Phase III Study to Evaluated Morning Testosterone Normalization in Men With Secondary Hypogonadism

NCT ID: NCT01532414

Last Updated: 2015-05-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 151 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-08-31
• Study Completion Date: 2013-03-31

Brief 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.

Detailed Description

Protocol ZA-301 is a randomized, double-blind, placebo-controlled multi-center Phase 3 study to evaluate normalization of morning testosterone levels in overweight men with acquired hypogonadotropic hypogonadism and normal baseline sperm concentrations. The study requires 10 to 12 clinic visits (2 for eye exams), and is approximately 4 to 5½ months in duration. Subjects will be treated for 12-18 weeks. At Visit 3 (Week 6) subjects who do not achieve morning T values ≥300 ng/dL will be up-titrated to 25 mg. Placebo subjects may be sham titrated. Up-titrated subjects will receive an additional 6 weeks of treatment (18 weeks total). A schedule of procedures and assessments is displayed in Section 4. The study will enroll up to 152 male subjects, up to 114 randomized to treatment with Androxal and up to 38 randomized to placebo, in a 3:1 ratio. Subjects must not have used any prior testosterone treatments within the last 6 months.

Eligible subjects must have 2 consecutive assessments of morning T below 300 ng/dL and LH below 9.4 mIU/mL. They will provide 2 sperm samples at baseline, at least 2 days apart, another 2 after 12 weeks of treatment, and up-titrated subjects will provide an additional 2 samples at the end of treatment. After 12 weeks of treatment (V5) all subjects will undergo serial T assessment for determination of the Cavg. Safety assessments will include collection of adverse events, eye examinations, physical examinations and clinical laboratory assessments.

Conditions

Secondary Hypogonadism

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Androxal 12.5 mg

Androxal (enclomiphene citrate), 12.5 mg oral capsules taken once daily

Group Type: EXPERIMENTAL

Androxal

Intervention Type: DRUG

oral, capsules, taken one time daily, for 3 months

Androxal 25 mg

Androxal (enclomiphene citrate), 25 mg oral capsules taken once daily

Group Type: EXPERIMENTAL

Androxal

Intervention Type: DRUG

oral, capsules, taken one time daily, for 3 months

Placebo

Placebo oral capsules taken one time daily

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Oral capsule taken one time daily for 3 months

Interventions

Androxal

oral, capsules, taken one time daily, for 3 months

Intervention Type: DRUG

Placebo

Oral capsule taken one time daily for 3 months

Intervention Type: DRUG

Other Intervention Names

Enclomiphene citrate; Dummy

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Repros Therapeutics Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Joseph S Podolski

Role: STUDY_DIRECTOR

Repros Therapeutics

Locations

Coastal Clinical Research

Mobile, Alabama, United States

Baptist Health Center for Clinical Research

Little Rock, Arkansas, United States

SC Clinical Research

Garden Grove, California, United States

Mission Internal Medicine Group

Mission Viejo, California, United States

Rancho Cucamonga Clinical Trials

Rancho Cucamonga, California, United States

San Diego Sexual Medicine

San Diego, California, United States

West Coast Clinical Research

Tarzana, California, United States

Florida Fertility Institute

Clearwater, Florida, United States

Tampa Bay Medical Research

Clearwater, Florida, United States

ALL Medical Research

Cooper City, Florida, United States

Clinical Research of South Florida

Coral Gables, Florida, United States

Therafirst Medical Center

Fort Lauderdale, Florida, United States

Well Pharma Medical Research Group

Miami, Florida, United States

Phase One Solutions

Miami Gardens, Florida, United States

Meridien Research

St. Petersburg, Florida, United States

Central Kentucky Research Associates

Lexington, Kentucky, United States

Clinical Research Advantage

Henderson, Nevada, United States

Premier Urology Associates

Lawrenceville, New Jersey, United States

Rochester Clinical Research

Rochester, New York, United States

Coastal Carolina Research Center

Mt. Pleasant, South Carolina, United States

New Orleans Center for Clinical Research

Knoxville, Tennessee, United States

Lone Peak Family Medicine

Draper, Utah, United States

Granger Medical Clinic

West Valley City, Utah, United States

Countries

United States

Related Links

http://www.reprosrx.com

Sponsor home page

Other Identifiers

ZA-301

Identifier Type: -

Identifier Source: org_study_id