Healthy Males, Male Contraceptive
Conditions
Keywords
5α-reductase, androgen, dihydrotestosterone (DHT), drug delivery, oestradiol
Brief summary
The purpose of this study is to test how the body absorbs and processes new forms of oral testosterone. Information gained during the study may help develop better forms of testosterone therapy in the future.
Detailed description
We will be using three drugs: The first, acyline, temporarily turns off the body's production of testosterone for about two weeks. Subjects will receive acyline as shots three times over a six-week drug administration period. During the time when the body's production of testosterone is turned off, we will give testosterone either by itself or with a medication called finasteride by mouth twice daily for one week to see how much is absorbed and present in the bloodstream after administration. Subjects will go through three one-week study drug exposure periods. During two of the three one-week study drug administration periods subjects will also take a second medication, finasteride, by mouth twice daily. On the last day of each one-week drug administration period, subjects will be admitted to the University of Washington General Clinical Research Center overnight for monitoring of your blood testosterone levels. There will be 3 overnight visits for this study. This study will allow us to determine the absorption of testosterone taken by mouth, and the relative impact of two different doses of oral finasteride on testosterone absorption.
Interventions
DRUGFirst Intervention (7 days)
Acyline 300mcg/kg subcutaneous (days 1, 15 & 29) + testosterone undecanoate 200 mg, twice daily orally + finasteride placebo
OTHERFirst Washout (7 days)
Washout of 7 days between each of the 3 treatment arms
DRUGSecond Intervention (7 days)
Acyline 300mcg/kg subcutaneous + testosterone undecanoate 200 mg, twice daily orally + finasteride 0.5mg twice daily, orally
DRUGThird Intervention (7 days)
Acyline 300mcg/kg subcutaneous + testosterone undecanoate 200 mg, twice daily orally + finasteride 1mg twice daily, orally
OTHERSecond wash-out period
Washout of 7 days between each of the 3 treatment arms
Sponsors
National Institutes of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
University of Washington
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Males between 18 and 50 years of age * In good health based on normal screening evaluation (consisting of a medical history, physical exam normal serum chemistry, hematology, and baseline hormone levels. * Must agree to not participate in another research drug study * Must agree to not donate blood * Must be willing to comply with the study protocol and procedures
Exclusion criteria
* Men in poor general health, with abnormal blood results (clinical laboratory tests or hormone values) * A known history of alcohol or drug abuse * Participation in a long-term male contraceptive study within the past month * History of bleeding disorders or current use of anti-coagulants * History of sleep apnea * History of major psychiatric disorder * Body mass index \> 37 * Infertility * Hematocrit \> 55 or \< 30 * PSA \>4
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Testosterone Concentration | 0,1,2,4,8,and 12-hour post dose | Area under the curve of serum testosterone Pharmacokinetic measures time-weighted mean concentration calculated as area under the concentration curve (AUC) divided by time from initiation of dosing for the morning dose and corrected for differences in baseline hormone concentration. |
| Serum Dihydrotestosterone Concentration | 0,1,2,4,8,and 12-hour post dose | Area under the curve of serum dihydrotestosterone |
| Serum Estradiol Concentration | 0,1,2,4,8,and 12-hour post dose | Area under the curve of serum estradiol |
Countries
United States
Participant flow
Recruitment details
Men age 18-52 in good health were recruited through local newspapers and college campus flyers.
Pre-assignment details
12 subjects were screened; 11 enrolled (1 did not meet inclusion criteria-abnormal liver function test at baseline and excessive alcohol use). Each subject was administered each of the three treatments over a 6-week period with 1 week of no treatment (wash-out) between each of the treatment period.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants | 11 |
| Total | 11 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 32 years STANDARD_DEVIATION 9 |
| Body Mass Index (BMI) | 24 kg/m2 STANDARD_DEVIATION 3 |
| Height | 181 cm STANDARD_DEVIATION 7 |
| Serum dihydrotestosterone concentration | 32 ng/dL STANDARD_DEVIATION 12 |
| Serum oestradiol concentration | 15 pg/mL STANDARD_DEVIATION 5 |
| Serum testosterone concentration | 405 ng/dL STANDARD_DEVIATION 14 |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 11 Participants |
| Weight | 80 kg STANDARD_DEVIATION 13 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 11 | 2 / 11 | 3 / 11 |
| serious Total, serious adverse events | 0 / 11 | 0 / 11 | 0 / 11 |
Outcome results
Primary
Maximum Testosterone Concentration
Area under the curve of serum testosterone Pharmacokinetic measures time-weighted mean concentration calculated as area under the concentration curve (AUC) divided by time from initiation of dosing for the morning dose and corrected for differences in baseline hormone concentration.
Time frame: 0,1,2,4,8,and 12-hour post dose
Population: All participant received all treatments and is, therefore, included in the analysis population for all groups.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Acyline +Testosterone Undecanoate + Placebo | Maximum Testosterone Concentration | 471 ng*hr/dL |
| Acyline +Testosterone Undecanoate + 0.5mg Finasteride | Maximum Testosterone Concentration | 444 ng*hr/dL |
| Acyline +Testosterone Undecanoate + 1mg Finasteride | Maximum Testosterone Concentration | 543 ng*hr/dL |
Primary
Serum Dihydrotestosterone Concentration
Area under the curve of serum dihydrotestosterone
Time frame: 0,1,2,4,8,and 12-hour post dose
Population: All participants received all treatment, and is therefore, included in the analysis population for all three treatment groups.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Acyline +Testosterone Undecanoate + Placebo | Serum Dihydrotestosterone Concentration | 154 ng*hr/dL |
| Acyline +Testosterone Undecanoate + 0.5mg Finasteride | Serum Dihydrotestosterone Concentration | 118 ng*hr/dL |
| Acyline +Testosterone Undecanoate + 1mg Finasteride | Serum Dihydrotestosterone Concentration | 125 ng*hr/dL |
Primary
Serum Estradiol Concentration
Area under the curve of serum estradiol
Time frame: 0,1,2,4,8,and 12-hour post dose
Population: All participants received all treatment, and is therefore, included in the analysis population for all three treatment groups.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Acyline +Testosterone Undecanoate + Placebo | Serum Estradiol Concentration | 7.9 ng*hr/dL |
| Acyline +Testosterone Undecanoate + 0.5mg Finasteride | Serum Estradiol Concentration | 6.5 ng*hr/dL |
| Acyline +Testosterone Undecanoate + 1mg Finasteride | Serum Estradiol Concentration | 7.2 ng*hr/dL |