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

Secondary Hypogonadism Clinical Trial

Official title:

A Randomized, Double Blind, Placebo Controlled Multi-Center Phase III Study to Evaluate Normalization of Morning Testosterone Levels in Overweight Men With Acquired Hypogonadotropic Hypogonadism and Normal Sperm Concentration

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01532414
• Other study ID #: ZA-301
• Status: Completed
• Phase: Phase 3
• First received: February 9, 2012
• Last updated: May 7, 2015
• Start date: August 2012
• Est. completion date: March 2013

Study information

• Verified date: May 2015
• Source: Repros Therapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 151
• Est. completion date: March 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 60 Years

Eligibility

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, 5a-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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypogonadism
• Neoplasm Metastasis
• Secondary Hypogonadism

Intervention

Drug:
• Androxal
oral, capsules, taken one time daily, for 3 months
• Placebo
Oral capsule taken one time daily for 3 months

Locations

Country	Name	City	State
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	Lone Peak Family Medicine	Draper	Utah
United States	Therafirst Medical Center	Fort Lauderdale	Florida
United States	SC Clinical Research	Garden Grove	California
United States	Clinical Research Advantage	Henderson	Nevada
United States	New Orleans Center for Clinical Research	Knoxville	Tennessee
United States	Premier Urology Associates	Lawrenceville	New Jersey
United States	Central Kentucky Research Associates	Lexington	Kentucky
United States	Baptist Health Center for Clinical Research	Little Rock	Arkansas
United States	Well Pharma Medical Research Group	Miami	Florida
United States	Phase One Solutions	Miami Gardens	Florida
United States	Mission Internal Medicine Group	Mission Viejo	California
United States	Coastal Clinical Research	Mobile	Alabama
United States	Coastal Carolina Research Center	Mount Pleasant	South Carolina
United States	Rancho Cucamonga Clinical Trials	Rancho Cucamonga	California
United States	Rochester Clinical Research	Rochester	New York
United States	San Diego Sexual Medicine	San Diego	California
United States	Meridien Research	St. Petersburg	Florida
United States	West Coast Clinical Research	Tarzana	California
United States	Granger Medical Clinic	West Valley City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Repros Therapeutics Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion (Percentage) of Androxal Treated Subjects With Testosterone in the Normal Range	Proportion of pooled Androxal subjects with average serum concentration (Cavg) for T in the normal range (300 - 1040 ng/dL) after 12 weeks of treatment. Cavg will be calculated as the numerical average of 24-hour serial testosterone assessments at 0, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours after dosing.; If the lower limit of the 95% confidence interval for the Androxal treatment group at Week 12 is at least 67%, then the co-primary endpoint based on the Cavg for testosterone has been achieved.; FDA specified primary endpoint did not include comparison to placebo, thus the proportion of placebo subjects with average serum concentration (Cavg) for T in the normal range (300 - 1040 ng/dL) after 12 weeks of treatment was not calculated.	3 months	No
Primary	Subjects With 50% or Greater Decrease in Sperm Concentration Comparison of Proportion of Subjects With 50% or Greater Decrease in Sperm	Proportion of subjects with a 50% or greater decrease in sperm concentration from baseline after 12 weeks of treatment in Androxal treated subjects to placebo.; The difference between the proportions (placebo minus Androxal) and corresponding 95% confidence interval was determined and compared to the equivalence limit of -20%. If the lower limit of the 95% confidence interval was greater than -20%, then Androxal would be concluded to be non-inferior to placebo in causing a 50% reduction in sperm concentrations.	3 months	Yes

External Links

•   Sponsor home page