Hypogonadism
Conditions
Keywords
testosterone, male hypogonadism, low testosterone
Brief summary
Determine the serum pharmacokinetic profile for two oral formulations of T-esters (one TE and one TU) administered once -(QD) and twice-daily (BID) to hypogonadal men.
Detailed description
Five period cross-over study in which subjects received a single day of dosing in each period. Dosing was either QD or BID with one of two T esters (T-enanthate (TE) or T-undecanoate (TU)). Dosing was within 5 minutes of meals (breakfast and for BID dosing dinner). There was a minimum of a 5-day washout between periods. Subjects were hypogonadal men.
Interventions
DRUGTestosterone undecanoate
Single-day dose as QD or BID for 3 of 5 crossover periods
DRUGTestosterone enanthate
Single-day dose for 2 of 5 crossover periods
Sponsors
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Clarus Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Male, ages 18 to 65 Serum total testosterone less than or equal to 250 ng/dL Naive to androgen replacement therapy Subject must be on stable doses of thyroid or adrenal replacement hormones for at least 14 days prior to enrollment
Exclusion criteria
Significant intercurrent disease of any type, in particular, liver, kidney or heart disease, uncontrolled diabetes mellitus or psychiatric illness. Patients with treated hyperlipidemia will not be excluded provided they have been stable on their lipid-lowering mediation for at least three months. For non-insulin dependent diabetic subjects, HbA1c\>9%. Abnormal prostate digital rectal examination, elevated PSA (serum PSA \>4ng/mL), AUA Sympton Score greater than or equal to 15 points, and a history or prostate cancer. Serum transaminases \>2X upper limit of normal (ULN) or serum bilirubin \>2.0 mg/dL. History of severe or multiple allergies, severe adverse drug reaction or leucopenia. Known hypersensitivity to lidocaine or all surgical dressings. History of abnormal bleeding tendencies. Oral, topical, or buccal T therapy within the previous week, or intramuscular T injection within the previous 4 week. Use of dietary supplements that may increase serum T, such as androstenedione or DHEA, within the previous 4 weeks. Know malabsorption syndrome and/or current treatment with oral lipase inhibitors, bile acid-binding resins, colestipol, fibric acid derivatives, gemfibrozil, and probucol. Smokers who are unable to refrain from smoking during confinement periods. History of, or current evidence of, abuse of alcohol or any drug substance. Poor compliers or those unlikely to attend. Receipt of any drug as part of a research study within 30 days of inital dose administration in this study. Blood donation (usually 550 mL) within the 12-week period before the initial study dose. Hematocrit less than 35%. Known clinical polycythemia or hematocrit greater than 50%. Current use of paroxetine and clomipramine, antiandrogens, estrogens, p450 enzyme inducers, or barbiturates. History of sleep apnea.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Serum Testosterone Cavg | Concentrations at -0.5, 0, 1, 2, 4, 8, 12, 13, 14, 16, 20, 24 and 34 hours post dose | The objective of the study was to determine the single day serum pharmacokinetic profile for two oral formulations of T-esters (one TE and one TU formulation) administered once- and twice-daily to hypogonadal men. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Serum Dihydrotestosterone Cmax | 24 hours post-dose in each period | The objective of the study was to determine the single day serum pharmacokinetic profile for two oral formulations of T-esters (one TE and one TU formulation) administered once- and twice-daily to hypogonadal men. |
Countries
United States
Participant flow
Recruitment details
Cross over study with 5 periods. Twelve subjects enrolled and completed 5 crossover periods each.
Participants by arm
| Arm | Count |
|---|---|
| Testosterone Enanthate and Testosterone Undecanoate Period 1 - 400 mg T (as TE) QD Period 5 - 800 mg T (as TE) BID (400 mg/dose) Testosterone enanthate: Single-day dose for 2 of 5 crossover periods
Period 2 - 200 mg T (as TU) QD Period 3 - 200 mg T (as TU) BID (100 mg/dose) Period 4 - 400 mg T (as TU) BID (200 mg/dose) Testosterone undecanoate: Single-day dose as QD or BID for 3 of 5 crossover periods | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | Testosterone Enanthate and Testosterone Undecanoate |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants |
| Age, Continuous | 53 years |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 3 / 12 | 3 / 12 | 3 / 12 | 4 / 12 | 2 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 |
Outcome results
Primary
Mean Serum Testosterone Cavg
The objective of the study was to determine the single day serum pharmacokinetic profile for two oral formulations of T-esters (one TE and one TU formulation) administered once- and twice-daily to hypogonadal men.
Time frame: Concentrations at -0.5, 0, 1, 2, 4, 8, 12, 13, 14, 16, 20, 24 and 34 hours post dose
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Testosterone Enanthate and Testosterone Undecanoate | Mean Serum Testosterone Cavg | TE Period 1 400 mg QD | 293 ng/dL | Standard Deviation 148 |
| Testosterone Enanthate and Testosterone Undecanoate | Mean Serum Testosterone Cavg | TU Period 2 200 mg QD | 246 ng/dL | Standard Deviation 77 |
| Testosterone Enanthate and Testosterone Undecanoate | Mean Serum Testosterone Cavg | TU Period 3 100 mg BID | 281 ng/dL | Standard Deviation 89 |
| Testosterone Enanthate and Testosterone Undecanoate | Mean Serum Testosterone Cavg | TU Period 4 200 mg BID | 385 ng/dL | Standard Deviation 132 |
| Testosterone Enanthate and Testosterone Undecanoate | Mean Serum Testosterone Cavg | TE Period 5 400 mg BID | 316 ng/dL | Standard Deviation 167 |
Secondary
Mean Serum Dihydrotestosterone Cmax
The objective of the study was to determine the single day serum pharmacokinetic profile for two oral formulations of T-esters (one TE and one TU formulation) administered once- and twice-daily to hypogonadal men.
Time frame: 24 hours post-dose in each period
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Testosterone Enanthate and Testosterone Undecanoate | Mean Serum Dihydrotestosterone Cmax | TE Period 1 400 mg QD | 140 ng/dL | Standard Deviation 96 |
| Testosterone Enanthate and Testosterone Undecanoate | Mean Serum Dihydrotestosterone Cmax | TU Period 2 200 mg QD | 122 ng/dL | Standard Deviation 66 |
| Testosterone Enanthate and Testosterone Undecanoate | Mean Serum Dihydrotestosterone Cmax | TU Period 3 100 mg BID | 97.9 ng/dL | Standard Deviation 51.2 |
| Testosterone Enanthate and Testosterone Undecanoate | Mean Serum Dihydrotestosterone Cmax | TU Period 4 200 mg BID | 114 ng/dL | Standard Deviation 58 |
| Testosterone Enanthate and Testosterone Undecanoate | Mean Serum Dihydrotestosterone Cmax | TE Period 5 400 mg BID | 127 ng/dL | Standard Deviation 81 |