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

A 12 Month, Single Blind, Placebo Controlled, Phase III Study to Assess the Effects of Enclomiphene Citrate Treatment On Bone Mineral Density in Men With Secondary Hypogonadism

To determine the effects of 12 months of treatment with Androxal on bone mineral density in men with secondary hypogonadism.

Study Overview

• Status: Completed
• Conditions: Effect of Treatment on Bone Mineral Density
• Intervention / Treatment: Drug: enclomiphene citrate; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 300
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Mesa, Arizona, United States, 85213
    • Phoenix, Arizona, United States, 85050
    • Tempe, Arizona, United States, 85283
  • California
    • Mission Viejo, California, United States, 92691
    • Newport Beach, California, United States, 92663
    • Rancho Cucamonga, California, United States, 91730
  • Florida
    • Clearwater, Florida, United States, 33761
    • Fort Lauderdale, Florida, United States, 33308
    • Jupiter, Florida, United States, 33458
    • Miami, Florida, United States, 33143
    • Miami Gardens, Florida, United States, 33169
  • Nevada
    • Henderson, Nevada, United States, 89052
  • New Jersey
    • Lawrenceville, New Jersey, United States, 08690
  • New York
    • New York, New York, United States, 10016
    • Rochester, New York, United States, 14609
  • Texas
    • Houston, Texas, United States, 77030
  • Utah
    • Salt Lake City, Utah, United States, 84124

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 58 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; 1 placebo capsule per day, oral
Experimental: Androxal	Drug: enclomiphene citrate; 12.5 mg, 1 capsule, daily, oral. After 6 weeks of treatment, subjects will remain on 12.5 mg/day if their morning testosterone level is greater than 300 ng/dL. If a subject's testosterone is less than 300 ng/dL, the subject's dose will be increased to 25 mg/day; Other Names: Androxal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bone Mineral Density	Change in bome mineral density at the end of study compared to placebo	52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Testosterone	Changes of values from baseline in total morning Testosterone levels at week 52.	52 weeks

Collaborators and Investigators

• Sponsor: Repros Therapeutics Inc.

Publications and helpful links

Helpful Links

• Sponsor's corporate web page

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: June 12, 2012
• First Submitted That Met QC Criteria: June 12, 2012
• First Posted (Estimate): June 14, 2012

Study Record Updates

• Last Update Posted (Estimate): October 1, 2014
• Last Update Submitted That Met QC Criteria: September 29, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Gonadal Disorders; Hypogonadism; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Estrogen Antagonists; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Clomiphene; Enclomiphene; Zuclomiphene
• Other Study ID Numbers: ZA-303