A Randomized, Double Blind, Placebo-Controlled, Multi-Center Phase III Study in Men With Acquired Hypogonadotropic Hypogonadism to Compare Changes in Testosterone and Sperm Concentration Following Treatment With 12.5 mg or 25 mg Androxal or AndroGel 1.62%

Repros Therapeutics

Status and phase: Completed; Phase 3

Conditions: Secondary Hypogonadism

Treatments: Drug: AndroGel 1.62%; Drug: Placebo Capsules; Drug: Androxal 12.5 mg or 25 mg; Drug: Placebo Gel

Study type: Interventional

Funder types: Industry

Identifiers

NCT01993212

ZA-304

Details and patient eligibility

About

This is a Randomized, Double Blind, Placebo-Controlled, Multi-Center Phase III Study in Men with Acquired Hypogonadotropic Hypogonadism to Compare Changes in Testosterone and Sperm Concentration Following Treatment with the 12.5 mg or 25 mg Androxal or AndroGel 1.62%.

Enrollment: 120 patients

Sex: Male

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Overweight (BMI 25 to 42 kg/m2 inclusive) males age 18 to 60 inclusive
• Previously or concurrently diagnosed as having secondary hypogonadism characterized as having at least 2 consecutive morning testosterone assessments < 300ng/dL, one of which must be confirmed at Baseline.
• LH < 9.4 mIU/mL (at Visit 1 only)
• Sperm concentration ≥ 15 million per milliliter (assessed at V2 and Baseline). V2 and Baseline measurements must be at least 48 hours apart.
• Ability to complete the study in compliance with the protocol
• Ability to understand and provide written informed consent
• Agreement to provide a total of at least 4 semen samples in a sponsor-approved clinic on 4 separate occasions.

Exclusion criteria

• Any prior use of testosterone treatments (injectable, pelleted, transdermal or sublingual) within the last 6 months
• Use of spironolactone, cimetidine, Clomid, 5α-reductase inhibitors, hCG, androgen, estrogen, anabolic steroid, DHEA, or herbal hormone products during the study
• Use of Clomid in the past year
• Any clinically significant laboratory abnormality that does not have prior written sponsor approval. If the sponsor approves subject enrollment, this will not be considered to be a protocol deviation.
• 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, if considered clinically stable by the investigator. Newly diagnosed diabetics need to be treated for at least 48 hours before being enrolled in the study.
• A hematocrit >54
• 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.
• Known hypersensitivity to Clomid
• Symptomatic cataracts (nuclear sclerosis cataract or cortical cataract grade > 2 based on 0-4 scale or any evidence of posterior subcapsular cataract)
• Abnormal fundoscopy exam such as central retinal vein occlusion
• 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
• Have received a diagnosis of irreversible infertility or compromised fertility (cryptorchism, Kallman Syndrome, primary hypogonadism, vasectomy, or tumors of the pituitary), or history of evaluation or treatment for low fertility
• Current or history of breast cancer
• Current or history of prostate cancer or a suspicion of prostate disease unless ruled out by prostate biopsy, or a PSA>3.6
• Presence or history of known hyperprolactinemia with or without a tumor (prolactin > 20 ng/mL).
• Chronic use of medications such as glucocorticoids (chronic use of inhaled or topical glucocorticoids is acceptable)
• History of drug abuse or chronic narcotic use including methadone
• A recent history of alcoholism or illegal substance or steroid abuse (<2 years) or presence of moderate alcohol use (>21 drinks per week)
• Subjects with known history of HIV and/or Hepatitis C
• Subjects with end stage renal disease
• History of liver disease (including malignancy) or a confirmed AST or ALT >3 times the upper limit of normal
• History of clinically relevant myocardial infarction (within the previous year), unstable angina, symptomatic heart failure, ventricular dysrhythmia or know history of QTc interval prolongation
• History of clinically relevant cerebrovascular disease
• History of venous thromboembolic disease (e.g. deep vein thrombosis or pulmonary embolism)
• History of erythrocytosis or polycythemia
• Subjects unable to provide a semen sample in a sponsor-approved clinic
• Enrollment in a previous Androxal study
• Subjects who have Type I Diabetes

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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120 participants in 3 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Androxal Placebo and Gel Placebo

Treatment:

Drug: Placebo Gel

Drug: Placebo Capsules

AndroGel Treatment

Active Comparator group

Description:

AndroGel 1.62% and Placebo Capsules

Treatment:

Drug: Placebo Capsules

Drug: AndroGel 1.62%

Androxal Treatment

Experimental group

Description:

Androxal 12.5 mg or 25mg and Placebo Gel

Treatment:

Drug: Androxal 12.5 mg or 25 mg

Drug: Placebo Gel