Open-label, Follow-up Study of Oral Testosterone Undecanoate in Hypogonadal Men

Study Overview
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Brief Summary
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The purpose of this one year extension (follow-up) study is to gather additional safety data in hypogonadal men treated with oral TU or AndroGel who have completed the 12-month Phase III study CLAR-09007.

Detailed Description
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This is the long-term extension of Study CLAR-09007, which like Study CLAR-09007, is an open-label study. This study contained an arm to evaluate the oral TU formulation as well as a comparator arm of the market-leading transdermal T-gel formulation. The comparator arm was included in the Phase III study and in this extension study to allow a general evaluation of comparative safety. Subjects randomized to oral TU in the Phase III study were continued on oral TU in the extension, and those who completed this 12-month Phase IV study have been followed for a total of 2 years of oral TU therapy. Likewise, subjects randomized to transdermal T-gel in the Phase III study were continued on T-gel in the extension, and those who completed this 12-month Phase IV study have been followed for a total of 2 years of T gel therapy. This 2-year period of therapy and assessments was to provide a long-term view of the safety of oral TU and the stability of the T replacement.

Official Title
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Open-Label Study of Oral Testosterone Undecanoate (TU) in Hypogonadal Men

Conditions
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Male Hypogonadism

Intervention / Treatment
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* Drug: Oral testosterone undecanoate
* Drug: Transdermal testosterone gel (AndroGel)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects were to have completed Study CLAR-09007. Subjects were to have adequate venous access in the left or right arm to allow collection of a number of blood samples via a venous cannula. Subjects were required to remain off all forms of T except for study medication throughout the entire study. Subjects voluntarily gave written informed consent to participate in this study. Subjects meeting any of the following criteria were not eligible for participation in this study: Significant intercurrent disease of any type, in particular liver, kidney, uncontrolled or poorly controlled heart disease, or psychiatric illness developed during the Phase III study that would, in the opinion of the Investigator, require exclusion from this study. Untreated, severe obstructive sleep apnea (diagnosed during previous Phase III study). Serum transaminases >2 times upper limit of normal (ULN), serum bilirubin >2.0 mg/dL and serum creatinine >2.0 mg/dL at the final visit for Study CLAR 09007. Abnormal prostate digital rectal examination (palpable nodule[s]) or elevated PSA (serum PSA >4 ng/mL) at the final visit for Study CLAR-09007. Use of dietary supplement saw palmetto or phytoestrogens and use of any dietary supplements that may increase serum T, such as androstenedione or dehydroepiandrosterone (DHEA). Known malabsorption syndrome and/or current treatment with oral lipase inhibitors (e.g., orlistat [Xenical]) and bile acid-binding resins (e.g., cholestyramine [Questran], colestipol [Colestid]). Poor compliers with study medication, study procedures, or study visits in Study CLAR 09007. Concomitant use of antiandrogens, estrogens, potent oral CYP3A4 inducers (e.g., barbiturates, glucocorticoids [pharmacologic doses of glucocorticoids for replacement therapy were not exclusionary]) and potent CYP3A4 inhibitors (e.g., human immunodeficiency virus [HIV] antivirals [indinavir, nelfinavir, ritonavir, saquinavir, delaviridine], amiodarone, azithromycin, ciprofloxacin, ketoconazole). (Note: Short-term ciprofloxacin administration completed more than 7 days prior to study visits was not exclusionary during the study.)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oral testosterone undecanoate<br>Oral testosterone undecanoate; continue dose from previous Phase III trial; 100-300 mg T (as TU), BID, for 12 months. | Drug: Oral testosterone undecanoate<br>* Total daily dose of T = 200 mg T (as 316 mg TU) to 600 mg T (as 948 mg TU), taken as 100 mg to 300 mg T BID<br>* Other names: Oral TU;|
| Active Comparator: Transdermal testosterone gel (AndroGel)<br>Transdermal testosterone gel; continue dose from previous Phase III trial, 2.5-10 g/applied once daily for 12 months | Drug: Transdermal testosterone gel (AndroGel)<br>* Total daily dose of T = 2.5 to 10 g of gel (25 mg to 100 mg T) QD<br>* Other names: AndroGel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change From Baseline in T Cholesterol | Long-term safety profile of oral TU product compared with AndroGel based on absolute change from primary baseline based on Total Cholesterol, HDL, LDL, hemoglobin, hematocrit and prostate volume. | Approximately 365 days | 
| Absolute Change From Baseline in HDL | Long-term safety profile of oral TU product compared with AndroGel based on absolute change from primary baseline based on Total Cholesterol, HDL, LDL, hemoglobin, hematocrit and prostate volume. | Approximately 365 days | 
| Absolute Change From Baseline in LDL | Long-term safety profile of oral TU product compared with AndroGel based on absolute change from primary baseline based on Total Cholesterol, HDL, LDL, hemoglobin, hematocrit and prostate volume. | Approximately 365 days | 
| Absolute Change From Baseline in Hgb | Long-term safety profile of oral TU product compared with AndroGel based on absolute change from primary baseline based on Total Cholesterol, HDL, LDL, hemoglobin, hematocrit and prostate volume. | Approximately 365 days | 
| Absolute Change From Baseline in Hct | Long-term safety profile of oral TU product compared with AndroGel based on absolute change from primary baseline based on Total Cholesterol, HDL, LDL, hemoglobin, hematocrit and prostate volume. | Approximately 365 days | 
| Absolute Change From Baseline in Prostate Volume | Long-term safety profile of oral TU product compared with AndroGel based on absolute change from primary baseline based on Total Cholesterol, HDL, LDL, hemoglobin, hematocrit and prostate volume. | Approximately 365 days |