Hypogonadism
Conditions
Keywords
testosterone, male hypogonadism, low testosterone
Brief summary
The purpose of this pharmacokinetic study is to determine whether oral testosterone (T) ester formulations can be used effectively to treat men with low testosterone.
Detailed description
Determination of the steady-state serum T pharmacokinetic profiles for two oral formulations of T-esters \[testosterone undecanoate (TU) and TU combined with testosterone enanthate (TE)\] administered bis in die (BID) to 29 hypogonadal adult male subjects. TU was evaluated in total daily doses of 400 and 600 mg equivalents of T given twice daily for 7 or 8 days; TU + TE was evaluated in total daily doses of 600 and 800 mg equivalents of T given twice daily for 7 days. All subjects were enrolled into a single group and proceeded through the four Treatment Periods 1-4 in a sequential manner. In Treatment Period 3 the effect of food on the study-state pharmacokinetics profile of the TU formulation was evaluated.
Interventions
DRUGOral testosterone undecanoate (TU) (300 mg T equivalents/dose)
Three capsules each containing 100 mg testosterone (T) as TU, BID. 300 mg T equivalents BID 30 minutes after initiation of breakfast and dinner meals for 7 days. A 7-14 day washout period occurred between successive Treatment Periods.
DRUGOral testosterone undecanoate (TU) combined with testosterone enanthate (TE) (400 mg T equivalents/dose)
Two capsules each containing 100 mg T as TU and 100 mg T as TE, BID. 400 mg T equivalents BID 30 minutes after initiation of breakfast and dinner meals for 7 days. A 7-14 day washout period occurred between successive Treatment Periods.
DRUGOral testosterone undecanoate (TU) (200 mg T equivalents/dose with and without food)
Two capsules each containing 100 mg T as TU, BID for 8 days. 200 mg T equivalents BID 30 minutes after initiation of meals (breakfast and dinner), except for Day 8 when the morning dose was administered fasting. A 7-14 day washout period occurred between successive Treatment Periods.
DRUGOral testosterone undecanoate (TU) combined with testosterone enanthate (TE) (300 mg T equivalents/dose)
Two capsules each containing 150 mg T as TU and 150 mg T as TE, BID. 300 mg T equivalents BID 30 minutes after initiation of breakfast and dinner meals for 7 days.
Sponsors
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Clarus Therapeutics, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
All subjects were enrolled into a single group and proceeded through the four Treatment Periods 1-4 in a sequential manner.
Eligibility
Sex/Gender
MALE
Age
18 Years to 68 Years
Healthy volunteers
No
Inclusion criteria
* Male, ages 18-68 * Serum total T less than or equal to 275 ng/dL
Exclusion criteria
* Significant intercurrent disease of any type, in particular, liver, kidney or heart disease, uncontrolled diabetes mellitus or psychiatric illness. * Abnormal prostate digital rectal examination, elevated prostate-specific antigen (PSA), American Urological Association (AUA) symptom score of \>15, and/or history of prostate cancer. * Hematocrit of \<35 or \>50% * Body mass index (BMI) \>36 * Serum transaminases \> 2 times upper limit of normal or serum bilirubin \> 2.0 mg/dL
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum Testosterone Average Concentration (Cavg) (ng/dL) | 30 minutes pre-dose and 0, 1, 2, 4, 8, 12 hours and 0,1, 2, 4, 8, and 12 hours post respective AM/PM doses | Sampling to determine serum T Cavg post AM and PM doses and for 24 hours in Treatment Periods 1, 2, and 4. Sampling to determine serum T Cavg post AM dose with food (Day 7) and fasting (Day 8) in Treatment Period 3. |
| Serum Testosterone Area Under Curve (AUC) (0-24) (ng•hr/dL) | 30 minutes pre-dose and 0, 1, 2, 4, 8, 12 hours and 0,1, 2, 4, 8, and 12 hours post respective AM/PM doses | Sampling to determine serum T AUC post AM and PM doses and for 24 hours in Treatment Periods 1, 2, and 4. Sampling to determine serum T AUC with food (Day 7) and fasting (Day 8) in Treatment Period 3. |
Countries
United States
Participant flow
Recruitment details
A total of 45 subjects were screened at 4 study sites (1 university medical center and 3 clinical sites). 29 hypogonadal males met all eligibility requirements and were enrolled with first study drug administration on June 13, 2008.
Pre-assignment details
After signing an informed consent form, subjects underwent a screening evaluation up to 28 days prior to the first dose of study drug. 29 subjects meeting the admission criteria, began Treatment Period 1 intervention (7 days) followed by a 7-14 day washout period and then proceeded to Treatment Periods 2-4. A 7-14 day washout period occurred between successive Treatment Periods. Treatment Periods 1, 2, and 4 had intervention for 7 days and Treatment Period 3 had intervention for 8 days.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Repeat dose, sequential cross-over study including 4 treatment periods with a 7-14 day washout between successive periods:
Period 1: Three capsules each containing 100 mg testosterone (T) as testosterone undecanoate (TU), BID, 30 minutes after initiation of breakfast and dinner meals for 7 days.
Period 2: Two capsules each containing 200 mg T as TU and testosterone enanthate (TE), BID, 30 minutes after initiation of breakfast and dinner meals for 7 days.
Period 3: Two capsules each containing 100 mg T as TU, BID for 8 days except for Day 8 when the morning dose was administered fasting.
Period 4: Two capsules each containing 150 mg T as TU and TE, BID, 30 minutes after initiation of breakfast and dinner meals for 7 days. | 29 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Treatment Period 1 | Adverse Event | 1 |
| Treatment Period 1 | Withdrawal by Subject | 2 |
| Treatment Period 3 | Withdrawal by Subject | 1 |
| Treatment Period 4 | Adverse Event | 1 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 48.6 years STANDARD_DEVIATION 10.23 |
| Body Mass Index (BMI) (kg/m^2) | 30.4 kg/m^2 STANDARD_DEVIATION 3.43 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Height | 69.9 inches STANDARD_DEVIATION 4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 27 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 29 Participants |
| Total Testosterone (ng/dL) | 169.0 ng/dL STANDARD_DEVIATION 82.8 |
| Weight | 212.2 pounds STANDARD_DEVIATION 38.68 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 29 |
| other Total, other adverse events | 19 / 29 |
| serious Total, serious adverse events | 1 / 29 |
Outcome results
Primary
Serum Testosterone Area Under Curve (AUC) (0-24) (ng•hr/dL)
Sampling to determine serum T AUC post AM and PM doses and for 24 hours in Treatment Periods 1, 2, and 4. Sampling to determine serum T AUC with food (Day 7) and fasting (Day 8) in Treatment Period 3.
Time frame: 30 minutes pre-dose and 0, 1, 2, 4, 8, 12 hours and 0,1, 2, 4, 8, and 12 hours post respective AM/PM doses
Population: All available individual serum concentrations and pharmacokinetic parameter estimates were reported; missing data were not imputed. For 1 subject in Treatment Period 1 and 1 subject in Treatment Period 4 there were insufficient data to calculate all pharmacokinetic parameters.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Period 1 | Serum Testosterone Area Under Curve (AUC) (0-24) (ng•hr/dL) | AUC (12-24) (PM dose) with food | 9830 (ng•hr/dL) | Standard Deviation 3489 |
| Treatment Period 1 | Serum Testosterone Area Under Curve (AUC) (0-24) (ng•hr/dL) | AUC (0-24) | 19009 (ng•hr/dL) | Standard Deviation 6102 |
| Treatment Period 1 | Serum Testosterone Area Under Curve (AUC) (0-24) (ng•hr/dL) | AUC (0-12) (AM dose) with food | 9179 (ng•hr/dL) | Standard Deviation 3990 |
| Treatment Period 2 | Serum Testosterone Area Under Curve (AUC) (0-24) (ng•hr/dL) | AUC (12-24) (PM dose) with food | 7812 (ng•hr/dL) | Standard Deviation 2837 |
| Treatment Period 2 | Serum Testosterone Area Under Curve (AUC) (0-24) (ng•hr/dL) | AUC (0-12) (AM dose) with food | 7881 (ng•hr/dL) | Standard Deviation 3524 |
| Treatment Period 2 | Serum Testosterone Area Under Curve (AUC) (0-24) (ng•hr/dL) | AUC (0-24) | 15693 (ng•hr/dL) | Standard Deviation 5527 |
| Treatment Period 3 | Serum Testosterone Area Under Curve (AUC) (0-24) (ng•hr/dL) | AUC (0-12) (AM dose) fasting | 2894 (ng•hr/dL) | Standard Deviation 1267 |
| Treatment Period 3 | Serum Testosterone Area Under Curve (AUC) (0-24) (ng•hr/dL) | AUC (0-12) (AM dose) with food | 6217 (ng•hr/dL) | Standard Deviation 2792 |
| Treatment Period 4 | Serum Testosterone Area Under Curve (AUC) (0-24) (ng•hr/dL) | AUC (0-12) (AM dose) with food | 6601 (ng•hr/dL) | Standard Deviation 4614 |
| Treatment Period 4 | Serum Testosterone Area Under Curve (AUC) (0-24) (ng•hr/dL) | AUC (12-24) (PM dose) with food | 2894 (ng•hr/dL) | Standard Deviation 1267 |
| Treatment Period 4 | Serum Testosterone Area Under Curve (AUC) (0-24) (ng•hr/dL) | AUC (0-24) | 12980 (ng•hr/dL) | Standard Deviation 6926 |
Primary
Serum Testosterone Average Concentration (Cavg) (ng/dL)
Sampling to determine serum T Cavg post AM and PM doses and for 24 hours in Treatment Periods 1, 2, and 4. Sampling to determine serum T Cavg post AM dose with food (Day 7) and fasting (Day 8) in Treatment Period 3.
Time frame: 30 minutes pre-dose and 0, 1, 2, 4, 8, 12 hours and 0,1, 2, 4, 8, and 12 hours post respective AM/PM doses
Population: All available individual serum concentrations and pharmacokinetic parameter estimates were reported; missing data were not imputed. For 1 subject in Treatment Period 1 and 1 subject in Treatment Period 4 there were insufficient data to calculate all pharmacokinetic parameters.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Period 1 | Serum Testosterone Average Concentration (Cavg) (ng/dL) | Cavg (PM dose) with food | 819 ng/dL | Standard Deviation 291 |
| Treatment Period 1 | Serum Testosterone Average Concentration (Cavg) (ng/dL) | Cavg (0-24) | 792 ng/dL | Standard Deviation 254 |
| Treatment Period 1 | Serum Testosterone Average Concentration (Cavg) (ng/dL) | Cavg (AM dose) with food | 765 ng/dL | Standard Deviation 333 |
| Treatment Period 2 | Serum Testosterone Average Concentration (Cavg) (ng/dL) | Cavg (PM dose) with food | 651 ng/dL | Standard Deviation 236 |
| Treatment Period 2 | Serum Testosterone Average Concentration (Cavg) (ng/dL) | Cavg (AM dose) with food | 657 ng/dL | Standard Deviation 294 |
| Treatment Period 2 | Serum Testosterone Average Concentration (Cavg) (ng/dL) | Cavg (0-24) | 654 ng/dL | Standard Deviation 230 |
| Treatment Period 3 | Serum Testosterone Average Concentration (Cavg) (ng/dL) | Cavg (AM dose) fasting | 241 ng/dL | Standard Deviation 106 |
| Treatment Period 3 | Serum Testosterone Average Concentration (Cavg) (ng/dL) | Cavg (AM dose) with food | 518 ng/dL | Standard Deviation 233 |
| Treatment Period 4 | Serum Testosterone Average Concentration (Cavg) (ng/dL) | Cavg (AM dose) with food | 533 ng/dL | Standard Deviation 385 |
| Treatment Period 4 | Serum Testosterone Average Concentration (Cavg) (ng/dL) | Cavg (PM dose) with food | 548 ng/dL | Standard Deviation 250 |
| Treatment Period 4 | Serum Testosterone Average Concentration (Cavg) (ng/dL) | Cavg (0-24) | 541 ng/dL | Standard Deviation 289 |