Clinical trial NCT01403116: Safety and Efficacy Trial of Oral Testosterone Undecanoate (TU) in Hypogonadal Men
Official title: Phase 3, Active-Controlled, Safety and Efficacy Trial of Oral Testosterone Undecanoate (TU) in Hypogonadal Men
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Male Hypogonadism
Keywords: testosterone
male hypogonadism
low testosterone
Lead sponsor: Clarus Therapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: PharmaNet
name: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
First posted: 2011-07-27
Enrollment: 325
Sex: MALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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).

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Treated Patients With Average Serum Testosterone (T) Concentrations (Cavg) Between 300 and 1000 ng/dL
timeFrame: Following 90 days of treatment
Secondary outcomes:
measure: % of Oral TU Subjects With 24-hour Maximum Serum T Concentrations (Cmax) Greater Than 1500 ng/dL on Day 90
timeFrame: 90 days
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Clinical Therapeutics, Inc.
state: Alabama
city: Birmingham
country: United States
facility: Alabama Internal Medicine, PC
state: Alabama
city: Calera
country: United States
facility: Alabama Clinical Therapeutics
state: Alabama
city: Huntsville
country: United States
facility: Medical Affliated Research Center, Inc.
state: Alabama
city: Tucson
country: United States
facility: Quality of Life Medical and Research Centers, LLC
state: Arizona
city: Burbank
country: United States
facility: Providence Clinical Research
state: California
city: Laguna Hills
country: United States
facility: South Orange County Endocrinology
state: California
city: Los Angeles
country: United States
facility: Tower Urology
state: California
city: Los Angeles
country: United States
facility: David Geffen School of Medicine
state: California
city: Torrance
country: United States
facility: Harbor-UCLA Medical Center, LA Biomedical Research Institute
state: California
city: Middlebury
country: United States
facility: Connecticut Clinical Research Center/ConnecTrials
state: Connecticut
city: New Haven
country: United States
facility: University of CT School of Medicine
state: Connecticut
city: Aventura
country: United States
facility: South Florida Medical Research
state: Florida
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Boston University School of Medicine
state: Massachusetts
city: Brooklyn
country: United States
facility: Maimonides Medical Center
state: New York
city: Great Neck
country: United States
facility: Bruce R. Gilbert, MD, PhD
state: New York
city: New York
country: United States
facility: University Urology Associates
state: New York
city: Purchase
country: United States
facility: Michael A. Werner, MD, PC
state: New York
city: Medford
country: United States
facility: Sunstone Medical Research
state: Oregon
city: Bala-Cynwyd
country: United States
facility: Urologic Consultants of Southeast Pennsylvania
state: Pennsylvania
city: Carrollton
country: United States
facility: Research Across America
state: Texas
city: Dallas
country: United States
facility: Research Across America
state: Texas
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Bonn
country: Germany
facility: University of Bonn, Clinic for Dermatology and Allergy
city: Halle
country: Germany
facility: University of Halle, Center for Reproduction and Androlgoy
city: Leipzig
country: Germany
facility: Praxis Dr. Szymula
city: Markkleeberg
country: Germany
facility: Praxis Dr. Schulze
city: Muenster
country: Germany
facility: University of Muenster, Center for Reproduction and Andrology
Study officials:
affiliation: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
name: Ronald Swerdloff, MD
role: PRINCIPAL_INVESTIGATOR
References: