Safety Study of Enclomiphene Citrate in the Treatment of Men With Secondary Hypogonadism

Study Overview
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Brief Summary
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ZA-300 is meant to determine the safety profile of Androxal (enclomiphene citrate) in men with secondary hypogonadism.

Detailed Description
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This study is a phase III, open label safety study with a six month active dosing period. All subjects will be started at 12.5 mg Androxal and titrated to 25 mg if needed. Safety will be assessed by physical and visual acuity exams, slit lamp eye exams, clinical laboratory tests and adverse event reporting.

Official Title
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An Open Label, Escalating Dose, 6 Month Phase III Safety Study Of Enclomiphene Citrate in the Treatment of Men With Secondary Hypogonadism

Conditions
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Secondary Hypogonadism

Intervention / Treatment
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* Drug: Androxal


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Secondary hypogonadal males between the ages of 18 and 65 Men currently using topical testosterone products should wash-out for at least 7 days before Visit 1. 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 with morning testosterone level < 350 ng/dL for men age < 55 and < 300ng/dl for men age 55-65 LH < 15mIU/mL (at Visit 1 only) Ability to complete the study in compliance with the protocol Ability to understand and provide written informed consent. Exclusion Criteria: Use of an injectable pelleted testosterone within 6 months prior to study (men currently on topical testosterone products may be enrolled in the study after a 7-day washout period). Use testosterone injection, 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 based on the Investigator's assessment at baseline. Subjects treated for Type II diabetes will be allowed into the study. A hematocrit ≥ 51% or a hemoglobin ≥ 17 g/dL Clinically significant abnormal findings on screening examination, based on the Investigator's assessment. 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, 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 known hyperprolactinemia with or without a tumor Chronic use of medications use such as glucocorticoids Chronic use of narcotics Subjects know to be positive for HIV End stage renal disease Subjects with cystic fibrosis (mutation of the CFTR gene) Enrollment in a previous Androxal study

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Androxal 12.5 mg<br>Androxal 12.5 mg daily | Drug: Androxal<br>* Androxal, oral, 12.5 mg capsule, taken once daily. Dose may be increased from 12.5 mg to 25 mg if indicated<br>* Other names: Enclomiphene citrate;|
| Experimental: Androxal 25 mg<br>Androxal 25 mg daily | Drug: Androxal<br>* Androxal, oral, 12.5 mg capsule, taken once daily. Dose may be increased from 12.5 mg to 25 mg if indicated<br>* Other names: Enclomiphene citrate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Total Morning Testosterone at 26 Weeks | Changes in values from baseline of total morning testosterone levels at Week 26 | 6 months | 
| Change From Baseline in LH | Mean change from baseline in LH at end of treatment (26 weeks) | 6 months | 
| Absolute Values of Morning Testosterone | Absolute values of morning testosterone at end of treatment (26 weeks) | 6 months | 
| Mean Change From Baseline FPG | Mean changes in Fasting Plasma Glucose from baseline to end of treatment (26 weeks) | 6 months | 
| Change From Baseline in BMI | Mean change from baseline in BMI at end of treatment (26 weeks) | 6 months | 
| Change From Baseline in FSH | Change from baseline in FSH at end of treatment (26 weeks) | 6 months |