Hypogonadism
Conditions
Keywords
Hypogonadism, Testosterone Replacement Therapy, AndroGel
Brief summary
Hypogonadism is an endocrine disorder characterized by absent or deficient testosterone levels along with signs and symptoms of androgen deficiency, including delayed development or regression of sexual characteristics, impaired sexual function and sense of well-being, depressed mood, decreased muscle strength associated with loss of muscle mass and reduced bone mineral density. AndroGel 1.62% has demonstrated its ability to increase total testosterone levels in the blood by absorption of testosterone through the skin when applied topically. This study evaluated the effect of AndroGel 1.62% on systolic blood pressure using ambulatory blood pressure monitoring in hypogonadal men who used testosterone replacement therapy. AndroGel 1.62% is a drug used for the treatment of hypogonadism, which is associated with low or no testosterone. This was an open-label study which means that both the study doctor and study participants knew what drug and what dose is being used. All participants in this study were in the same group, called a treatment arm. Adult male participants with hypogonadism were enrolled and received AndroGel 1.62%. This was a multi-center study with 190 participants enrolled (initially planned) in approximately 45 sites in the United States to yield 171 subjects in the per protocol (PP) population. A blinded sample size re-estimation (BSSR) was performed when around 70% of the planned subjects in the PP population had completed the end of treatment visit. Sample size was increased at BSSR and 246 participants were actually enrolled. Participants received daily topical gel doses of AndroGel 1.62% for approximately 16 weeks. There may have been a higher burden for participants in this study compared to standard of care. Participants attended 8 study visits during the course of the study at a hospital or clinic and received 2 study phone calls. The effect of the treatment was checked by medical assessments, blood tests (including pharmacokinetic sampling), and 24-hour blood pressure monitors.
Interventions
DRUGAndroGel 1.62%
AndroGel 1.62% was packaged in pump bottles with quantities sufficient to accommodate study design and could have been dose adjusted between a minimum of 20.25 mg of T (1 pump actuation) and a maximum of 81.0 mg of testosterone (4 pump actuations). For the first study drug administration at the Day 1 Visit, and also at Week 2, Week 4, Week 16 ambulatory blood pressure monitoring (ABPM,) and End of Treatment Visits, participants applied the study drug while on site so that the site staff could observe the proper administration of study drug. If participants forgot to apply their AndroGel 1.62% dose at their regularly scheduled dosing time, they were to take the next dose at the next dosing time.
Sponsors
AbbVie
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of hypogonadism with the presence of at least one of the following symptoms that may be related to low testosterone values and is/are consistent with hypogonadism: * Decreased sexual desire or libido * Decreased spontaneous erections (e.g. morning erections) * Decreased energy or fatigue/feeling tired * Low mood or depressed mood * Loss of body (axillary and pubic) hair or reduced shaving * Hot flashes AND * Confirmed by 2 serum testosterone levels \< 300 ng/dL by blood samples drawn at least 48 hours apart. These samples should be obtained between 5 am and 11 am local time. * Blood pressure \>100/60 mmHg and \<140/90 mmHg
Exclusion criteria
* Unprovoked deep vein thrombosis (DVT), unprovoked pulmonary embolism (PE), or known thrombophilia * Polycythemia vera or secondary polycythemia, such as polycythemia due to untreated sleep apnea or severe chronic obstructive pulmonary disease * Prostate or breast cancer * Any active malignancy * Clinically significant medical conditions or any other reason that the investigator determines would interfere with participation in this study or would make the participant an unsuitable candidate to receive study drug * Work night shifts or is otherwise required to perform strenuous manual labor while wearing the Ambulatory Blood Pressure Monitor (ABPM).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to End of Treatment (EOT) in 24-hour Average Systolic Blood Pressure (SBP) | Baseline, Week 16 | Systolic blood pressure was measured by the ambulatory blood pressure monitoring (ABPM) procedure. Measurements were obtained from participants using a portable data-monitoring device. The ABPM procedure was performed over a 24-hour period across 2 days and included ABPM device application by site (1st Day) and ABPM device removal by site (2nd Day). |
Countries
United States
Participant flow
Pre-assignment details
All enrolled participants
Participants by arm
| Arm | Count |
|---|---|
| AndroGel 1.62% AndroGel 1.62% was applied topically once daily in the morning beginning at the Day 1 Visit after confirmed valid ambulatory blood pressure monitoring (ABPM) assessment and was applied at approximately the same time each day after that during the study for approximately 16 weeks. The starting dose of AndroGel 1.62% was 40.5 mg of T (2 pump actuations, applied to the upper arms and shoulders) and was titrated up or down by 20.25 mg or remained the same as assessed by morning serum T levels at Weeks 2 and 4. | 246 |
| Total | 246 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 7 |
| Overall Study | COVID-19 infection | 1 |
| Overall Study | Lost to Follow-up | 9 |
| Overall Study | Other, not specified | 20 |
| Overall Study | Withdrew consent | 5 |
Baseline characteristics
| Characteristic | AndroGel 1.62% |
|---|---|
| Age, Continuous | 57.6 years STANDARD_DEVIATION 10.35 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 Participants |
| Race/Ethnicity, Customized Asian | 5 Participants |
| Race/Ethnicity, Customized Black or African American | 29 Participants |
| Race/Ethnicity, Customized Multiple | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized White | 209 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 246 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 246 |
| other Total, other adverse events | 43 / 246 |
| serious Total, serious adverse events | 8 / 246 |
Outcome results
Primary
Change From Baseline to End of Treatment (EOT) in 24-hour Average Systolic Blood Pressure (SBP)
Systolic blood pressure was measured by the ambulatory blood pressure monitoring (ABPM) procedure. Measurements were obtained from participants using a portable data-monitoring device. The ABPM procedure was performed over a 24-hour period across 2 days and included ABPM device application by site (1st Day) and ABPM device removal by site (2nd Day).
Time frame: Baseline, Week 16
Population: Per protocol set analysis: all participants who received at least 1 dose of study drug, were at least 85% compliant to study drug, and had valid Baseline and end of treatment systolic ABPM data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AndroGel 1.62% | Change From Baseline to End of Treatment (EOT) in 24-hour Average Systolic Blood Pressure (SBP) | 1.9 mmHg | Standard Deviation 8.99 |
Comparison: The primary endpoint of change from Baseline to End of Treatment (EOT) in average 24-hour SBP was evaluated using a linear regression model with change in average 24-hour SBP from Baseline to EOT as the dependent variable, centralized baseline average 24-hour SBP, ongoing medical history of hypertension, and pooled study center as covariates in the per protocol population.95% CI: [0.63, 3.13]