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

NCT01739595 | Completed Phase 3 Results

• 1 other identifier: ZA-302
• Study Type: interventional
• Target: 181
• Locations: 1 country
• Sites: 13

Brief Summary

The purpose of ZA-302 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.

Conditions

Secondary Hypogonadism

Outcome Measures

Primary Outcomes (2)

• Subjects With Testosterone in Normal Range After Treatment

  Proportion (percent) of subjects with average serum concentration (Cavg) for T in the normal range (300 - 1040 ng/dL) after 12 weeks of treatment. Cavg was 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 coprimary endpoint based on the Cavg for testosterone would have 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

• Change in Sperm Concentration

  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

Study Arms (3)

Androxal 12.5 mg

EXPERIMENTAL

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

Drug: enclomiphene citrate

Androxal 25 mg

EXPERIMENTAL

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

Drug: enclomiphene citrate

Placebo

PLACEBO COMPARATOR

Placebo oral capsules taken one time daily

Drug: Placebo

Interventions

enclomiphene citrate DRUG

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

Also known as: Androxal

Androxal 12.5 mg; Androxal 25 mg

Placebo DRUG

Oral capsule taken one time daily for 3 months

Also known as: Dummy

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Overweight (BMI 25 to 42 kg/m2 inclusive) males age 18 to 60 inclusive
• All clinical laboratory tests within normal ranges (any clinically significant deviation of laboratory results will require approval of sponsor)
• 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.
• LH \< 9.4 mIU/mL (at Visit 1 only)
• Sperm count ≥ 15 million per milliliter (assessed twice 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 up to 6 semen sample in a sponsor-approved clinic on up to 6 separate occasions.

You may not qualify if:

• Any prior use of testosterone treatments 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
• 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.
• Clinically significant abnormal findings at Screening (Visit 1) or Baseline, based on the Investigator's assessment
• 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)
• 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 trace 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
• Irreversibly infertile or compromised fertility (cryptorchism, Kallman Syndrome, primary hypogonadism, vasectomy, or tumors of the pituitary)
• 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

Sponsors & Collaborators

• Repros Therapeutics Inc.: lead

Study Sites (13)

Coastal Clinical Research

Mobile, Alabama, 36608, United States

Location

Baptist Health Center for Clinical Research

Little Rock, Arkansas, 72205, United States

Location

Rancho Cucamonga Clinical Trials

Rancho Cucamonga, California, 91730, United States

Location

Meridien Research

Bradenton, Florida, 34208, United States

Location

All Medical Research

Cooper City, Florida, 33024, United States

Location

Clinical Research of South Florida

Coral Gables, Florida, 33134, United States

Location

Phase One Solutions

Miami Gardens, Florida, 33169, United States

Location

Central Kentucky Research Associates

Lexington, Kentucky, 40509, United States

Location

Rochester Clinical Research

Rochester, New York, 14609, United States

Location

Coastal Carolina Research Center

Mt. Pleasant, South Carolina, 29464, United States

Location

New Orleans Center for Clinical Research

Knoxville, Texas, 37920, United States

Location

Lone Peak Family Medicine

Draper, Utah, 84020, United States

Location

Granger Medical Clinic

Riverton, Utah, 84065, United States

Location

Related Links

• Sponsor home page

MeSH Terms

Conditions

Hypogonadism

Interventions

Enclomiphene

Condition Hierarchy (Ancestors)

Gonadal Disorders; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Clomiphene; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Jennifer Wike
• Organization: Repros Therapeutics Inc

jwike@reprosrx.com

2817193402

Study Officials

• Joseph S Podolski

  Repros Therapeutics Inc.

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2012
• First Posted: December 3, 2012
• Study Start: November 1, 2012
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2013
• Last Updated: May 27, 2015
• Results First Posted: May 27, 2015

Record last verified: 2015-05

Locations

US (13)