Assessment of the Effects of Enclomiphene Citrate on Bone Mineral Density in Men With Secondary Hypogonadism

This study is a phase III single-blind placebo-controlled safety study with a 52 week active
dosing period with Androxal. Safety will be assessed by physical and visual acuity exams,
slit lamp and fundoscopy eye exams, clinical laboratory tests, DEXA scanning, lean soft
tissue assessment (LST), and adverse event reporting. Results will be compared to an
age-matched placebo group.

Inclusion Criteria:

1. Overweight (BMI 25 to 42 kg/m2 inclusive, or BMI 23 to 42 inclusive in Asian
subjects) males age 18 to 60 inclusive

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 <300ng/dL measured twice on separate days. One of the two
TT levels must be confirmed at baseline. Subjects who fail this criterion will be
enrolled in the placebo group.

5. LH <9.4 mIU/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 or pelleted testosterone within 6 months prior to study (men
currently on topical products may be enrolled in the study after a 7-day washout
period)

2. Use of 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 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), based on the
Investigator's assessment.

6. A hematocrit >54% or a hemoglobin >17 g/dL

7. Clinically significant abnormal laboratory findings at baseline (Visit 2), based on
the Investigator's assessment

8. 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.

9. Known hypersensitivity to Clomid

10. Symptomatic cataracts (nuclear sclerosis cataract or cortical cataract grade > 2
based on 0-4 scale or any trace of posterior subcapsular cataract)

11. Abnormal fundoscopy exam such as central retinal vein occlusion

12. 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

13. Irreversibly infertile or compromised fertility (cryptorchism, Kallman Syndrome,
primary hypogonadism, or tumors of the pituitary)

14. Current or history of breast cancer

15. Subjects with a Z-score of <2

16. Hyperparathyroidism, metabolic bone disease, previous fracture of the spine, recent
chemotherapy, use of medications that may influence BMD (thyroid replacement therapy,
immunosuppressive therapy, prednisone or antiepileptic drugs

17. No intravenous or oral contrast agents within 7 days.

18. Subject weighs >300 pounds (>136 kg)

19. Current or history of prostate cancer or a suspicion of prostate disease unless ruled
out by prostate biopsy, or a PSA>3.6

20. Presence or history of known hyperprolactinemia with or without a tumor

21. Chronic use of medications use such as glucocorticoids

22. History of drug abuse or chronic narcotic use including methadone

23. Subjects with known history of HIV and/or Hepatitis C

24. Subjects with end stage renal disease

25. Subjects with cystic fibrosis (mutation of the CFTR gene)

26. Enrollment in a previous Androxal study