Secondary HypogonadismPhase 3NCT01739595
Phase III Study to Evaluate Morning Testosterone Normalization in Overweight Men With Secondary Hypogonadism
A Phase 3 study testing enclomiphene citrate in people with Secondary Hypogonadism, run by Repros Therapeutics Inc. at 13 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years, men only
- Conditions the study is for
- Secondary Hypogonadism
- What is being tested?
- enclomiphene citrate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 181 participants
- Where
- 13 sitesUnited States
- Study dates
- Nov 2012to Sep 2013
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- Men only
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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)
Show all 28Show fewer
- 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
- Chronic use of medications such as glucocorticoids
- 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 myocardial infarction, unstable angina, symptomatic heart failure, ventricular dysrhythmia or know history of QTc interval prolongation
- History of cerebrovascular disease
- History of venous thromboembolic disease (e.g. deep vein thrombosis or pulmonary embolism)
- History of erythrocytosis or polycythemia
- Subjects with cystic fibrosis (mutation of the CFTR gene)
- Subjects unable to provide a semen sample in a sponsor-approved clinic
- Enrollment in a previous Androxal study
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
United States13 sites
Meridien Research
Bradenton, Florida, 34208
All Medical Research
Cooper City, Florida, 33024
Clinical Research of South Florida
Coral Gables, Florida, 33134
Lone Peak Family Medicine
Draper, Utah, 84020
New Orleans Center for Clinical Research
Knoxville, Texas, 37920
Central Kentucky Research Associates
Lexington, Kentucky, 40509
Baptist Health Center for Clinical Research
Little Rock, Arkansas, 72205
Phase One Solutions
Miami Gardens, Florida, 33169
Coastal Clinical Research
Mobile, Alabama, 36608
Coastal Carolina Research Center
Mt. Pleasant, South Carolina, 29464
Rancho Cucamonga Clinical Trials
Rancho Cucamonga, California, 91730
Granger Medical Clinic
Riverton, Utah, 84065
Rochester Clinical Research
Rochester, New York, 14609
About this study
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
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.
Read the detailed description
Protocol ZA-302 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.
- Conditions
- Secondary Hypogonadism
- Being tested
- enclomiphene citrate, Placebo
- Medical subject headings
- Hypogonadism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
enclomiphene citrateDrug
Also called Androxal
oral, capsules, taken one time daily, for 3 months
PlaceboDrug
Also called Dummy
Oral capsule taken one time daily for 3 months
| Study group | Role | What they receive |
|---|---|---|
| Androxal 12.5 mg | Experimental | Androxal (enclomiphene citrate), 12.5 mg oral capsules taken once daily Receives: Drug: enclomiphene citrate |
| Androxal 25 mg | Experimental | Androxal (enclomiphene citrate), 25 mg oral capsules taken once daily Receives: Drug: enclomiphene citrate |
| Placebo | Placebo comparator | Placebo oral capsules taken one time daily Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2012 (estimated)
- Study startNov 2012
- Primary completionSep 2013
- Study completionSep 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Secondary HypogonadismStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 181 participants (actual)
Sponsor and investigators
- Lead sponsor
- Repros Therapeutics Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Joseph S Podolski, Study chair, Repros Therapeutics Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01739595
- Sponsor's protocol ID
- ZA-302
- Status last verified
- May 2015
- First submitted
- 29 Nov 2012
- Last updated
- 27 May 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01739595
- Acronym / sponsor ID
- ZA-302
- Conditions
- Secondary Hypogonadism
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 181 participants (actual)
- Lead sponsor
- Repros Therapeutics Inc.Industry (pharma, biotech, devices)
- Study start
- Nov 2012
- Primary completion
- Sep 2013 (actual)
- Study completion
- Sep 2013 (actual)
- First posted
- 3 Dec 2012 (estimated)
- Results
- Posted 27 May 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Protocol ZA-302 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Androxal 12.5 mg | Experimental | Drug: enclomiphene citrateAndroxal (enclomiphene citrate), 12.5 mg oral capsules taken once daily |
| Androxal 25 mg | Experimental | Drug: enclomiphene citrateAndroxal (enclomiphene citrate), 25 mg oral capsules taken once daily |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo oral capsules taken one time daily |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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)
Key exclusion criteria (28 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| enclomiphene citrateAlso: Androxaloral, capsules, taken one time daily, for 3 months | Drug | Androxal 12.5 mg, Androxal 25 mg |
| PlaceboAlso: DummyOral capsule taken one time daily for 3 months | Drug | Placebo |
Primary outcome
Subjects With Testosterone in Normal Range After Treatment
Time frame: 3 months
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.
Change in Sperm Concentration
Time frame: 3 months
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 May 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Sponsor home pageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joseph S Podolski study chair
Repros Therapeutics Inc.
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing enclomiphene citrate in people with Secondary Hypogonadism, run by Repros Therapeutics Inc. at 13 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 May 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Subjects With Testosterone in Normal Range After Treatment (time frame: 3 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 May 2015.