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Androxal in Male Infertility

Primary Purpose

Infertility

Status

Withdrawn

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Enclomiphene citrate

Placebo

About this trial

This is an interventional treatment trial for Infertility focused on measuring Sperm density, Testosterone, Hypogonadism

Eligibility Criteria

18 Years - 35 Years (Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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
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)

Sites / Locations

Baylor College of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm 1(IP)

Arm 2 (Placebo)

Arm Description

Enclomiphene citrate capsules 25 mg 1x daily for 16 weeks

Placebo capsule 1x daily for 16 weeks

Outcomes

Primary Outcome Measures

Doubling of total motile sperm count

Secondary Outcome Measures

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

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)

BMI

Full Information

NCT ID

NCT02160704

First Posted

June 5, 2014

Last Updated

July 10, 2019

Sponsor

Baylor College of Medicine

1. Study Identification

Unique Protocol Identification Number

NCT02160704

Brief Title

Androxal in Male Infertility

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)

Study Type

Interventional

2. Study Status

Record Verification Date

July 2019

Overall Recruitment Status

Withdrawn

Why Stopped

Difficult eligibility and lack of funding

Study Start Date

September 22, 2014 (undefined)

Primary Completion Date

August 2, 2016 (Actual)

Study Completion Date

August 2, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Baylor College of Medicine

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Infertility

Keywords

Sperm density, Testosterone, Hypogonadism

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm 1(IP)

Arm Type

Experimental

Arm Description

Enclomiphene citrate capsules 25 mg 1x daily for 16 weeks

Arm Title

Arm 2 (Placebo)

Arm Type

Placebo Comparator

Arm Description

Placebo capsule 1x daily for 16 weeks

Intervention Type

Drug

Intervention Name(s)

Enclomiphene citrate

Other Intervention Name(s)

Androxal

Intervention Description

25 mg daily for 16 weeks

Intervention Type

Other

Intervention Name(s)

Placebo

Other Intervention Name(s)

sugar pill

Intervention Description

placebo daily for 16 weeks

Primary Outcome Measure Information:

Title

Doubling of total motile sperm count

Time Frame

16 weeks

Secondary Outcome Measure Information:

Title

Morning hormone levels

Description

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

Time Frame

16 weeks

Title

Changes in questionnaire responses

Description

Time Frame

16 weeks

Title

BMI

Time Frame

16 weeks

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

35 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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 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)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Larry I. Lipshultz, MD

Organizational Affiliation

Baylor College of Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

Baylor College of Medicine

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

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