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.

Study Overview

• Status: Completed
• Conditions: Male Hypogonadism
• Intervention / Treatment: Drug: Oral testosterone undecanoate; Drug: topical testosterone gel

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).

• Study Type: Interventional
• Enrollment (Actual): 325
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Bonn, Germany
    • University of Bonn, Clinic for Dermatology and Allergy
  • Halle, Germany
    • University of Halle, Center for Reproduction and Androlgoy
  • Leipzig, Germany
    • Praxis Dr. Szymula
  • Markkleeberg, Germany
    • Praxis Dr. Schulze
  • Muenster, Germany
    • University of Muenster, Center for Reproduction and Andrology
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35235
      • Alabama Internal Medicine, PC
    • Birmingham, Alabama, United States, 35235
      • Alabama Clinical Therapeutics, Inc.
    • Calera, Alabama, United States, 35040
      • Alabama Clinical Therapeutics
    • Huntsville, Alabama, United States, 35801
      • Medical Affliated Research Center, Inc.
  • Arizona
    • Tucson, Arizona, United States, 85712
      • Quality of Life Medical and Research Centers, LLC
  • California
    • Burbank, California, United States, 91505
      • Providence Clinical Research
    • Laguna Hills, California, United States, 92653
      • South Orange County Endocrinology
    • Los Angeles, California, United States, 90048
      • Tower Urology
    • Los Angeles, California, United States, 90095
      • David Geffen School of Medicine
    • Torrance, California, United States, 90502
      • Harbor-UCLA Medical Center, LA Biomedical Research Institute
  • Connecticut
    • Middlebury, Connecticut, United States, 06762
      • Connecticut Clinical Research Center/ConnecTrials
    • New Haven, Connecticut, United States, 06511
      • University of CT School of Medicine
  • Florida
    • Aventura, Florida, United States, 33180
      • South Florida Medical Research
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston University School of Medicine
  • New York
    • Brooklyn, New York, United States, 11235
      • Maimonides Medical Center
    • Great Neck, New York, United States, 11021
      • Bruce R. Gilbert, MD, PhD
    • New York, New York, United States, 10016
      • University Urology Associates
    • Purchase, New York, United States, 10577
      • Michael A. Werner, MD, PC
  • Oregon
    • Medford, Oregon, United States, 97504
      • Sunstone Medical Research
  • Pennsylvania
    • Bala-Cynwyd, Pennsylvania, United States, 19004
      • Urologic Consultants of Southeast Pennsylvania
  • Texas
    • Carrollton, Texas, United States, 75010
      • Research Across America
    • Dallas, Texas, United States, 75234
      • Research Across America
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oral testosterone undecanoate (TU); Treatment Period 1: 100 mg capsules, BID, with food Treatment Period 2: One of the following dosages: 100 mg BID; 150 mg BID; 100 mg BID; 100 mg and 150 mg BID; 150 mg capsules BID Safety Follow-up Phase: Initial dose: ~84 doses Maintenance dose-Titrated dose: ~96 doses Safety follow-up at maintenance dose: ~540 doses	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.; Other Names: Oral TU
Active Comparator: topical testosterone gel; Treatment Period 1: 5 g of 1% transdermal T-gel applied QD Treatment Period 2: 2.5 g of 1% transdermal T-gel applied QD; 5 g of 1% transdermal T-gel applied QD; 7.5 g of 1% transdermal T-gel applied QD; 10 g of 1% transdermal T-gel applied QD Safety Follow-up Phase: Initial dose: ~42 doses Maintenance dose-Titrated dose: ~48 doses Safety follow-up at maintenance dose: ~270 doses	Drug: 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.; Other Names: T-gel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
% 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

Collaborators and Investigators

• Sponsor: Clarus Therapeutics, Inc.
• Collaborators: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center; PharmaNet
• Investigators: Principal Investigator: Ronald Swerdloff, MD, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): September 1, 2013
• Study Completion (Actual): September 1, 2013

Study Registration Dates

• First Submitted: July 25, 2011
• First Submitted That Met QC Criteria: July 25, 2011
• First Posted (Estimate): July 27, 2011

Study Record Updates

• Last Update Posted (Actual): August 14, 2018
• Last Update Submitted That Met QC Criteria: July 16, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: testosterone; male hypogonadism; low testosterone
• Additional Relevant MeSH Terms: Endocrine System Diseases; Gonadal Disorders; Hypogonadism; Physiological Effects of Drugs; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Androgens; Anabolic Agents; Testosterone; Methyltestosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate
• Other Study ID Numbers: CLAR-09007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: No plan to share IPD