
     
     
         3 . The method of  claim 2 , wherein the second dosing regimen provides a total daily dose of from 630-672 mg of TU. 
     
     
         4 . The method of  claim 1 , wherein the total daily dose of the second dosing regimen is less than that of the total daily dose of the first dosing regimen. 
     
     
         5 . The method of  claim 1 , wherein the total daily dose of the second dosing regimen is the same as that of the total daily dose of the first dosing regimen. 
     
     
         6 . The method of  claim 1 , wherein said administration twice a day with food is once in the morning with food and once in the evening with food. 
     
     
         7 . The method of  claim 1 , further comprising:
 orally administering to said male, following determination of the male's steady state serum testosterone (T) level during the second dosing regimen, a pharmaceutical composition having about 20 wt % TU, about 16 wt % polyoxyl hydrogenated castor oil, and about 52 wt % oleic acid twice a day with food, for a total daily dose of TU that is within +/−40% of the total daily dose administered in the second regimen, as a third dosing regimen based on the serum T level determined in the second dosing regimen.   
     
     
         8 . The method of  claim 7 , wherein the total daily dose of the third dosing regimen is greater than that of the total daily dose of the second dosing regimen. 
     
     
         9 . The method of  claim 7 , wherein the total daily dose of the third dosing regimen is less than that of the total daily dose of the first dosing regimen. 
     
     
         10 . The method of  claim 7 , wherein the total daily dose of the second dosing regimen is the same as that of the total daily dose of the first dosing regimen. 
     
     
         11 . The method of  claim 1 , that provides a serum testosterone C ave  in the in the eugonadal range. 
     
     
         12 . The method of  claim 1 , that provides a serum testosterone C ave  in the range of about 300 ng/dL to about 1100 mg/dL. 
     
     
         13 . The method of  claim 1 , wherein said male identified as in need of therapy has one morning serum T level below a normal range. 
     
     
         14 . The method of  claim 10 , wherein said one morning serum T level below the normal range is below 300 ng/dL testosterone. 
     
     
         15 . The method of  claim 1 , wherein said identifying a male in need of therapy comprises determining two morning serum T levels below a normal range. 
     
     
         16 . The method of  claim 15 , wherein said two morning serum T level below the normal range are below 300 ng/dL testosterone. 
     
     
         17 . The method of  claim 1 , wherein said determination of the male's steady state serum testosterone (T) level is at about 1-8 hours after administration of a dose of testosterone undecanoate. 
     
     
         18 . The method of  claim 6 , wherein said determination of the male's steady state serum testosterone (T) level is at about 1-8 hours after administration of the morning dose of testosterone undecanoate. 
     
     
         19 . The method of  claim 1 , wherein said determination of the male's steady state serum testosterone (T) level is at about 6 hours after administration of a dose of testosterone undecanoate. 
     
     
         20 . The method of  claim 6 , wherein said determination of the male's steady state serum testosterone (T) level is at about 6 hours after administration of the morning dose of testosterone undecanoate. 
     
     
         21 . The method of  claim 1 , wherein the total daily dose of TU of the second dosing regimen is within +40% of the total daily dose administered in the first regimen, when the male's steady state serum testosterone (T) level during the first dosing regimen is determined to be below a normal range. 
     
     
         22 . The method of  claim 1 , wherein the total daily dose of TU of the second dosing regimen is within −40% of the total daily dose administered in the first regimen, when the male's steady state serum testosterone (T) level during the first dosing regimen is determined to be above a normal range. 
     
     
         23 . The method of  claim 7 , wherein the total daily dose of TU of the third dosing regimen is within +40% of the total daily dose administered in the second regimen, when the male's steady state serum testosterone (T) level during the second dosing regimen is determined to be below a normal range. 
     
     
         24 . The method of  claim 1 , wherein the total daily dose of TU of the third dosing regimen is within −40% of the total daily dose administered in the second regimen, when the male's steady state serum testosterone (T) level during the second dosing regimen is determined to be above a normal range. 
     
     
         25 . The method of  claim 1 , wherein the total daily dose of TU of the second dosing regimen is within +40% of the total daily dose administered in the first regimen, when the male's steady state serum testosterone (T) level at about 6 hours after single dose administration during the first dosing regimen indicates a need for an increase in the total daily dose. 
     
     
         26 . The method of  claim 7 , wherein the total daily dose of TU of the third dosing regimen is within +40% of the total daily dose administered in the second regimen, when the male's steady state serum testosterone (T) level at about 6 hours after single dose administration during the second dosing regimen indicates a need for an increase in the total daily dose. 
     
     
         27 . The method of  claim 1 , wherein the total daily dose of TU of the second dosing regimen is within −40% of the total daily dose administered in the first regimen, when the male's steady state serum testosterone (T) level at about 6 hours after single dose administration during the first dosing regimen indicates a need for a decrease in the total daily dose. 
     
     
         28 . The method of  claim 7 , wherein the total daily dose of TU of the third dosing regimen is within +40% of the total daily dose administered in the second regimen, when the male's steady state serum testosterone (T) level at about 6 hours after single dose administration during the second dosing regimen indicates a need for a decrease in the total daily dose.