Normalization of Morning Testosterone Levels in Men With Secondary Hypogonadism

A Randomized, Double Blind, Placebo and Active Controlled, Parallel, Multi-Center Phase IIb Study to Evaluate Normalization of Morning Testosterone Levels in Men With Secondary Hypogonadism

The Purpose of the study is to determine the effects of Androxal on morning testosterone and reproductive status in men with secondary hypogonadism(confirmed morning Testosterone less than 250 ng/dL), compared to changes with placebo, or Testim (topical testosterone). The effects of Testim versus placebo on reproductive status will also be examined. Study subjects must not be currently using a topical testosterone.

Study Overview

• Status: Completed
• Conditions: Secondary Hypogonadism
• Intervention / Treatment: Drug: Placebo; Drug: topical testosterone; Drug: Androxal

Detailed Description

This study is a phase IIb, 4 arm study with three month active dosing period. Three of the four treatment groups will be randomized to either Androxal or placebo in a double-blind fashion, and the fourth treatment group will receive open-label Testim. The doses of Androxal in the blinded portion of the study will be 12.5 mg and 25 mg, in capsule form.

• Study Type: Interventional
• Enrollment (Actual): 83
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Garden Grove, California, United States, 92844
      • Paradigm Clinical Inc.
    • Sacramento, California, United States, 95831
      • Northern California Research Corp
    • San Diego, California, United States, 92108
      • Medical Center for Clinical Research
    • Torrance, California, United States, 90502
      • Los Angeles Biomedical Research Institute
  • Nevada
    • Las Vegas, Nevada, United States, 89109
      • Affiliated Clinical Research
    • Las Vegas, Nevada, United States, 89144
      • Affiliated Clinical Research Inc.
  • New York
    • Great Neck, New York, United States, 11021
      • Weill Cornell Medical College and Smith Institute
    • New York, New York, United States, 10022
      • Natan Bar-Chama
    • New york, New York, United States, 10016
      • Jed Kaminetsky
    • Purchase, New York, United States, 10577
      • Michael A Werner
  • Texas
    • Austin, Texas, United States, 78758
      • Discovery Clinical Trials
    • Carrollton, Texas, United States, 75010
      • Research Across America
    • Houston, Texas, United States, 77062
      • Centex Research
    • Houston, Texas, United States, 77095
      • Endocrine and Psychiatry Center
    • Houston, Texas, United States, 77024
      • Texas Urology Specialist
    • Hurst, Texas, United States, 76054
      • Protenium Clinical Research
    • Lake Jackson, Texas, United States, 77566
      • R/D Clinical Research
    • San Antonio, Texas, United States, 78229
      • Cetero Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy males between the ages of 21 and 65 years of age
• All clinical laboratory tests within normal ranges (any clinically significant deviation of laboratory results will require approval of sponsor)
• Previously or concurrently diagnosed as having secondary hypogonadism and confirmed morning testosterone <250ng/dL (two assessments at least 10 days apart)
• Ability to complete the study in compliance with the protocol
• Ability to understand and provide written informed consent
• Agreement to use double barrier contraception if with a fertile female partner
• Agreement to provide a semen sample in the clinic

Exclusion Criteria:

• Use of an injectable, oral, topical, or subcutaneous pelleted testosterone within 6 months prior to study
• Use of spironolactone, cimetidine, Clomid, 5α-reductase inhibitors, hCG, androgen, estrogen, anabolic steroid, DHEA, or herbal hormone products during the study
• Use of Clomid in the past year
• Uncontrolled hypertension or diabetes mellitus based on the Investigator's assessment at baseline. Subjects treated for Type II diabetes but exhibiting glycemic control will be allowed into the study
• A hematocrit >50% or a hemoglobin >17 g/dL
• Clinically significant abnormal findings on screening examination
• Use of an investigational drug or product, or participation in a drug or medical device research study within 30 days prior to receiving study medication
• Known hypersensitivity to Clomid
• Symptomatic cataracts (nuclear sclerosis cataract or cortical cataract grade > 2 based on 0-4 scale or any trace of posterior subcapsular cataract)
• Any condition which in the opinion of the investigator would interfere with the participant's ability to provide informed consent, comply with study instructions, possibly confound interpretation of study results, or endanger the participant if he took part in the study
• Irreversibly infertile or compromised fertility (cryptorchism, Kallman Syndrome, primary hypogonadism, vasectomy, or tumors of the pituitary)
• Current or history of breast cancer
• Current or history of prostate cancer or a suspicion of prostate disease unless ruled out by prostate biopsy, or a PSA>3.6
• Presence or history of hyperprolactinemia with or without a tumor
• Chronic use of medications use such as glucocorticoids
• Subjects with cystic fibrosis (mutation of the CFTR gene)
• Subjects unable to provide a semen sample in the clinic
• Subject has a BMI >36 kg/m2

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo capsule 1x daily for 3 months
Experimental: Androxal 12.5 mg; Androxal 12.5 mg/day	Drug: Androxal; Capsule of either 12.5 mg or 25 mg Androxal, 1x daily for 3 months; Other Names: Enclomiphene citrate
Experimental: Androxal 25 mg; Androxal 25 mg/day	Drug: Androxal; Capsule of either 12.5 mg or 25 mg Androxal, 1x daily for 3 months; Other Names: Enclomiphene citrate
Active Comparator: Testim (topical testosterone)	Drug: topical testosterone; testosterone gel applied 1x daily for 3 months; Other Names: AndroGel; Testim

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Total Morning Testosterone	Changes in values from baseline in total morning testosterone levels at month 3 comparing Androxal 12.5 and 25 mg to placebo and Testim	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Luteinizing Hormone Levels	Changes in values from baseline in LH at month 3	3 months
Change in FSH After 3 Months of Treatment		3 months
Reproductive Safety	Change from baseline in sperm concentration	3 months

Collaborators and Investigators

• Sponsor: Repros Therapeutics Inc.
• Investigators: Principal Investigator: Larry Lipshultz, MD, Baylor College of Medicine

Publications and helpful links

General Publications

• Wiehle RD, Fontenot GK, Wike J, Hsu K, Nydell J, Lipshultz L; ZA-203 Clinical Study Group. Enclomiphene citrate stimulates testosterone production while preventing oligospermia: a randomized phase II clinical trial comparing topical testosterone. Fertil Steril. 2014 Sep;102(3):720-7. doi: 10.1016/j.fertnstert.2014.06.004. Epub 2014 Jul 17.

Helpful Links

• Sponsor website
• Website

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: January 4, 2011
• First Submitted That Met QC Criteria: January 4, 2011
• First Posted (Estimate): January 5, 2011

Study Record Updates

• Last Update Posted (Estimate): July 28, 2014
• Last Update Submitted That Met QC Criteria: June 27, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Endocrine System Diseases; Gonadal Disorders; Neoplastic Processes; Neoplasm Metastasis; Hypogonadism; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Estrogen Antagonists; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Androgens; Testosterone; Clomiphene; Enclomiphene; Zuclomiphene
• Other Study ID Numbers: ZA-203