A Study of the Effect of Topical Testosterone Replacement Therapy on Blood Pressure in Adult Male Participants With Hypogonadism

Study Overview
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Brief Summary
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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.

Official Title
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24-Hour Ambulatory Blood Pressure Monitoring Study in Hypogonadal Men Receiving Testosterone Replacement Therapy

Conditions
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Hypogonadism

Intervention / Treatment
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* Drug: AndroGel 1.62%


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AndroGel 1.62%<br>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. | Drug: AndroGel 1.62%<br>* 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.<br>* Other names: Testosterone gel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | Baseline, Week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypogonadism, Testosterone Replacement Therapy, AndroGel