Hypogonadism
Conditions
Keywords
Healthy Adult Males
Brief summary
Evaluation of pharmacokinetics of subcutaneous testosterone enanthate
Detailed description
Evaluation of pharmacokinetics and safety profile of testosterone enanthate injected subcutaneously via auto-injector in healthy male volunteers
Interventions
COMBINATION_PRODUCTTestosterone enanthate auto-injector
Randomization then administration of combination product study medication according to group assignment
Sponsors
Antares Pharma Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
The dose assignment was random among the enrolled participants.
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy adult male subjects, 18-55 years of age, inclusive, at the time of signing the informed consent; * Body weight ≥50 kg and body mass index within the range 19-30 kg/m2, inclusive, at screening; * Medically healthy subjects with clinically insignificant screening and check-in results (medical history, 12-lead electrocardiogram \[ECG\], physical examination, and laboratory tests); and * Subjects who are able to understand and are willing and able to give their signed informed consent before any trial-related procedures are performed.
Exclusion criteria
* Currently diagnosed or a history of asthma, urticarial, angioedema, anaphylaxis, atopic dermatitis, clinically significant abnormality of skin of the abdomen, cancer, diabetes, or any other clinically significant cardiovascular, respiratory, metabolic, renal, hepatic, gastrointestinal, hematological, dermatological, venereal, neurological, psychiatric, or other major disorders; * History of benign prostate hypertrophy (BPH), prostate cancer, or abnormal prostate specific antigen (PSA) values; * PSA level \> 3 ng/ml at screening; * Presence or history of gastrointestinal, hepatic or renal disease, or any other condition (including surgery) known to interfere with the absorption, distribution, metabolism, or excretion of medicines; * Systolic blood pressure outside the range of 90 to 140 mmHg, diastolic blood pressure outside the range of 40 to 90 mmHg, and/or pulse rate outside the range of 40 to 100 beats per minute after one repeat at screening or check-in; * Abnormal ECG at screening as judged by the Investigator; * History of clinically significant drug and/or food allergies as determined by the Investigator; * Allergy to sesame, sesame oil, or a history of hypersensitivity or idiosyncratic reaction to compounds related to the study drug * Subjects undergoing current treatment with other androgens (i.e. dehydroepiandrosterone \[DHEA\]), anabolic steroids, other sex hormones, or drugs that interfere with the metabolism of testosterone (i.e. opioids, anastrozole, clomiphene, dutasteride, finasteride, flutamide, ketoconazole, spironolactone, and testolactone); * Subjects treated within the past 12 months with estrogens, gonadotropin releasing hormone (GnRH) agonists, or growth hormone; * Prescription, over the counter medications, vitamins, herbal and dietary supplements taken within 7 days or 5 half-lives (whichever is longer) prior to the dose of study medication and duration of the study; * Positive screen for human immunodeficiency virus (HIV), hepatitis B, and/or hepatitis C at screening; * Positive urine screen for drugs of abuse (amphetamine, barbiturates, benzodiazepines, cocaine, marijuana, methadone, methamphetamines, oxycodone, and opiates) or positive breath alcohol test at screening and check-in
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Concentration (Cmax) for Serum Testosterone and Testosterone Enanthate | Maximum serum concentrations occurring during an 8 days study window | Cmax = Maximum blood concentration (ng/dL) of TT=Total Testosterone and TE=Testosterone Enanthate |
| Area Under the Concentration-time Curve From Time Zero to Time t | 168 hrs | AUC(0-168h) (ng⋅hr/dL) = area under the concentration-time curve from time zero to Day 8 (1 week); |
| Area Under the Concentration-time Curve From Time Zero to Infinity | time zero to infinity | AUC(0-inf) (ng⋅hr/dL) = area under the concentration-time curve from time zero to infinity |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Maximum Concentration (Tmax)(hr) | The sample time of Cmax during a 168 hour sampling interval | tmax = Time to reach maximum concentration |
| Vd/F (L) | 168 hours | Vd/F (L) = Apparent volume of distribution |
| Half-life (t 1/2)(hr) | 168 hours | t 1/2 = Half-life is the time required for a concentration to reduce to half its initial value |
| Clearance CL/F (L/hr) | 168 hours | Clearance - volume of plasma from which TT/TE is completely removed per unit time |
Countries
United States
Participant flow
Recruitment details
Pharmacokinetics of single doses of Testosterone Enanthate administered via a drug-auto injector combination product in Healthy Male Subjects
Pre-assignment details
Two dose groups, Testosterone Enanthate 50 mg and Testosterone Enanthate 200 mg , were evaluated in parallel with 6 subjects in each dose group.
Participants by arm
| Arm | Count |
|---|---|
| Testosterone Enanthate 50 mg Testosterone enanthate auto-injector 50 mg | 6 |
| Testosterone Enanthate 200 mg Testosterone enanthate auto-injector 200 mg | 6 |
| Total | 12 |
Baseline characteristics
| Characteristic | Testosterone Enanthate 50 mg | Testosterone Enanthate 200 mg | Total |
|---|---|---|---|
| Age, Continuous | 38.0 years STANDARD_DEVIATION 11.54 | 37.5 years STANDARD_DEVIATION 10.84 | 37.8 years STANDARD_DEVIATION 10.68 |
| Region of Enrollment United States | 6 participants | 6 participants | 12 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 2 / 6 | 1 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 |
Outcome results
Primary
Area Under the Concentration-time Curve From Time Zero to Infinity
AUC(0-inf) (ng⋅hr/dL) = area under the concentration-time curve from time zero to infinity
Time frame: time zero to infinity
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Testosterone Enanthate 50 mg | Area Under the Concentration-time Curve From Time Zero to Infinity | TT | 279062.2 (ng⋅hr/dL) | Standard Deviation 35973.32 |
| Testosterone Enanthate 50 mg | Area Under the Concentration-time Curve From Time Zero to Infinity | TE | NA (ng⋅hr/dL) | — |
| Testosterone Enanthate 200 mg | Area Under the Concentration-time Curve From Time Zero to Infinity | TT | 362627.4 (ng⋅hr/dL) | Standard Deviation 138773.09 |
| Testosterone Enanthate 200 mg | Area Under the Concentration-time Curve From Time Zero to Infinity | TE | 62497.5 (ng⋅hr/dL) | Standard Deviation 24618.09 |
Primary
Area Under the Concentration-time Curve From Time Zero to Time t
AUC(0-168h) (ng⋅hr/dL) = area under the concentration-time curve from time zero to Day 8 (1 week);
Time frame: 168 hrs
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Testosterone Enanthate 50 mg | Area Under the Concentration-time Curve From Time Zero to Time t | TT | 103731.5 (ng⋅hr/dL) | Standard Deviation 12591.81 |
| Testosterone Enanthate 50 mg | Area Under the Concentration-time Curve From Time Zero to Time t | TE | 6122.2 (ng⋅hr/dL) | Standard Deviation 929.12 |
| Testosterone Enanthate 200 mg | Area Under the Concentration-time Curve From Time Zero to Time t | TT | 176112.8 (ng⋅hr/dL) | Standard Deviation 47349.64 |
| Testosterone Enanthate 200 mg | Area Under the Concentration-time Curve From Time Zero to Time t | TE | 33535.5 (ng⋅hr/dL) | Standard Deviation 9977.18 |
Primary
Maximum Concentration (Cmax) for Serum Testosterone and Testosterone Enanthate
Cmax = Maximum blood concentration (ng/dL) of TT=Total Testosterone and TE=Testosterone Enanthate
Time frame: Maximum serum concentrations occurring during an 8 days study window
Population: Healthy normal male volunteers
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Testosterone Enanthate 50 mg | Maximum Concentration (Cmax) for Serum Testosterone and Testosterone Enanthate | Serum testosterone | 773.7 ng/dL | Standard Deviation 121.26 |
| Testosterone Enanthate 50 mg | Maximum Concentration (Cmax) for Serum Testosterone and Testosterone Enanthate | Serum testosterone enanthate | 49.25 ng/dL | Standard Deviation 6.9 |
| Testosterone Enanthate 200 mg | Maximum Concentration (Cmax) for Serum Testosterone and Testosterone Enanthate | Serum testosterone | 1487.0 ng/dL | Standard Deviation 405.34 |
| Testosterone Enanthate 200 mg | Maximum Concentration (Cmax) for Serum Testosterone and Testosterone Enanthate | Serum testosterone enanthate | 267.33 ng/dL | Standard Deviation 75.77 |
Secondary
Clearance CL/F (L/hr)
Clearance - volume of plasma from which TT/TE is completely removed per unit time
Time frame: 168 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Testosterone Enanthate 50 mg | Clearance CL/F (L/hr) | TT | 18.07 L/hr | Standard Deviation 2.33 |
| Testosterone Enanthate 50 mg | Clearance CL/F (L/hr) | TE | NA L/hr | — |
| Testosterone Enanthate 200 mg | Clearance CL/F (L/hr) | TT | 60.46 L/hr | Standard Deviation 21.21 |
| Testosterone Enanthate 200 mg | Clearance CL/F (L/hr) | TE | 352.84 L/hr | Standard Deviation 127.58 |
Secondary
Half-life (t 1/2)(hr)
t 1/2 = Half-life is the time required for a concentration to reduce to half its initial value
Time frame: 168 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Testosterone Enanthate 50 mg | Half-life (t 1/2)(hr) | TT | 261.73 hours | Standard Deviation 99.04 |
| Testosterone Enanthate 50 mg | Half-life (t 1/2)(hr) | TE | NA hours | — |
| Testosterone Enanthate 200 mg | Half-life (t 1/2)(hr) | TT | 131.75 hours | Standard Deviation 28.05 |
| Testosterone Enanthate 200 mg | Half-life (t 1/2)(hr) | TE | 133.00 hours | Standard Deviation 67.85 |
Secondary
Time to Maximum Concentration (Tmax)(hr)
tmax = Time to reach maximum concentration
Time frame: The sample time of Cmax during a 168 hour sampling interval
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Testosterone Enanthate 50 mg | Time to Maximum Concentration (Tmax)(hr) | TT | 40.51 hours | Standard Deviation 52.95 |
| Testosterone Enanthate 50 mg | Time to Maximum Concentration (Tmax)(hr) | TE | 82.01 hours | Standard Deviation 53.88 |
| Testosterone Enanthate 200 mg | Time to Maximum Concentration (Tmax)(hr) | TT | 19.00 hours | Standard Deviation 7.75 |
| Testosterone Enanthate 200 mg | Time to Maximum Concentration (Tmax)(hr) | TE | 74.00 hours | Standard Deviation 57.01 |
Secondary
Vd/F (L)
Vd/F (L) = Apparent volume of distribution
Time frame: 168 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Testosterone Enanthate 50 mg | Vd/F (L) | TT | 6655.8 Liters | Standard Deviation 1702.04 |
| Testosterone Enanthate 50 mg | Vd/F (L) | TE | NA Liters | — |
| Testosterone Enanthate 200 mg | Vd/F (L) | TE | 62366.4 Liters | Standard Deviation 23950.96 |
| Testosterone Enanthate 200 mg | Vd/F (L) | TT | 10959.5 Liters | Standard Deviation 2040.99 |