Phase III Study to Evaluated Morning Testosterone Normalization in Men With Secondary Hypogonadism
Condition: Secondary Hypogonadism
MeSH terms: Neoplasm Metastasis; Hypogonadism
Intervention: Androxal; Placebo
Intervention description: oral, capsules, taken one time daily, for 3 months; Oral capsule taken one time daily for 3 months
Intervention MeSH terms: Enclomiphene; Clomiphene; Zuclomiphene
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 151.0
Sex: Male
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No

Summary:

      The purpose of ZA-301 is to determine the effects of Androxal on morning testosterone and
      reproductive status in younger overweight men with acquired hypogonadotropic hypogonadism
      (confirmed morning T<300 ng/dL) and normal sperm concentration, compared to changes with
      placebo. Subjects must not have previously been treated with testosterone products within the
      last 6 months.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Overweight (BMI 25 to 42 kg/m2 inclusive) males age 18 to 60 inclusive

          2. All clinical laboratory tests within normal ranges (any clinically significant
             deviation of laboratory results will require approval of sponsor)

          3. Previously or concurrently diagnosed as having secondary hypogonadism characterized as
             having 2 consecutive morning testosterone assessments < 300ng/dL, one of which must be
             confirmed at Baseline.

          4. LH < 9.4 mIU/mL (at Visit 1 only)

          5. Sperm count ≥ 15 million per milliliter (assessed twice at least 48 hours apart)

          6. Ability to complete the study in compliance with the protocol

          7. Ability to understand and provide written informed consent

          8. Agreement to provide a total of up to 6 semen sample in a sponsor-approved clinic on
             up to 6 separate occasions.

        Exclusion Criteria:

          1. Any prior use of testosterone treatments within the last 6 months

          2. Use of spironolactone, cimetidine, Clomid, 5α-reductase inhibitors, hCG, androgen,
             estrogen, anabolic steroid, DHEA, or herbal hormone products during the study

          3. Use of Clomid in the past year

          4. Uncontrolled hypertension or diabetes mellitus based on the Investigator's assessment
             at baseline. Subjects treated for Type II diabetes will be allowed into the study.
             Newly diagnosed diabetics need to be treated for at least 48 hours before being
             enrolled in the study.

          5. Clinically significant abnormal findings at Screening (Visit 1) or Baseline, based on
             the Investigator's assessment

          6. A hematocrit >54% or a hemoglobin >17 g/dL (sponsor may approve enrollment of subjects
             with hemoglobin up to 17.5 g/dL if the subject is at a location with a high elevation)

          7. 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.

          8. Known hypersensitivity to Clomid

          9. Symptomatic cataracts (nuclear sclerosis cataract or cortical cataract grade > 2 based
             on 0-4 scale or any trace of posterior subcapsular cataract)

         10. Abnormal fundoscopy exam such as central retinal vein occlusion

         11. 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

         12. Irreversibly infertile or compromised fertility (cryptorchism, Kallman Syndrome,
             primary hypogonadism, vasectomy, or tumors of the pituitary)

         13. Current or history of breast cancer

         14. Current or history of prostate cancer or a suspicion of prostate disease unless ruled
             out by prostate biopsy, or a PSA>3.6

         15. Presence or history of known hyperprolactinemia with or without a tumor

         16. Chronic use of medications such as glucocorticoids

         17. History of drug abuse or chronic narcotic use including methadone

         18. A recent history of alcoholism or illegal substance or steroid abuse (<2 years) or
             presence of moderate alcohol use (>21 drinks per week)

         19. Subjects with known history of HIV and/or Hepatitis C

         20. Subjects with end stage renal disease

         21. History of liver disease (including malignancy) or a confirmed AST or ALT >3 times the
             upper limit of normal

         22. History of myocardial infarction, unstable angina, symptomatic heart failure,
             ventricular dysrhythmia or know history of QTc interval prolongation

         23. History of cerebrovascular disease

         24. History of venous thromboembolic disease (e.g. deep vein thrombosis or pulmonary
             embolism)

         25. History of erythrocytosis or polycythemia

         26. Subjects with cystic fibrosis (mutation of the CFTR gene)

         27. Subjects unable to provide a semen sample in a sponsor-approved clinic

         28. Enrollment in a previous Androxal study