Normalization of Morning Testosterone Levels in Men With Secondary Hypogonadism

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Secondary Hypogonadism

Intervention / Treatment
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* Drug: Placebo
* Drug: topical testosterone
* Drug: Androxal


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 |