Healthy
Conditions
Keywords
Experimental, Acyline plus 27 oral testosterone pills, taken 3x/day
Brief summary
The purpose of this study is to test how the body absorbs a new form of oral testosterone (T). On Day 1 and Day 9 there are overnight stays in the General Clinical Research Center at the University of Washington to monitor blood testosterone levels over a 24-hour period.
Detailed description
We will administer two experimental drugs, acyline and oral testosterone. Acyline shots will be given on Day 0 to turn off the body's testosterone production for about 10-14 days. The next day, Day 1, subjects begin taking 300 mg modified slow-release testosterone pill by mouth, three times a day, around 9 AM, 1 PM, and 7 PM for a total of 27 pills. There are overnight stays on Day 1 and Day 9 to allow monitoring of blood testosterone levels over a 24 hour period, from @9 AM to 9 AM the next morning. At those visits, blood is drawn at baseline (before taking the pill) and at 1, 2, 4, 5, 6, 8, 10, 11, 12, 14, 16, and 24 hours after the morning dose. Acyline is an experimental drug. The FDA allows its use only in research with a small number of volunteers. We have used acyline in over 125 men without serious side effects. The use of testosterone in this study is experimental and there may be unknown or unanticipated risks.
Interventions
Oral Testosterone: 300 mg, pills, three times daily Day 1 - 10 (total of 27 pills)
DRUGAcyline
300 ug/kg injection on Day 0
Sponsors
GlaxoSmithKline
University of Washington
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* able and willing to * not participate in another drug study or donate blood, not take medications * use contraception, comply with the protocol
Exclusion criteria
* abnormal evaluation, based on physical exam, medical history, blood tests (including serum chemistry, hematology, HIV, HCV, hormone levels) * history or current use of alcohol, drug, steroid abuse, \>3 alcohol drinks/day * history of testicular disease, severe testicular trauma, major psychiatric disorder, bleeding disorders, current use of anti-coagulants or testosterone * participation in hormonal drug study within past month
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Testosterone Concentration | baseline & day 9 | initial pharmacokinetics \[PK\] (day 1) of oral testosterone dosed 3 times daily and the PK after 9 days of treatment |
| Mean Testosterone Concentration | baseline & day 9 | initial 24-hour pharmacokinetics (PK) of oral testosterone dosed 3 times daily and post 24-hour PK after 9 days of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Sex Hormone-Binding Globulin (SHGB)Concentration | baseline & day 9 | — |
| Mean SHGB Concentration | baseline & day 9 | — |
| Maximum Estradiol Concentration | baseline & day 9 | — |
| Maximum Dihydrotestosterone (DHT) Concentration | baseline & day 9 | — |
| Free T Maximum Concentration | baseline & day 9 | Free T normal range 4.7-18 ng/dL |
| Free Testosterone Mean Concentration | baseline & day 9 | Free T normal range 4.7-18 ng/dL |
| Mean Estradiol Concentration | baseline & day 9 | — |
| Mean Dihydrotestosterone (DHT) Concentration | baseline & day 9 | — |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited through news media (website)and college campus bulletin boards in Seattle, WA. between July-September 2010. All visits were at the University of Washington, Seattle, WA.
Pre-assignment details
14 subjects were screened and 2 did not meet inclusion criteria for untreated high blood pressure and peripheral arterial disease.
Participants by arm
| Arm | Count |
|---|---|
| Acyline and Oral Testosterone 300 mcg/kg acyline, and modified slow-release oral testosterone 300 mg | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | Acyline and Oral Testosterone |
|---|---|
| Age Continuous | 28.1 years |
| Body Mass Index (BMI) | 24.2 kg/m^2 STANDARD_DEVIATION 1.5 |
| Body Weight | 79.9 kg STANDARD_DEVIATION 7.5 |
| Follicle-stimulating hormone (FSH) | 3.2 IU/L STANDARD_DEVIATION 1.5 |
| Luteinizing hormone (LH) | 5.4 IU/L STANDARD_DEVIATION 4.4 |
| Prostate-specific antigen (PSA) | 0.91 ng/mL STANDARD_DEVIATION 0.56 |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 12 Participants |
| Testosterone | 510 ng/dL STANDARD_DEVIATION 13 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 8 / 12 |
| serious Total, serious adverse events | 0 / 12 |
Outcome results
Primary
Maximum Testosterone Concentration
initial pharmacokinetics \[PK\] (day 1) of oral testosterone dosed 3 times daily and the PK after 9 days of treatment
Time frame: baseline & day 9
Population: per protocol
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Acyline and 300 mg Oral Testosterone | Maximum Testosterone Concentration | Day 1 | 924 ng/dL | Geometric Coefficient of Variation 44 |
| Acyline and 300 mg Oral Testosterone | Maximum Testosterone Concentration | Day 9 | 741 ng/dL | Geometric Coefficient of Variation 71 |
p-value: 0.05t-test, 2 sided
Primary
Mean Testosterone Concentration
initial 24-hour pharmacokinetics (PK) of oral testosterone dosed 3 times daily and post 24-hour PK after 9 days of treatment
Time frame: baseline & day 9
Population: per protocol
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Acyline and 300 mg Oral Testosterone | Mean Testosterone Concentration | Day 1 | 378 ng/dL | Geometric Coefficient of Variation 45 |
| Acyline and 300 mg Oral Testosterone | Mean Testosterone Concentration | Day 9 | 315 ng/dL | Geometric Coefficient of Variation 41 |
Secondary
Free Testosterone Mean Concentration
Free T normal range 4.7-18 ng/dL
Time frame: baseline & day 9
Population: per protocol
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Acyline and 300 mg Oral Testosterone | Free Testosterone Mean Concentration | Day 1-2 | 8.7 ng/dL | Geometric Coefficient of Variation 43 |
| Acyline and 300 mg Oral Testosterone | Free Testosterone Mean Concentration | Day 9-10 | 8.3 ng/dL | Geometric Coefficient of Variation 37 |
Secondary
Free T Maximum Concentration
Free T normal range 4.7-18 ng/dL
Time frame: baseline & day 9
Population: per protocol
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Acyline and 300 mg Oral Testosterone | Free T Maximum Concentration | Day 1-2 | 24 ng/dL | Geometric Coefficient of Variation 47 |
| Acyline and 300 mg Oral Testosterone | Free T Maximum Concentration | Day 9-10 | 21 ng/dL | Geometric Coefficient of Variation 86 |
Secondary
Maximum Dihydrotestosterone (DHT) Concentration
Time frame: baseline & day 9
Population: per protocol
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Acyline and 300 mg Oral Testosterone | Maximum Dihydrotestosterone (DHT) Concentration | Day 1 | 233 ng/dL | Geometric Coefficient of Variation 49 |
| Acyline and 300 mg Oral Testosterone | Maximum Dihydrotestosterone (DHT) Concentration | Day 9 | 142 ng/dL | Geometric Coefficient of Variation 55 |
Secondary
Maximum Estradiol Concentration
Time frame: baseline & day 9
Population: per protocol
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Acyline and 300 mg Oral Testosterone | Maximum Estradiol Concentration | Day 1 | 14 ng/dL | Geometric Coefficient of Variation 28 |
| Acyline and 300 mg Oral Testosterone | Maximum Estradiol Concentration | Day 9 | 9 ng/dL | Geometric Coefficient of Variation 27 |
Secondary
Maximum Sex Hormone-Binding Globulin (SHGB)Concentration
Time frame: baseline & day 9
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Acyline and 300 mg Oral Testosterone | Maximum Sex Hormone-Binding Globulin (SHGB)Concentration | Day 1 | 31 ng/dL | Geometric Coefficient of Variation 48 |
| Acyline and 300 mg Oral Testosterone | Maximum Sex Hormone-Binding Globulin (SHGB)Concentration | Day 9 | 22 ng/dL | Geometric Coefficient of Variation 48 |
Secondary
Mean Dihydrotestosterone (DHT) Concentration
Time frame: baseline & day 9
Population: per protocol
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Acyline and 300 mg Oral Testosterone | Mean Dihydrotestosterone (DHT) Concentration | Day 1 | 96 ng/dL | Geometric Coefficient of Variation 38 |
| Acyline and 300 mg Oral Testosterone | Mean Dihydrotestosterone (DHT) Concentration | Day 9 | 69 ng/dL | Geometric Coefficient of Variation 41 |
Secondary
Mean Estradiol Concentration
Time frame: baseline & day 9
Population: per protocol
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Acyline and 300 mg Oral Testosterone | Mean Estradiol Concentration | Day 1 | 11 ng/dL | Geometric Coefficient of Variation 18 |
| Acyline and 300 mg Oral Testosterone | Mean Estradiol Concentration | Day 9 | 7 ng/dL | Geometric Coefficient of Variation 18 |
Secondary
Mean SHGB Concentration
Time frame: baseline & day 9
Population: per protocol
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Acyline and 300 mg Oral Testosterone | Mean SHGB Concentration | Day 1 | 27 ng/dL | Geometric Coefficient of Variation 46 |
| Acyline and 300 mg Oral Testosterone | Mean SHGB Concentration | Day 9 | 19 ng/dL | Geometric Coefficient of Variation 14 |