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

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

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

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.

Inclusion Criteria:

1. Secondary hypogonadal males between the ages of 18 and 65
2. Men currently using topical testosterone products should wash-out for at least 7 days before Visit 1.
3. All clinical laboratory tests within normal ranges (any clinically significant deviation of laboratory results will require approval of sponsor)
4. 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
5. LH < 15mIU/mL (at Visit 1 only)
6. Ability to complete the study in compliance with the protocol
7. Ability to understand and provide written informed consent.

Exclusion Criteria:

1. 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).
2. Use testosterone injection, 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 based on the Investigator's assessment at baseline. Subjects treated for Type II diabetes will be allowed into the study.
5. A hematocrit ≥ 51% or a hemoglobin ≥ 17 g/dL
6. Clinically significant abnormal findings on screening examination, based on the Investigator's assessment.
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. 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
11. Irreversibly infertile or compromised fertility (cryptorchism, Kallman Syndrome, primary hypogonadism, or tumors of the pituitary)
12. Current or history of breast cancer
13. Current or history of prostate cancer or a suspicion of prostate disease unless ruled out by prostate biopsy, or a PSA > 3.6
14. Presence or history of known hyperprolactinemia with or without a tumor
15. Chronic use of medications use such as glucocorticoids
16. Chronic use of narcotics
17. Subjects know to be positive for HIV
18. End stage renal disease
19. Subjects with cystic fibrosis (mutation of the CFTR gene)
20. Enrollment in a previous Androxal study