Safety and Efficacy Trial of Oral Testosterone Undecanoate (TU) in Hypogonadal Men

Phase 3, Active-Controlled, Safety and Efficacy Trial of Oral Testosterone Undecanoate (TU) in Hypogonadal Men

The purpose of this study is to determine the safety and efficacy of an oral testosterone undecanoate formulation for use as testosterone-replacement therapy in men with low testosterone.

This was a randomized, open-label, 2-arm, active controlled, 12-month study of Oral TU that planned to enroll ≈ 300 hypogonadal men (≈ 150/group) at multiple study sites. Incorporated in the design was dose titration based on serum T concentration assessed 4-6 hrs post AM dose. Following a 2-visit screening period during which a serum T concentration was measured, eligible subjects were randomized to either Oral TU (Group A) or transdermal T-gel (Group B) for dosing during Treatment Period 1 (Days 0 to 42). Group A was initially dosed with 400 mg T daily (two 100 mg capsules, orally, twice a day [BID]), and Group B was initially dosed with 5 g of transdermal 1% T-gel.

Serum T sampling was done on Day 30, 4-6 hours after the morning dose and these T concentration results were used to determine the need for dose titration. Dose titration occurred on Day 42 for Treatment Period 2, until Day 90. Subjects whose dose was titrated on Day 42 were re-evaluated on Day 60 , with dose adjustments made as necessary on Day 74.

Serum T sampling was performed on Day 90, for Oral TU subjects who had dose titration on Day 74, on Day 105. If the serum T level was > 1800 ng/dL, the sample was repeated; subjects were discontinued if the second assayed T concentration was > 1800 ng/dL. An additional dose titration was done for subjects whose Day 180 occurred after a protocol amendment. Subjects taking 150 mg T BID with serum T over 1500 ng/dL on two separate draws were discontinued.

Safety measures included physical examination, vital signs, fasting laboratory analysis (hematology, chemistry, urinalysis), CV biomarker monitoring [hs-CRP, Lp-PLA2, Lp(a), and ApoA1], measurement of sex hormone binding globulin (SHBG); luteinizing hormone (LH), follicle-stimulating hormone (FSH); prostate specific antigen (PSA), and the American Urological Association/International Prostate Symptom Score (AUA/I-PSS).

Inclusion Criteria:

• Serum testosterone of less than or equal to 300 ng/dL on two occasions within one week (may wash out from previous oral, topical or buccal testosterone therapy)

Exclusion Criteria:

• Significant intercurrent disease of any type, in particular liver, kidney, uncontrolled or poorly controlled heart disease, or psychiatric illness
• Recent history of stroke, not including transient ischemic attack
• Untreated, sever obstructive sleep apnea.
• Hematocrit <35% or >48
• Serum transaminases >2 times upper limit of normal, serum bilirubin > 2.0 mg/dL and serum creatinine > 2.0 mgk/dL
• BMI > or equal to 36
• Stable doses of lipid-lowering medication for less than 3 months
• Stable doses of oral medication for diabetes for less than 2 months
• Abnormal prostate DRE [palpable nodule(s)], elevated PSA (>4 ng/mL), IPSS score > or equal to 19 points.
• History of breast cancer
• Use of dietary supplement saw palmetto or phytoestrogens and use of any dietary supplements that may increase serum testosterone within previous 4 weeks
• Known malabsorption syndrome and/or current treatment with oral lipase inhibitors
• History of abuse of alcohol or any drug substance within the previous 2 years
• Current use of antiandrogens, estrogens, oral CYP3A4 inducers or inhibitors, or long-acting opioid analgesics
• Receipt of any drug as part of a research study within 30 days of initial dose administration in this study.
• Blood donation within the 12 week period before the initial study dose.