Clinical trial NCT01532414: Phase III Study to Evaluated Morning Testosterone Normalization in Men With Secondary Hypogonadism
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Secondary Hypogonadism
Lead sponsor: Repros Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2012-02-14
Enrollment: 151
Sex: MALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Proportion (Percentage) of Androxal Treated Subjects With Testosterone in the Normal Range
timeFrame: 3 months
measure: Subjects With 50% or Greater Decrease in Sperm Concentration Comparison of Proportion of Subjects With 50% or Greater Decrease in Sperm
timeFrame: 3 months
Secondary outcomes:
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Coastal Clinical Research
state: Alabama
city: Little Rock
country: United States
facility: Baptist Health Center for Clinical Research
state: Arkansas
city: Garden Grove
country: United States
facility: SC Clinical Research
state: California
city: Mission Viejo
country: United States
facility: Mission Internal Medicine Group
state: California
city: Rancho Cucamonga
country: United States
facility: Rancho Cucamonga Clinical Trials
state: California
city: San Diego
country: United States
facility: San Diego Sexual Medicine
state: California
city: Tarzana
country: United States
facility: West Coast Clinical Research
state: California
city: Clearwater
country: United States
facility: Florida Fertility Institute
state: Florida
city: Clearwater
country: United States
facility: Tampa Bay Medical Research
state: Florida
city: Cooper City
country: United States
facility: ALL Medical Research
state: Florida
city: Coral Gables
country: United States
facility: Clinical Research of South Florida
state: Florida
city: Fort Lauderdale
country: United States
facility: Therafirst Medical Center
state: Florida
city: Miami Gardens
country: United States
facility: Phase One Solutions
state: Florida
city: Miami
country: United States
facility: Well Pharma Medical Research Group
state: Florida
city: St. Petersburg
country: United States
facility: Meridien Research
state: Florida
city: Lexington
country: United States
facility: Central Kentucky Research Associates
state: Kentucky
city: Henderson
country: United States
facility: Clinical Research Advantage
state: Nevada
city: Lawrenceville
country: United States
facility: Premier Urology Associates
state: New Jersey
city: Rochester
country: United States
facility: Rochester Clinical Research
state: New York
city: Mount Pleasant
country: United States
facility: Coastal Carolina Research Center
state: South Carolina
city: Knoxville
country: United States
facility: New Orleans Center for Clinical Research
state: Tennessee
city: Draper
country: United States
facility: Lone Peak Family Medicine
state: Utah
city: West Valley City
country: United States
facility: Granger Medical Clinic
state: Utah
Study officials:
affiliation: Repros Therapeutics
name: Joseph S Podolski
role: STUDY_DIRECTOR
References: