Oral testosterone tridecanoate therapy

Abstract

The present disclosure provides methods and compositions for testosterone replacement therapy. The methods and compositions employ a fixed dose dosing regimen that does not require titration or dose adjustments and that can provide a therapeutically effective amount of a testosterone ester while avoiding unacceptably high testosterone levels.

What is claimed is: 
     
         1 . A method of restoring serum testosterone levels to a normal eugonadal range in a male having a condition associated with a deficiency or absence of endogenous testosterone, comprising orally administering a pharmaceutical composition comprising a therapeutically effective amount of testosterone tridecanoate (T13) in a fixed dose administration regimen with food. 
     
     
         2 . The method of  claim 1 , wherein the composition further comprises an additive. 
     
     
         3 . The method of  claim 1 , wherein the fixed dose administration regimen provides a total daily dose of T13 of from 750-1150 mg. 
     
     
         4 . The method of  claim 1 , wherein the fixed dose administration regimen comprises administering said composition once or twice daily. 
     
     
         5 . The method of  claim 1 , wherein said composition is in the form of a hard or soft capsule. 
     
     
         6 . The method of  claim 1 , wherein a unit dosage form of the composition comprises about 100-500 mg T13. 
     
     
         7 . The method of  claim 1 , further comprising measuring a therapy discontinuation criterion that indicates an advised discontinuation of therapy where serum testosterone (T) levels are consistently >2500 ng/dl. 
     
     
         8 . A method of restoring daily average serum testosterone (C avg ) to a normal eugonadal range in at least 75% of males in a population having a condition associated with a deficiency or absence of endogenous testosterone, comprising oral administration of an oral dosage form comprising a therapeutically effective amount of testosterone tridecanoate (T13) in a fixed dose administration regimen with food. 
     
     
         9 . The method of  claim 8 , wherein the oral dosage form further comprises an additive. 
     
     
         10 . The method of  claim 8 , wherein the fixed dose administration regimen provides a total daily T13 dose of from 750-1150 mg. 
     
     
         11 . The method of  claim 8 , wherein the fixed dose administration regimen comprises administering said oral dosage form once or twice daily. 
     
     
         12 . The method of  claim 8 , wherein said dosage form is in the form of a hard or soft capsule. 
     
     
         13 . The method of  claim 8 , wherein the therapeutically effective amount is about 100-500 mg. 
     
     
         14 . The method of  claim 8 , further comprising measuring a therapy discontinuation criterion that indicates an advised discontinuation of therapy where serum T levels are consistently >2500 ng/dl. 
     
     
         15 . A method of treating a condition associated with a deficiency or absence of endogenous testosterone in a male patient, comprising: orally administering a fixed dose of 375-575 mg of testosterone tridecanoate (T13) twice daily or 750-1150 mg once daily in a fixed dose dosing regimen with food. 
     
     
         16 . The method of  claim 15 , wherein the fixed dose provides from 800-1100 mg testosterone tridecanoate per day. 
     
     
         17 . The method of  claim 15 , wherein the fixed dose provides from 900-1100 mg testosterone tridecanoate per day. 
     
     
         18 . The method of  claim 15 , wherein the fixed dose provides from 925-1075 mg testosterone tridecanoate per dose. 
     
     
         19 . The method of  claim 15 , wherein the fixed dose provides from 950-1050 mg testosterone tridecanoate per dose. 
     
     
         20 . The method of  claim 15 , wherein the fixed dose provides from 975-1025 mg testosterone tridecanoate per dose. 
     
     
         21 . The method of  claim 15 , wherein the fixed dose provides from 985-1015 mg testosterone tridecanoate per day. 
     
     
         22 . The method of  claim 15 , wherein the fixed dose provides from 995-1005 mg testosterone tridecanoate per day. 
     
     
         23 . The method of  claim 15 , further comprising determining a serum testosterone level of said male patient after initiation of administration of T13. 
     
     
         24 . The method of  claim 15 , further comprising determining a serum testosterone level of said male after initiation of T13 administration, wherein unacceptably high serum testosterone levels after reaching a steady state indicates an advised discontinuation of therapy. 
     
     
         25 . The method of  claim 15 , further comprising determining a serum testosterone level of said male after initiation of T13 administration, wherein unacceptably low serum testosterone levels after reaching a steady state indicates an advised discontinuation of therapy. 
     
     
         26 . The method of  claim 15 , wherein the fixed dose provides about 1000 mg testosterone tridecanoate per day. 
     
     
         27 . The method of  claim 15 , wherein the fixed dose provides safe and efficacious testosterone replacement therapy. 
     
     
         28 . The method of  claim 15 , further comprising determining a total serum testosterone concentration, wherein a total serum testosterone concentration that consistently exceeds 1200, 1300, 1400, 1500, 1600, 1700, 1800, 1900, 2000, 2100, 2200, 2300, 2400 or 2500 ng/dL indicates an advised discontinuation of therapy. 
     
     
         29 . The method of  claim 28 , wherein a total serum testosterone concentration that consistently exceeds 2500 ng/dL indicates an advised discontinuation of therapy. 
     
     
         30 . The method of  claim 28 , wherein a total serum testosterone concentration that consistently exceeds 2100 ng/dL indicates an advised discontinuation of therapy. 
     
     
         31 . The method of  claim 28 , wherein a total serum testosterone concentration that consistently exceeds 1800 ng/dL indicates an advised discontinuation of therapy. 
     
     
         32 . The method of  claim 28 , wherein a total serum testosterone concentration that consistently exceeds 1500 ng/dL indicates an advised discontinuation of therapy. 
     
     
         33 . The method of  claim 15 , further comprising determining a total serum testosterone concentration, wherein a total serum testosterone concentration that is consistently below 300 ng/dL indicates an advised discontinuation of therapy. 
     
     
         34 . The method of  claim 15 , further comprising assessing discontinuation criteria at steady state. 
     
     
         35 . The method of  claim 15 , further comprising assessing discontinuation criteria at steady state by measuring serum testosterone concentrations. 
     
     
         36 . The method of  claim 15 , further comprising assessing discontinuation criteria at steady state by measuring serum testosterone concentrations 1 to 12 hours after administration of a fixed dose of testosterone tridecanoate. 
     
     
         37 . The method of  claim 15 , further comprising determining a hematocrit or PSA level for the patient, wherein an unacceptably high hematocrit level or an unacceptably high PSA level indicates an advised discontinuation of therapy. 
     
     
         38 . The method of  claim 15 , wherein administration of the fixed dose of T13 in the fixed dose dosing regimen provides ≥75% of patients in a population with an average serum T (C avg ) within a normal range, wherein the population comprises a group of at least 20 individuals. 
     
     
         39 . The method of  claim 15 , wherein administration of the fixed dose of T13 in the fixed dose dosing regimen provides ≥65% of patients in a population with an average serum T (C avg ) within a normal range, wherein the population comprises a group of at least 20 individuals. 
     
     
         40 . The method of  claim 15 , wherein administration of the fixed dose of T13 in the fixed dose dosing regimen provides ≥75% of patients in a population with a C max <1500 ng/dL, wherein the population comprises a group of at least 20 individuals. 
     
     
         41 . The method of  claim 15 , wherein administration of the fixed dose of T13 in the fixed dose dosing regimen provides ≥90% of patients in a population with a C max <1800 ng/dL, wherein the population comprises a group of at least 20 individuals. 
     
     
         42 . The method of  claim 15 , wherein administration of the fixed dose of T13 in the fixed dose dosing regimen provides ≥95% of patients in a population with a C max <2500 ng/dL, wherein the population comprises a group of at least 20 individuals.