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%

• ClinicalTrials.gov Identifier: NCT01993212
• Recruitment Status: Completed
• First Posted: November 25, 2013
• Last Update Posted: October 1, 2014
• Sponsor: Repros Therapeutics Inc.
• Information provided by (Responsible Party): Repros Therapeutics Inc.

Study Description

Brief Summary:

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%.

Condition or disease	Intervention/treatment	Phase
Secondary Hypogonadism	Drug: Androxal 12.5 mg or 25 mg; Drug: AndroGel 1.62%; Drug: Placebo Capsules; Drug: Placebo Gel	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Study Start Date: January 2014
• Actual Primary Completion Date: September 2014
• Actual Study Completion Date: September 2014

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo; Androxal Placebo and Gel Placebo	Drug: Placebo Capsules; Drug: Placebo Gel
Active Comparator: AndroGel Treatment; AndroGel 1.62% and Placebo Capsules	Drug: AndroGel 1.62%; Drug: Placebo Capsules
Experimental: Androxal Treatment; Androxal 12.5 mg or 25mg and Placebo Gel	Drug: Androxal 12.5 mg or 25 mg; Drug: Placebo Gel

Outcome Measures

Primary Outcome Measures :

1. Comparison of the proportion of subjects meeting the composite endpoint for normal morning testosterone and semen concentration. [ Time Frame: 16 weeks of treatment ]
   Comparison of the proportion of subjects whose morning testosterone levels are within the normal range [300-1,040 ng/dL] and whose sperm concentration is 15 million/mL or greater following 16 weeks of treatment with Androxal, placebo or AndroGel 1.62%.

Secondary Outcome Measures :

1. Proportion of subjects with mean sperm concentration less than 15 million/mL after 16 weeks of treatment comparing Androxal to placebo in a non-inferiority assessment [ Time Frame: 16 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Florida

Jacksonville, Florida, United States

United States, New York

Albany, New York, United States

United States, North Carolina

Raleigh, North Carolina, United States

United States, Ohio

Cleveland, Ohio, United States

United States, Oregon

Medford, Oregon, United States

United States, Rhode Island

Warwick, Rhode Island, United States

United States, Texas

Houston, Texas, United States

Webster, Texas, United States

Sponsors and Collaborators

Repros Therapeutics Inc.

More Information

• Responsible Party: Repros Therapeutics Inc.
• ClinicalTrials.gov Identifier: NCT01993212
• Other Study ID Numbers: ZA-304
• First Posted: November 25, 2013
• Last Update Posted: October 1, 2014
• Last Verified: September 2014

Keywords provided by Repros Therapeutics Inc.:

Low Testosterone

Additional relevant MeSH terms:

Hypogonadism; Gonadal Disorders; Endocrine System Diseases; Enclomiphene; Testosterone; Androgens; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Estrogen Antagonists; Hormone Antagonists; Fertility Agents, Female; Fertility Agents; Reproductive Control Agents; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators