The Effect on Androxal Versus Androgel on Morning Testosterone in Men With Secondary Hypogonadism (Low Testosterone)

Study Overview
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Brief Summary
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The study will determine the effects of three doses of Androxal(enclomiphene citrate)on morning testosterone versus AndroGel(approved topical treatment)in men with low testosterone (<350 ng/dL)after 6 weeks of continuous dosing.

Detailed Description
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Study will require 7 visits, which includes 2 overnight stays in a clinic. One visit is an eye exam. Blood samples are required at all visits including sampling every hour for a 24 hour time period during the 2 overnight stays. A six month extension study will be available for all subjects completing the 6-week study.

Official Title
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A Randomized, Single Blind, Multi-Center Phase II Study to Evaluate the Effect of Three Different Doses of Androxal and AndroGel on 24-Hour Luteinizing Hormone and Testosterone in Normal Healthy Men

Conditions
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Secondary Hypogonadism

Intervention / Treatment
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* Drug: Androxal (enclomiphene citrate)
* Drug: Testosterone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males between the ages of 18 and 65 years of age exhibiting morning testosterone ≤350 ng/dL. All clinical laboratory tests within normal ranges (any clinically significant deviation of laboratory results will require approval of sponsor) Ability to complete the study in compliance with the protocol Ability to understand and provide written informed consent Agreement to use a condom, and with a fertile female partner, another form of contraception. Agreement to provide a semen sample in the clinic Exclusion Criteria: Use of an injectable, oral, topical, or subcutaneous pelleted testosterone within 3 months prior to study Use of spironolactone, cimetidine, 5α-reductase inhibitors, hCG, androgen, estrogen, anabolic steroid, DHEA, or herbal hormone products during the study Use of Clomid in the past year or during the study 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. Newly diagnosed diabetics need to be treated for at least 48 hours before being enrolled in the study. A hematocrit ≥51 % 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 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) History of breast cancer History of prostate cancer or a suspicion of prostate disease unless ruled out by prostate biopsy, or a PSA >3.6 History of known hyperprolactinemia with or without a tumor Chronic use of medications use such as glucocorticoids Chronic use of narcotics Subjects known to be positive for HIV Subjects with end stage renal disease Subjects with cystic fibrosis (mutation of the CFTR gene) Subjects unable to provide a semen sample in the clinic Subject has a BMI >42 kg/m2

Ages Eligible for Study
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Minimum Age: 18 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Androxal 6.25 mg<br>Androxal 6.25 mg/day | Drug: Androxal (enclomiphene citrate)<br>* capsule oral 1X a day 6 weeks<br>* Other names: low testosterone therapy;|
| Experimental: Androxal 12.5 mg<br>Androxal 12.5 mg/day | Drug: Androxal (enclomiphene citrate)<br>* capsule oral 1X a day 6 weeks<br>* Other names: low testosterone therapy;|
| Experimental: Androxal 25 mg<br>Androxal 25 mg/day | Drug: Androxal (enclomiphene citrate)<br>* capsule oral 1X a day 6 weeks<br>* Other names: low testosterone therapy;|
| Active Comparator: AndroGel<br>AndroGel 5G topical testosterone | Drug: Testosterone<br>* topical gel 1X a day 6 weeks<br>* Other names: exogenous testosterone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 24 Hour Average and Maximum Testosterone Concentration | The primary efficacy endpoint will be 24-hour average (TTavg) and maximum (TTmax) testosterone concentration compared to baseline after 6 weeks of treatment. Time points (in hours after dosing) at which testosterone concentration was measured are: 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24. | Baseline and Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Leuteinizing Hormone (LH) | Changes in morning LH after continuous dosing | Baseline, Week 2, Week 4, Week 6 | 
| Change in Follicle Stimulating Hormone (FSH) | Changes in morning FSH after continuous dosing | Baseline, Week 2, Week 4, Week 6 |