Secondary Hypogonadism
Conditions
Brief summary
The Purpose of the study is to determine the effects of Androxal on morning testosterone and reproductive status in men with secondary hypogonadism(confirmed morning Testosterone less than 250 ng/dL), compared to changes with placebo, or Testim (topical testosterone). The effects of Testim versus placebo on reproductive status will also be examined. Study subjects must not be currently using a topical testosterone.
Detailed description
This study is a phase IIb, 4 arm study with three month active dosing period. Three of the four treatment groups will be randomized to either Androxal or placebo in a double-blind fashion, and the fourth treatment group will receive open-label Testim. The doses of Androxal in the blinded portion of the study will be 12.5 mg and 25 mg, in capsule form.
Interventions
DRUGPlacebo
Placebo capsule 1x daily for 3 months
testosterone gel applied 1x daily for 3 months
DRUGAndroxal
Capsule of either 12.5 mg or 25 mg Androxal, 1x daily for 3 months
Sponsors
Repros Therapeutics Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
21 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Healthy males between the ages of 21 and 65 years of age * 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 and confirmed morning testosterone \<250ng/dL (two assessments at least 10 days apart) * Ability to complete the study in compliance with the protocol * Ability to understand and provide written informed consent * Agreement to use double barrier contraception if with a fertile female partner * Agreement to provide a semen sample in the clinic
Exclusion criteria
* Use of an injectable, oral, topical, or subcutaneous pelleted testosterone within 6 months prior to study * 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 but exhibiting glycemic control will be allowed into the study * A hematocrit \>50% or a hemoglobin \>17 g/dL * Clinically significant abnormal findings on screening examination * 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) * 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 hyperprolactinemia with or without a tumor * Chronic use of medications use such as glucocorticoids * Subjects with cystic fibrosis (mutation of the CFTR gene) * Subjects unable to provide a semen sample in the clinic * Subject has a BMI \>36 kg/m2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Total Morning Testosterone | 3 months | Changes in values from baseline in total morning testosterone levels at month 3 comparing Androxal 12.5 and 25 mg to placebo and Testim |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Luteinizing Hormone Levels | 3 months | Changes in values from baseline in LH at month 3 |
| Change in FSH After 3 Months of Treatment | 3 months | — |
| Reproductive Safety | 3 months | Change from baseline in sperm concentration |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo
Placebo: Placebo capsule 1x daily for 3 months | 28 |
| Testim (Topical Testosterone) Testim (topical testosterone)
topical testosterone: testosterone gel applied 1x daily for 3 months | 33 |
| Androxal 12.5 mg Androxal 12.5 mg/day
Androxal: Capsule of either 12.5 mg or 25 mg Androxal, 1x daily for 3 months | 27 |
| Androxal 25 mg Androxal 25 mg/day
Androxal: Capsule of either 12.5 mg or 25 mg Androxal, 1x daily for 3 months | 33 |
| Total | 121 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 | 3 |
| Overall Study | Did not qualify | 6 | 3 | 4 | 5 |
| Overall Study | Enrolled in error | 0 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 3 | 1 | 4 | 2 |
| Overall Study | Physician Decision | 0 | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 1 | 5 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 2 | 3 | 3 |
Baseline characteristics
| Characteristic | Total | Placebo | Testim (Topical Testosterone) | Androxal 12.5 mg | Androxal 25 mg |
|---|---|---|---|---|---|
| Age, Continuous | 50.6 years STANDARD_DEVIATION 11.2 | 51.6 years STANDARD_DEVIATION 11.7 | 52.0 years STANDARD_DEVIATION 10.6 | 49.7 years STANDARD_DEVIATION 11.6 | 49.2 years STANDARD_DEVIATION 10.9 |
| BMI | 32.1 kg/m2 STANDARD_DEVIATION 5.1 | 30.9 kg/m2 STANDARD_DEVIATION 4.2 | 33.1 kg/m2 STANDARD_DEVIATION 5.9 | 32.6 kg/m2 STANDARD_DEVIATION 5.2 | 31.7 kg/m2 STANDARD_DEVIATION 4.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 18 Participants | 4 Participants | 6 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 22 Participants | 7 Participants | 4 Participants | 5 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 78 Participants | 17 Participants | 23 Participants | 18 Participants | 20 Participants |
| Region of Enrollment United States | 121 participants | 28 participants | 33 participants | 27 participants | 33 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 121 Participants | 28 Participants | 33 Participants | 27 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 28 | 15 / 33 | 3 / 27 | 3 / 33 |
| serious Total, serious adverse events | 0 / 28 | 1 / 33 | 0 / 27 | 0 / 33 |
Outcome results
Primary
Change in Total Morning Testosterone
Changes in values from baseline in total morning testosterone levels at month 3 comparing Androxal 12.5 and 25 mg to placebo and Testim
Time frame: 3 months
Population: Intent to treat subjects with an assessment after baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Total Morning Testosterone | -16.9 ng/dL | Standard Deviation 47.5 |
| Testim (Topical Testosterone) | Change in Total Morning Testosterone | 253.7 ng/dL | Standard Deviation 292.3 |
| Androxal 12.5 mg | Change in Total Morning Testosterone | 258.5 ng/dL | Standard Deviation 201.5 |
| Androxal 25 mg | Change in Total Morning Testosterone | 197.3 ng/dL | Standard Deviation 162.6 |
Secondary
Change in FSH After 3 Months of Treatment
Time frame: 3 months
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in FSH After 3 Months of Treatment | -0.2 mIU/mL | Standard Deviation 0.7 |
| Testim (Topical Testosterone) | Change in FSH After 3 Months of Treatment | -4.4 mIU/mL | Standard Deviation 2.9 |
| Androxal 12.5 mg | Change in FSH After 3 Months of Treatment | 5.1 mIU/mL | Standard Deviation 6.2 |
| Androxal 25 mg | Change in FSH After 3 Months of Treatment | 7.4 mIU/mL | Standard Deviation 6.5 |
Secondary
Change in Luteinizing Hormone Levels
Changes in values from baseline in LH at month 3
Time frame: 3 months
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Luteinizing Hormone Levels | -0.1 mIU/mL | Standard Deviation 1 |
| Testim (Topical Testosterone) | Change in Luteinizing Hormone Levels | -2.4 mIU/mL | Standard Deviation 2.4 |
| Androxal 12.5 mg | Change in Luteinizing Hormone Levels | 4.8 mIU/mL | Standard Deviation 4.7 |
| Androxal 25 mg | Change in Luteinizing Hormone Levels | 6.9 mIU/mL | Standard Deviation 7.7 |
Secondary
Reproductive Safety
Change from baseline in sperm concentration
Time frame: 3 months
Population: Subjects with end of study assessments
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Reproductive Safety | -19.1 millions/mL | Standard Deviation 93.4 |
| Testim (Topical Testosterone) | Reproductive Safety | -29.5 millions/mL | Standard Deviation 39 |
| Androxal 12.5 mg | Reproductive Safety | 8.2 millions/mL | Standard Deviation 233.1 |
| Androxal 25 mg | Reproductive Safety | -2.8 millions/mL | Standard Deviation 167 |