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

Male Hypogonadism Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01403116
• Other study ID #: CLAR-09007
• Status: Completed
• Phase: Phase 3
• Start date: July 2011
• Est. completion date: September 2013

Study information

• Verified date: July 2018
• Source: Clarus Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 325
• Est. completion date: September 2013
• Est. primary completion date: September 2013
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hypogonadism
• Male Hypogonadism

Intervention

Drug:
• Oral testosterone undecanoate
Starting dose: 200 mg T (as TU) BID. Doses may be titrated up to a maximum dose of 300 mg T (as TU) BID or down to a minimum dose of 100 mg T (as TU) BID based on serum T values collected at 4-6 hours post AM dose on Days 30 and 60.
• topical testosterone gel
Starting dose: 5 g T applied once daily. Doses may be titrated up to a maximum dose of 10 g daily or down to a minimum dose of 2.5 g daily based on serum T values collected at 4-6 hours post AM dose on Days 30 and 60.

Locations

Country	Name	City	State
Germany	University of Bonn, Clinic for Dermatology and Allergy	Bonn
Germany	University of Halle, Center for Reproduction and Androlgoy	Halle
Germany	Praxis Dr. Szymula	Leipzig
Germany	Praxis Dr. Schulze	Markkleeberg
Germany	University of Muenster, Center for Reproduction and Andrology	Muenster
United States	South Florida Medical Research	Aventura	Florida
United States	Urologic Consultants of Southeast Pennsylvania	Bala-Cynwyd	Pennsylvania
United States	Johns Hopkins University	Baltimore	Maryland
United States	Alabama Clinical Therapeutics, Inc.	Birmingham	Alabama
United States	Alabama Internal Medicine, PC	Birmingham	Alabama
United States	Boston University School of Medicine	Boston	Massachusetts
United States	Maimonides Medical Center	Brooklyn	New York
United States	Providence Clinical Research	Burbank	California
United States	Alabama Clinical Therapeutics	Calera	Alabama
United States	Research Across America	Carrollton	Texas
United States	Research Across America	Dallas	Texas
United States	Bruce R. Gilbert, MD, PhD	Great Neck	New York
United States	Medical Affliated Research Center, Inc.	Huntsville	Alabama
United States	South Orange County Endocrinology	Laguna Hills	California
United States	David Geffen School of Medicine	Los Angeles	California
United States	Tower Urology	Los Angeles	California
United States	University of Louisville	Louisville	Kentucky
United States	Sunstone Medical Research	Medford	Oregon
United States	Connecticut Clinical Research Center/ConnecTrials	Middlebury	Connecticut
United States	University of CT School of Medicine	New Haven	Connecticut
United States	University Urology Associates	New York	New York
United States	Michael A. Werner, MD, PC	Purchase	New York
United States	University of Washington	Seattle	Washington
United States	Harbor-UCLA Medical Center, LA Biomedical Research Institute	Torrance	California
United States	Quality of Life Medical and Research Centers, LLC	Tucson	Arizona

Sponsors (3)

Lead Sponsor	Collaborator
Clarus Therapeutics, Inc.	Los Angeles Biomedical Research Institute, PharmaNet

Countries where clinical trial is conducted

United States,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Treated Patients With Average Serum Testosterone (T) Concentrations (Cavg) Between 300 and 1000 ng/dL	The percentages of treated subjects that had 24-hour serum testosterone (T) average concentrations (Cavg) between 300 and 1000 ng/dL	Following 90 days of treatment
Secondary	% of Oral TU Subjects With 24-hour Maximum Serum T Concentrations (Cmax) Greater Than 1500 ng/dL on Day 90	Percentage of Oral TU treated patients who reached study day 90 and had a maximum serum T concentrations (Cmax) values greater than 1500 ng/dL(objective to meet <15%).	90 days