Pharmacokinetic Study of Oral Testosterone (T) Ester Formulations in Hypogonadal Men

Study Overview
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Brief Summary
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The purpose of this pharmacokinetic study is to determine whether oral testosterone (T) ester formulations can be used effectively to treat men with low testosterone.

Detailed Description
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Determination of the steady-state serum T pharmacokinetic profiles for two oral formulations of T-esters [testosterone undecanoate (TU) and TU combined with testosterone enanthate (TE)] administered bis in die (BID) to 29 hypogonadal adult male subjects. TU was evaluated in total daily doses of 400 and 600 mg equivalents of T given twice daily for 7 or 8 days; TU + TE was evaluated in total daily doses of 600 and 800 mg equivalents of T given twice daily for 7 days. All subjects were enrolled into a single group and proceeded through the four Treatment Periods 1-4 in a sequential manner. In Treatment Period 3 the effect of food on the study-state pharmacokinetics profile of the TU formulation was evaluated.

Official Title
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Phase II, Repeat Dose, Pharmacokinetic Study of Oral Testosterone Ester Formulations in Hypogonadal Men

Conditions
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Hypogonadism

Intervention / Treatment
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* Drug: Oral testosterone undecanoate (TU) (300 mg T equivalents/dose)
* Drug: Oral testosterone undecanoate (TU) combined with testosterone enanthate (TE) (400 mg T equivalents/dose)
* Drug: Oral testosterone undecanoate (TU) (200 mg T equivalents/dose with and without food)
* Drug: Oral testosterone undecanoate (TU) combined with testosterone enanthate (TE) (300 mg T equivalents/dose)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male, ages 18-68 Serum total T less than or equal to 275 ng/dL Exclusion Criteria: Significant intercurrent disease of any type, in particular, liver, kidney or heart disease, uncontrolled diabetes mellitus or psychiatric illness. Abnormal prostate digital rectal examination, elevated prostate-specific antigen (PSA), American Urological Association (AUA) symptom score of >15, and/or history of prostate cancer. Hematocrit of <35 or >50% Body mass index (BMI) >36 Serum transaminases > 2 times upper limit of normal or serum bilirubin > 2.0 mg/dL

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 68 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
Intervention Model: Single Group Assignment
Interventional Model Description: All subjects were enrolled into a single group and proceeded through the four Treatment Periods 1-4 in a sequential manner.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: All study participants<br>Treatment Period 1: Three capsules each containing 100 mg testosterone (T) as testosterone undecanoate (TU), twice daily (BID) for 7 days. Treatment Period 2: Two capsules each containing 200 mg T as TU and testosterone enanthate (TE), BID for 7 days. Treatment Period 3: Two capsules each containing 100 mg T as TU, BID for 8 days. Treatment Period 4: Two capsules each containing 150 mg T as TU and TE, BID for 7 days. | Drug: Oral testosterone undecanoate (TU) (300 mg T equivalents/dose)<br>* Three capsules each containing 100 mg testosterone (T) as TU, BID. 300 mg T equivalents BID 30 minutes after initiation of breakfast and dinner meals for 7 days. A 7-14 day washout period occurred between successive Treatment Periods.<br>Drug: Oral testosterone undecanoate (TU) combined with testosterone enanthate (TE) (400 mg T equivalents/dose)<br>* Two capsules each containing 100 mg T as TU and 100 mg T as TE, BID. 400 mg T equivalents BID 30 minutes after initiation of breakfast and dinner meals for 7 days. A 7-14 day washout period occurred between successive Treatment Periods.<br>Drug: Oral testosterone undecanoate (TU) (200 mg T equivalents/dose with and without food)<br>* Two capsules each containing 100 mg T as TU, BID for 8 days. 200 mg T equivalents BID 30 minutes after initiation of meals (breakfast and dinner), except for Day 8 when the morning dose was administered fasting. A 7-14 day washout period occurred between successive Treatment Periods.<br>Drug: Oral testosterone undecanoate (TU) combined with testosterone enanthate (TE) (300 mg T equivalents/dose)<br>* Two capsules each containing 150 mg T as TU and 150 mg T as TE, BID. 300 mg T equivalents BID 30 minutes after initiation of breakfast and dinner meals for 7 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Testosterone Average Concentration (Cavg) (ng/dL) | Sampling to determine serum T Cavg post AM and PM doses and for 24 hours in Treatment Periods 1, 2, and 4. Sampling to determine serum T Cavg post AM dose with food (Day 7) and fasting (Day 8) in Treatment Period 3. | 30 minutes pre-dose and 0, 1, 2, 4, 8, 12 hours and 0,1, 2, 4, 8, and 12 hours post respective AM/PM doses | 
| Serum Testosterone Area Under Curve (AUC) (0-24) (ng•hr/dL) | Sampling to determine serum T AUC post AM and PM doses and for 24 hours in Treatment Periods 1, 2, and 4. Sampling to determine serum T AUC with food (Day 7) and fasting (Day 8) in Treatment Period 3. | 30 minutes pre-dose and 0, 1, 2, 4, 8, 12 hours and 0,1, 2, 4, 8, and 12 hours post respective AM/PM doses | 

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