Pilot Pharmacokinetic Study of Oral Testosterone Ester Formulations in Hypogonadal Men

Study Overview
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Brief Summary
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Determine the serum pharmacokinetic profile for two oral formulations of T-esters (one TE and one TU) administered once -(QD) and twice-daily (BID) to hypogonadal men.

Detailed Description
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Five period cross-over study in which subjects received a single day of dosing in each period. Dosing was either QD or BID with one of two T esters (T-enanthate (TE) or T-undecanoate (TU)). Dosing was within 5 minutes of meals (breakfast and for BID dosing dinner). There was a minimum of a 5-day washout between periods. Subjects were hypogonadal men.

Official Title
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Phase IIa, Pilot, Pharmacokinetic Study of Oral Testosterone Ester Formulations in Hypogonadal Men

Conditions
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Hypogonadism

Intervention / Treatment
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* Drug: Testosterone undecanoate
* Drug: Testosterone enanthate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male, ages 18 to 65 Serum total testosterone less than or equal to 250 ng/dL Naive to androgen replacement therapy Subject must be on stable doses of thyroid or adrenal replacement hormones for at least 14 days prior to enrollment Exclusion Criteria: Significant intercurrent disease of any type, in particular, liver, kidney or heart disease, uncontrolled diabetes mellitus or psychiatric illness. Patients with treated hyperlipidemia will not be excluded provided they have been stable on their lipid-lowering mediation for at least three months. For non-insulin dependent diabetic subjects, HbA1c>9%. Abnormal prostate digital rectal examination, elevated PSA (serum PSA >4ng/mL), AUA Sympton Score greater than or equal to 15 points, and a history or prostate cancer. Serum transaminases >2X upper limit of normal (ULN) or serum bilirubin >2.0 mg/dL. History of severe or multiple allergies, severe adverse drug reaction or leucopenia. Known hypersensitivity to lidocaine or all surgical dressings. History of abnormal bleeding tendencies. Oral, topical, or buccal T therapy within the previous week, or intramuscular T injection within the previous 4 week. Use of dietary supplements that may increase serum T, such as androstenedione or DHEA, within the previous 4 weeks. Know malabsorption syndrome and/or current treatment with oral lipase inhibitors, bile acid-binding resins, colestipol, fibric acid derivatives, gemfibrozil, and probucol. Smokers who are unable to refrain from smoking during confinement periods. History of, or current evidence of, abuse of alcohol or any drug substance. Poor compliers or those unlikely to attend. Receipt of any drug as part of a research study within 30 days of inital dose administration in this study. Blood donation (usually 550 mL) within the 12-week period before the initial study dose. Hematocrit less than 35%. Known clinical polycythemia or hematocrit greater than 50%. Current use of paroxetine and clomipramine, antiandrogens, estrogens, p450 enzyme inducers, or barbiturates. History of sleep apnea.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Testosterone undecanoate<br>Period 2 - 200 mg T (as TU) QD Period 3 - 200 mg T (as TU) BID (100 mg/dose) Period 4 - 400 mg T (as TU) BID (200 mg/dose) | Drug: Testosterone undecanoate<br>* Single-day dose as QD or BID for 3 of 5 crossover periods<br>* Other names: TU;|
| Active Comparator: Testosterone enanthate<br>Period 1 - 400 mg T (as TE) QD Period 5 - 800 mg T (as TE) BID (400 mg/dose) | Drug: Testosterone enanthate<br>* Single-day dose for 2 of 5 crossover periods<br>* Other names: TE;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Serum Testosterone Cavg | The objective of the study was to determine the single day serum pharmacokinetic profile for two oral formulations of T-esters (one TE and one TU formulation) administered once- and twice-daily to hypogonadal men. | Concentrations at -0.5, 0, 1, 2, 4, 8, 12, 13, 14, 16, 20, 24 and 34 hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Serum Dihydrotestosterone Cmax | The objective of the study was to determine the single day serum pharmacokinetic profile for two oral formulations of T-esters (one TE and one TU formulation) administered once- and twice-daily to hypogonadal men. | 24 hours post-dose in each period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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testosterone, male hypogonadism, low testosterone