Hypogonadism, Male
Conditions
Keywords
Low T
Brief summary
The purpose of this study is to evaluate changes in vascular parameters and the prevalence of side effects in subjects receiving 1 cc (200mg) every 2 weeks intramuscular (IM) of Testosterone Cypionate versus subjects receiving 11mg three times daily (TID) Natesto to participant with clinical hypogonadism.
Detailed description
Administration of exogenous testosterone as efficacious treatment for male hypogonadism has been part of medical practice for more than 50 years. Testosterone replacement therapy (TRT) is becoming more widely available and has seen a greater than three-fold increase in use in men 40 years and older. Current delivery systems of TRT include transdermal gels and patches, intranasal gels (currently marketed as Natesto), injection therapy, and long acting subcutaneous pellets. Natesto is a short-acting formulation of testosterone delivered intranasally to men diagnosed with low T. This has the potential to avoid side effects related to TRT that are commonly seen with other delivery methods, namely polycythemia, acne, male-pattern hair loss, azoospermia and hyperestrogenemia. Testosterone Cypionate injections are the most common form of TRT in the USA. Testosterone Cypionate has many reported side effects, the most common being polycythemia, gynecomastia, hair loss, acne, decreased spermatogenesis, and testicular atrophy. In a multicenter retrospective study, it has been shown that the prevalence of polycythemia in men on testosterone replacement (injections) was 11.2%. In this study, we will compare hematocrit changes caused by treatment with Testosterone Cypionate and Natesto in a parallel arm, randomized study. To date, there have been no direct head-to-haed comparisons of these formulations. We hypothesize that the short-acting pharmacokinetics of Natesto more closely resembles the natural pulsatility of testosterone and therefore can avoid side effects traditionally seen in long-acting, exogenous testosterone formulations
Interventions
DRUGTestosterone Cypionate 200 Mg/ML
Participants in this group will receive intramuscular testosterone cypionate injections of 1 cc (200mg) once every 14 days for four months.
DRUGIntranasal Testosterone
Participant in this group will receive Intranasal testosterone administered using a multi-dose dispenser, as two or three daily doses (5.5 mg per nostril, 11.0 mg single dose) for 4 consecutive months,
Sponsors
Acerus Pharmaceuticals Corporation
University of Miami
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Voluntarily sign and date the study consent form(s), which have been approved by an Institutional Review Board (IRB). Written consent must be obtained prior to the initiation of any study procedures. 2. Documented diagnosis of primary hypogonadism (congenital or acquired) or hypogonadotropic hypogonadism (congenital or acquired). 3. Serum total testosterone \< 300 ng/dL on 2 measurements 4. Naïve to androgen replacement or has discontinued current treatment and completed a washout of 4 months following androgen treatment. 5. Men deemed to be candidates for TRT based on the results of a medical history, physical examination, vital signs, laboratory profile and a 12-lead electrocardiogram (ECG).
Exclusion criteria
1. History of significant sensitivity or allergy to androgens, or product excipients. 2. Clinically significant findings in the pre-study examinations including abnormal breast examination requiring follow-up, abnormal ECG. 3. Abnormal prostate digital rectal examination (DRE) with palpable nodule(s) 4. Body mass index (BMI) ≥ 40 kg/m2. 5. Clinically significant abnormal laboratory value, in the opinion of the investigator, in serum chemistry, hematology, or urinalysis including but not limited to: 1. Baseline hemoglobin \> 16 g/dL or Hematocrit (HCT) 48% 2. Prostate Specific Antigen (PSA) \> 4 ng/mL 6. History of seizures or convulsions, including febrile, alcohol or drug withdrawal seizures. 7. History of any clinically significant illness, infection, or surgical procedure within 4 weeks prior to study drug administration. 8. History of stroke or myocardial infarction within the past 5 years. 9. History of, or current or suspected, prostate or breast cancer. 10. History of diagnosed, severe, untreated, obstructive sleep apnea. 11. History of abuse of alcohol or any drug substance in the opinion of the investigator within the previous 2 years. 12. Donation or loss of 550 mL or more blood volume (including plasmapheresis) or receipt of a transfusion of any blood product within 12 weeks prior to the start of treatment. 13. Inadequate venous access for collection of serial blood samples required for pharmacokinetic profiles. 14. Receipt of any subcutaneous testosterone pellets within the last 6 months. 15. Inability to understand and provide written informed consent for the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hematocrit (Hct) Levels. | Baseline to 4 months | Changes in serum Hematocrit levels will be assessed in percentage |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hormone Levels | Baseline to 4 months | Change in serum hormone levels including Testosterone, 17-Hydroxyprogesterone (17-OHP) assessed in ng/dL. |
| Change in PSA Levels | Baseline to 4 months | Change in serum Prostate Specific Antigen (PSA) levels will be assessed in ng/mL. |
| Change in Estradiol Levels | Baseline to 4 months | Change in serum estradiol levels will be assessed in pg/mL. |
| Changes in IIEF-6 Score | Baseline to 4 months | The International Index of Erectile Function (IIEF)-6 is a 6-item subdomain self-evaluation questionnaire of erectile function. Each item is scored from 0-5 with the total score ranging from 0-30 with the higher score indicating better erectile function. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Testosterone Cypionate Group Participants in this group will receive the intramuscular Testosterone Cypionate intervention for four months
Testosterone Cypionate 200 Mg/ML: Participants in this group will receive intramuscular testosterone cypionate injections of 1 cc (200mg) once every 14 days for four months. | 41 |
| Natesto Group Participants in this group will receive the intranasal testosterone (Natesto) intervention for four months.
Intranasal Testosterone: Participant in this group will receive Intranasal testosterone administered using a multi-dose dispenser, as two or three daily doses (5.5 mg per nostril, 11.0 mg single dose) for 4 consecutive months, | 40 |
| Total | 81 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 5 |
| Overall Study | Lost to Follow-up | 6 | 6 |
| Overall Study | Withdrawal by Subject | 2 | 6 |
Baseline characteristics
| Characteristic | Natesto Group | Total | Testosterone Cypionate Group |
|---|---|---|---|
| Age, Continuous | 48.2 years STANDARD_DEVIATION 10.89 | 48.33 years STANDARD_DEVIATION 11.32 | 48.46 years STANDARD_DEVIATION 11.86 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 22 Participants | 51 Participants | 29 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants | 30 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 9 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) White | 29 Participants | 69 Participants | 40 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 40 Participants | 81 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 41 | 0 / 40 |
| other Total, other adverse events | 2 / 41 | 5 / 40 |
| serious Total, serious adverse events | 0 / 41 | 0 / 40 |
Outcome results
Primary
Change in Hematocrit (Hct) Levels.
Changes in serum Hematocrit levels will be assessed in percentage
Time frame: Baseline to 4 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Testosterone Cypionate Group | Change in Hematocrit (Hct) Levels. | 3.0 percentage of hematocrit |
| Natesto Group | Change in Hematocrit (Hct) Levels. | -0.6 percentage of hematocrit |
Secondary
Change in Estradiol Levels
Change in serum estradiol levels will be assessed in pg/mL.
Time frame: Baseline to 4 months
Population: In the Testosterone Cypionate group, seven participants did not have estradiol laboratory tests performed due to protocol non-compliance. in the Natesto group three participants did not have estradiol laboratory tests performed due to protocol non-compliance.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Testosterone Cypionate Group | Change in Estradiol Levels | 22.9 pg/mL |
| Natesto Group | Change in Estradiol Levels | 1.1 pg/mL |
Secondary
Change in Hormone Levels
Change in serum hormone levels including Testosterone, 17-Hydroxyprogesterone (17-OHP) assessed in ng/dL.
Time frame: Baseline to 4 months
Population: In the Natesto group, three participants group did not have Testosterone labs collected and four did not have 17-OHP laboratory tests collected due to protocol non-compliance. in the Testosterone Cypionate group, Nine group did not have 17-OHP labs collected due to protocol non-compliance.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Testosterone Cypionate Group | Change in Hormone Levels | 17-OHP | -39.8 ng/dL |
| Testosterone Cypionate Group | Change in Hormone Levels | Testosterone | 511 ng/dL |
| Natesto Group | Change in Hormone Levels | 17-OHP | -8.8 ng/dL |
| Natesto Group | Change in Hormone Levels | Testosterone | 283 ng/dL |
Secondary
Change in PSA Levels
Change in serum Prostate Specific Antigen (PSA) levels will be assessed in ng/mL.
Time frame: Baseline to 4 months
Population: Six participants in the Testosterone Cypionate group did not have PSA laboratory tests performed due to protocol non-compliance. Six participants in the Natesto group did not have PSA laboratory tests performed due to protocol non-compliance.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Testosterone Cypionate Group | Change in PSA Levels | 0.6 ng/mL |
| Natesto Group | Change in PSA Levels | 0.05 ng/mL |
Secondary
Changes in IIEF-6 Score
The International Index of Erectile Function (IIEF)-6 is a 6-item subdomain self-evaluation questionnaire of erectile function. Each item is scored from 0-5 with the total score ranging from 0-30 with the higher score indicating better erectile function.
Time frame: Baseline to 4 months
Population: In the Testosterone Cypionate group, fourteen participants did not complete the IIEF-6 questionnaire due to protocol non-compliance. In the Natesto group thirteen participants did not complete the IIEF-6 questionnaire due to protocol non-compliance.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Testosterone Cypionate Group | Changes in IIEF-6 Score | 4.8 score on a scale |
| Natesto Group | Changes in IIEF-6 Score | 0.2 score on a scale |