InfertilityPhase 2/3NCT02160704
Androxal in Male Infertility
A Phase 2/3 study testing Enclomiphene citrate in people with Infertility, run by Baylor College of Medicine at 1 site in United States.
Trial summary
This is an exploratory, single center, randomized, parallel, double-blind placebo- and active-controlled trial in adult males ages 18 to 35 years of age who have male infertility of unknown cause. Approximately 50 men will be randomly assigned to one of two treatment groups according to a 1:1 ratio. Read more about this study
- Who is it for?
- Ages 18 to 35 years, men only
- Conditions the study is for
- Infertility
- 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
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Sep 2014to 2 Aug 2016
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
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 35 years
- Men only
- No healthy volunteers
- Adult
Who may be able to join
- Men having idiopathic male infertility with sperm concentration <15million/ml (on 2 baseline semen analyses)
- Serum total testosterone < 300ng/dL if oligospermia (sperm concentration <15million/ml)
- Any testosterone if nonobstructive azoospermia (no sperm in the ejaculate)
- Men aged 18-35 living in stable relationship and desiring fertility
- Normal female partner evaluation as reported by the patient
- Ability to complete the study in compliance with the protocol
- Ability to understand and provide written informed consent
Who cannot join
- Men desiring operation for fertility (i.e. varicocelectomy) or couples desiring assisted reproductive technologies such as intrauterine insemination IUI, in vitro fertilization IVF and intracytoplasmic sperm injection ICSI) within study completion (5 months)
- Clinically significant medical condition rendering the subjects infertile including tumors of the pituitary, laboratory abnormalities
- Patients having received an investigational drug / clomiphene citrate, antioxidants, multi-vitamin in the past 30 days prior to study
- Previous treatment with androgens, estrogens, DHEA, testosterone or testosterone analogues in injectable, oral, topical or other forms for the treatment of AIHH who have not discontinued for at least 1 month prior to the start of the treatment phase
- Clinically significant abnormal findings on screening examination as determined by the investigator
- Known hypersensitivity to clomiphene citrate
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- Current or history of breast cancer
- Any condition which in the opinion of the investigator would interfere with the participant's ability to provide informed consent, comply with the study instructions, possibly confound interpretation of the study results, or endanger the participant if he took part in the study
- Have received a diagnosis of irreversible infertility or compromised fertility (cryptorchidism, Kallman Syndrome, vasectomy, or tumors of the pituitary)
- Current or history of prostate cancer or a suspicion of prostate disease
- Presence or history of known hyperprolactinemia (prolactin > 17ng/dl) with or without a tumor
- Chronic use of medications use such as glucocorticoids (chronic use of inhaled or topical glucocorticoids is acceptable)
- No current drug abuse or chronic narcotic use including methadone
- Subjects with known history of HIV and/or Hepatitis C
- Subjects with end stage renal disease
- Subjects with cystic fibrosis (mutation of the CFTR gene)
- 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 known 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 (HCt > 54)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: PHASE 2b RANDOMIZED, PARALLEL, DOUBLE-BLIND, PLACEBO-CONTROLLED EXPLORATORY STUDY TO EVALUATE THE EFFICACY OF ANDROXAL IN IDIOPATHIC MALE INFERTILITY (PROTOCOL #01-14-40-08)
This is an exploratory, single center, randomized, parallel, double-blind placebo- and active-controlled trial in adult males ages 18 to 35 years of age who have male infertility of unknown cause. Approximately 50 men will be randomly assigned to one of two treatment groups according to a 1:1 ratio. About half of the men will receive 25mg Androxal and half of the men will receive a placebo (non-active pill) for 16 weeks. This study will last approximately 4 months and involve up to 7 visits.
The purpose of this study is to determine the effect the Androxal on sperm production.
Read the detailed description
It has been estimated that 4 to 5 million men in the United States are testosterone deficient, but fewer than 10% currently receive testosterone replacement therapy. There are many reasons for the low number of men receiving testosterone replacement therapy, one of which is the route of administration. The currently approved androgen therapies are oral products, injectables, patches, buccal systems, and gels, and each has disadvantages. Oral preparations may be associated with hepatotoxicity and produce unfavorable effects on serum lipid profiles and carbohydrate metabolism. Injectables are associated with uneven levels of serum testosterone leading to fluctuations in mood, libido, and energy levels. Patches may require intrusive preparation, cause skin irritation or not adhere properly. A testosterone gel has overcome some of the above problems and has gained acceptance, but there are indications that men do not apply the gel correctly.
Previous studies showed that Androxal significantly increases total testosterone levels in men with low values at baseline. Additional studies found not only was Androxal non inferior to a topical gel, it was found to maintain sperm counts in the normal range.
Subjects will be randomized into one of the two treatment arms, using a block size of 4. The order in which the treatments are assigned in each block is randomized and this process is repeated for consecutive blocks of subjects until all subjects are randomized. This process ensures that after every fourth randomized subject, the number of subjects in each treatment group is equal.
To allow subjects in screening once the target 50 subjects have been enrolled and to account for dropouts, 75 randomization codes will be generated. As subjects are enrolled in the study, they will be assigned unique consecutive numbers starting at 001. At least 50 subjects who meet all the entry criteria will be randomized 1:1 such that approximately 25 subjects are assigned to the Androxal treatment arm and approximately 25 subjects are assigned to the placebo arm.
Placebo controlled studies are the gold standard of clinical trials and should be attempted whenever the indication and current medical practice will allow. This study is investigating a product to increase sperm concentration in subjects with idiopathic male infertility and secondary hypogonadism, low testosterone. Subjects with idiopathic male infertility do not require treatment to be healthy and approximately 18 weeks on a placebo is unlikely to harm the subjects in any way. Standard of care for idiopathic male infertility today allows subjects and physicians the option to not medically treat the disease. Therefore, the use of a placebo control in this study is well justified and will provide the best mechanism to assess treatment effect.
- Conditions
- Infertility
- Being tested
- Enclomiphene citrate, Placebo
- Keywords
- Sperm density, Testosterone, Hypogonadism
- Medical subject headings
- Infertility, 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
25 mg daily for 16 weeks
PlaceboOther
Also called sugar pill
placebo daily for 16 weeks
| Study group | Role | What they receive |
|---|---|---|
| Arm 1(IP) | Experimental | Enclomiphene citrate capsules 25 mg 1x daily for 16 weeks Receives: Drug: Enclomiphene citrate |
| Arm 2 (Placebo) | Placebo comparator | Placebo capsule 1x daily for 16 weeks Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Doubling of total motile sperm count
Measured: 16 weeks
Secondary outcomes (3)
Morning hormone levels
Assess changes in values from baseline of total morning testosterone, estrogen and dihydrotestosterone levels after 16 weeks of treatment with placebo or 25 mg Androxal
Measured: 16 weeks
Changes in questionnaire responses
Assess change from baseline to endpoint in Androgen Deficiency Aging Male (ADAM), International Prostate Symptom Score (I-PSS), Sexual health inventory in Male (SHIM) and psychosexual daily questionnaire (PDQ)
Measured: 16 weeks
BMI
Measured: 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2014 (estimated)
- Study start22 Sep 2014
- Primary completion2 Aug 2016
- Study completion2 Aug 2016
Why it stopped: Difficult eligibility and lack of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for InfertilityStudies of the same condition, open and under way.
- More trials run by Baylor College of MedicineThe sponsor's other registered studies.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Larry I. Lipshultz, Baylor College of Medicine
- Investigators
- Larry I. Lipshultz, MD, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02160704
- Sponsor's protocol ID
- H-33673
- Status last verified
- Jul 2019
- First submitted
- 5 Jun 2014
- Last updated
- 11 Jul 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PHASE 2b RANDOMIZED, PARALLEL, DOUBLE-BLIND, PLACEBO-CONTROLLED EXPLORATORY STUDY TO EVALUATE THE EFFICACY OF ANDROXAL IN IDIOPATHIC MALE INFERTILITY (PROTOCOL #01-14-40-08)
- ClinicalTrials.gov ID
- NCT02160704
- Acronym / sponsor ID
- H-33673
- Conditions
- Infertility
- Keywords
- Sperm density, Testosterone, Hypogonadism
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Difficult eligibility and lack of funding
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Study start
- 22 Sep 2014
- Primary completion
- 2 Aug 2016 (actual)
- Study completion
- 2 Aug 2016 (actual)
- First posted
- 11 Jun 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an exploratory, single center, randomized, parallel, double-blind placebo- and active-controlled trial in adult males ages 18 to 35 years of age who have male infertility of unknown cause. Approximately 50 men will be randomly assigned to one of two treatment groups according to a 1:1 ratio. About half of the men will receive 25mg Androxal and half of the men will receive a placebo (non-active pill) for 16 weeks. This study will last approximately 4 months and involve up to 7 visits.
The purpose of this study is to determine the effect the Androxal on sperm production.
Detailed description
It has been estimated that 4 to 5 million men in the United States are testosterone deficient, but fewer than 10% currently receive testosterone replacement therapy. There are many reasons for the low number of men receiving testosterone replacement therapy, one of which is the route of administration. The currently approved androgen therapies are oral products, injectables, patches, buccal systems, and gels, and each has disadvantages. Oral preparations may be associated with hepatotoxicity and produce unfavorable effects on serum lipid profiles and carbohydrate metabolism. Injectables are associated with uneven levels of serum testosterone leading to fluctuations in mood, libido, and energy levels. Patches may require intrusive preparation, cause skin irritation or not adhere properly. A testosterone gel has overcome some of the above problems and has gained acceptance, but there are indications that men do not apply the gel correctly.
Previous studies showed that Androxal significantly increases total testosterone levels in men with low values at baseline. Additional studies found not only was Androxal non inferior to a topical gel, it was found to maintain sperm counts in the normal range.
Subjects will be randomized into one of the two treatment arms, using a block size of 4. The order in which the treatments are assigned in each block is randomized and this process is repeated for consecutive blocks of subjects until all subjects are randomized. This process ensures that after every fourth randomized subject, the number of subjects in each treatment group is equal.
To allow subjects in screening once the target 50 subjects have been enrolled and to account for dropouts, 75 randomization codes will be generated. As subjects are enrolled in the study, they will be assigned unique consecutive numbers starting at 001. At least 50 subjects who meet all the entry criteria will be randomized 1:1 such that approximately 25 subjects are assigned to the Androxal treatment arm and approximately 25 subjects are assigned to the placebo arm.
Placebo controlled studies are the gold standard of clinical trials and should be attempted whenever the indication and current medical practice will allow. This study is investigating a product to increase sperm concentration in subjects with idiopathic male infertility and secondary hypogonadism, low testosterone. Subjects with idiopathic male infertility do not require treatment to be healthy and approximately 18 weeks on a placebo is unlikely to harm the subjects in any way. Standard of care for idiopathic male infertility today allows subjects and physicians the option to not medically treat the disease. Therefore, the use of a placebo control in this study is well justified and will provide the best mechanism to assess treatment effect.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1(IP) | Experimental | Drug: Enclomiphene citrateEnclomiphene citrate capsules 25 mg 1x daily for 16 weeks |
| Arm 2 (Placebo) | Placebo comparator | Other: PlaceboPlacebo capsule 1x daily for 16 weeks |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Men having idiopathic male infertility with sperm concentration <15million/ml (on 2 baseline semen analyses)
- Serum total testosterone < 300ng/dL if oligospermia (sperm concentration <15million/ml)
- Any testosterone if nonobstructive azoospermia (no sperm in the ejaculate)
- Men aged 18-35 living in stable relationship and desiring fertility
- Normal female partner evaluation as reported by the patient
Key exclusion criteria (21 listed)
- Men desiring operation for fertility (i.e. varicocelectomy) or couples desiring assisted reproductive technologies such as intrauterine insemination IUI, in vitro fertilization IVF and intracytoplasmic sperm injection ICSI) within study completion (5 months)
- Clinically significant medical condition rendering the subjects infertile including tumors of the pituitary, laboratory abnormalities
- Patients having received an investigational drug / clomiphene citrate, antioxidants, multi-vitamin in the past 30 days prior to study
- Previous treatment with androgens, estrogens, DHEA, testosterone or testosterone analogues in injectable, oral, topical or other forms for the treatment of AIHH who have not discontinued for at least 1 month prior to the start of the treatment phase
- Clinically significant abnormal findings on screening examination as determined by the investigator
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: Androxal25 mg daily for 16 weeks | Drug | Arm 1(IP) |
| PlaceboAlso: sugar pillplacebo daily for 16 weeks | Other | Arm 2 (Placebo) |
Primary outcome
Doubling of total motile sperm count
Time frame: 16 weeks
3 secondary outcomes
Morning hormone levels
Time frame: 16 weeks
Changes in questionnaire responses
Time frame: 16 weeks
BMI
Time frame: 16 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jul 2019.
- Individual participant dataSharing planned: No
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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.
Larry I. Lipshultz, MD principal investigator
Baylor College of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Enclomiphene citrate in people with Infertility, run by Baylor College of Medicine at 1 site 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 7 inclusion and 21 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: withdrawn, as of the sponsor's last update on 11 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Doubling of total motile sperm count (time frame: 16 weeks). 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 11 Jul 2019.