Secondary Hypogonadism
Conditions
Brief summary
ZA-300 is meant to determine the safety profile of Androxal (enclomiphene citrate) in men with secondary hypogonadism.
Detailed description
This study is a phase III, open label safety study with a six month active dosing period. All subjects will be started at 12.5 mg Androxal and titrated to 25 mg if needed. Safety will be assessed by physical and visual acuity exams, slit lamp eye exams, clinical laboratory tests and adverse event reporting.
Interventions
DRUGAndroxal
Androxal, oral, 12.5 mg capsule, taken once daily. Dose may be increased from 12.5 mg to 25 mg if indicated
Sponsors
Repros Therapeutics Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Secondary hypogonadal males between the ages of 18 and 65 2. Men currently using topical testosterone products should wash-out for at least 7 days before Visit 1. 3. All clinical laboratory tests within normal ranges (any clinically significant deviation of laboratory results will require approval of sponsor) 4. Previously or concurrently diagnosed as having secondary hypogonadism and confirmed with morning testosterone level \< 350 ng/dL for men age \< 55 and \< 300ng/dl for men age 55-65 5. LH \< 15mIU/mL (at Visit 1 only) 6. Ability to complete the study in compliance with the protocol 7. Ability to understand and provide written informed consent.
Exclusion criteria
1. Use of an injectable pelleted testosterone within 6 months prior to study (men currently on topical testosterone products may be enrolled in the study after a 7-day washout period). 2. Use testosterone injection, spironolactone, cimetidine, Clomid, 5α-reductase inhibitors, hCG, androgen, estrogen, anabolic steroid, DHEA, or herbal hormone products during the study 3. Use of Clomid in the past year 4. Uncontrolled hypertension based on the Investigator's assessment at baseline. Subjects treated for Type II diabetes will be allowed into the study. 5. A hematocrit ≥ 51% or a hemoglobin ≥ 17 g/dL 6. Clinically significant abnormal findings on screening examination, based on the Investigator's assessment. 7. 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. 8. Known hypersensitivity to Clomid 9. Symptomatic cataracts (nuclear sclerosis cataract or cortical cataract grade \> 2 based on 0-4 scale or any trace of posterior subcapsular cataract) 10. 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 11. Irreversibly infertile or compromised fertility (cryptorchism, Kallman Syndrome, primary hypogonadism, or tumors of the pituitary) 12. Current or history of breast cancer 13. Current or history of prostate cancer or a suspicion of prostate disease unless ruled out by prostate biopsy, or a PSA \> 3.6 14. Presence or history of known hyperprolactinemia with or without a tumor 15. Chronic use of medications use such as glucocorticoids 16. Chronic use of narcotics 17. Subjects know to be positive for HIV 18. End stage renal disease 19. Subjects with cystic fibrosis (mutation of the CFTR gene) 20. Enrollment in a previous Androxal study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Total Morning Testosterone at 26 Weeks | 6 months | Changes in values from baseline of total morning testosterone levels at Week 26 |
| Change From Baseline in LH | 6 months | Mean change from baseline in LH at end of treatment (26 weeks) |
| Absolute Values of Morning Testosterone | 6 months | Absolute values of morning testosterone at end of treatment (26 weeks) |
| Mean Change From Baseline FPG | 6 months | Mean changes in Fasting Plasma Glucose from baseline to end of treatment (26 weeks) |
| Change From Baseline in BMI | 6 months | Mean change from baseline in BMI at end of treatment (26 weeks) |
| Change From Baseline in FSH | 6 months | Change from baseline in FSH at end of treatment (26 weeks) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Androxal 12.5 mg Androxal 12.5 mg daily
Androxal: Androxal, oral, 12.5 mg capsule, taken once daily. Dose may be increased from 12.5 mg to 25 mg if indicated | 216 |
| Androxal 25 mg Androxal 25 mg daily
Androxal: Androxal, oral, 12.5 mg capsule, taken once daily. Dose may be increased from 12.5 mg to 25 mg if indicated | 283 |
| Total | 499 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 15 | 8 |
| Overall Study | Eligibility error | 3 | 0 |
| Overall Study | Lab assessment | 2 | 1 |
| Overall Study | Lack of Efficacy | 0 | 3 |
| Overall Study | Lost to Follow-up | 19 | 14 |
| Overall Study | Needed prohibited meds | 1 | 0 |
| Overall Study | PCP decision | 1 | 0 |
| Overall Study | Physician Decision | 2 | 0 |
| Overall Study | Protocol Violation | 2 | 2 |
| Overall Study | Sponsor decision | 4 | 1 |
| Overall Study | Subject relocation | 2 | 0 |
| Overall Study | Withdrawal by Subject | 6 | 20 |
Baseline characteristics
| Characteristic | Androxal 12.5 mg | Androxal 25 mg | Total |
|---|---|---|---|
| Age, Continuous | 47.5 years STANDARD_DEVIATION 8.5 | 49.5 years STANDARD_DEVIATION 7.7 | 48.6 years STANDARD_DEVIATION 8.1 |
| Region of Enrollment United States | 216 participants | 283 participants | 499 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 216 Participants | 283 Participants | 499 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 66 / 207 | 92 / 283 |
| serious Total, serious adverse events | 6 / 207 | 9 / 283 |
Outcome results
Primary
Absolute Values of Morning Testosterone
Absolute values of morning testosterone at end of treatment (26 weeks)
Time frame: 6 months
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Androxal 12.5 mg | Absolute Values of Morning Testosterone | 511.6 ng/dL | Standard Deviation 140.8 |
| Androxal 25 mg | Absolute Values of Morning Testosterone | 416.7 ng/dL | Standard Deviation 154.7 |
Primary
Change From Baseline in BMI
Mean change from baseline in BMI at end of treatment (26 weeks)
Time frame: 6 months
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Androxal 12.5 mg | Change From Baseline in BMI | 0.2 kg/m2 | Standard Deviation 1.4 |
| Androxal 25 mg | Change From Baseline in BMI | 0.3 kg/m2 | Standard Deviation 1.1 |
Primary
Change From Baseline in FSH
Change from baseline in FSH at end of treatment (26 weeks)
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Androxal 12.5 mg | Change From Baseline in FSH | 5.20 U/L | Standard Deviation 5.19 |
| Androxal 25 mg | Change From Baseline in FSH | 5.42 U/L | Standard Deviation 5.48 |
Primary
Change From Baseline in LH
Mean change from baseline in LH at end of treatment (26 weeks)
Time frame: 6 months
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Androxal 12.5 mg | Change From Baseline in LH | 4.81 mIu/mL | Standard Deviation 5.69 |
| Androxal 25 mg | Change From Baseline in LH | 4.27 mIu/mL | Standard Deviation 4.29 |
Primary
Change From Baseline in Total Morning Testosterone at 26 Weeks
Changes in values from baseline of total morning testosterone levels at Week 26
Time frame: 6 months
Population: Intent to Treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Androxal 12.5 mg | Change From Baseline in Total Morning Testosterone at 26 Weeks | 280.9 ng/dL | Standard Deviation 141.4 |
| Androxal 25 mg | Change From Baseline in Total Morning Testosterone at 26 Weeks | 214.7 ng/dL | Standard Deviation 154.7 |
Primary
Mean Change From Baseline FPG
Mean changes in Fasting Plasma Glucose from baseline to end of treatment (26 weeks)
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Androxal 12.5 mg | Mean Change From Baseline FPG | -5.4 mg/dL | Standard Deviation 30.8 |
| Androxal 25 mg | Mean Change From Baseline FPG | -5.0 mg/dL | Standard Deviation 29.3 |