An Open-Label, Randomized, Parallel-Group, Three Treatment Arm, Multicenter Study on Hypogonadal Males to Evaluate the Effect on 24-Hour Ambulatory Blood Pressure After 16-Week Continuous Treatment With Marketed Testosterone Products
Overview
- Phase
- Phase 4
- Intervention
- Aveed Injectable Product
- Conditions
- Hypogonadism
- Sponsor
- Endo Pharmaceuticals
- Enrollment
- 673
- Locations
- 35
- Primary Endpoint
- Change From Baseline in 24-Hour Average Systolic Ambulatory Blood Pressure to End of Study (EOS)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
Testosterone is the principal androgen produced by the male testes. Male Hypogonadism is the result of inadequate production of testosterone by the Leydig cells of the testes and is reflected by total serum concentrations of testosterone of < 300 nanograms (ng)/deciliters (dL), with no discernible diurnal pattern. The etiology of hypogonadism may be primary or secondary. The treatment of males with primary, and in some cases, secondary hypogonadism includes administration of testosterone.
Testim® and Fortesta® are topical gels that when applied daily help to increase the total testosterone levels in the blood through skin absorption. Aveed® is an injectable form of testosterone treatment and participants randomized to this treatment arm will receive 3 injections over the course of 16 weeks.
This study is designed to evaluate the effect on blood pressure of approved testosterone products (Testim®, Fortesta®, and Aveed®) after 16 weeks of therapy using 24-hour ambulatory blood pressure to reveal shifts in blood pressure levels.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Have a diagnosis of primary hypogonadism or hypogonadotropic hypogonadism.
- •Have a total serum testosterone at screening \< 300 ng/dL based on 2 blood samples obtained at 10 am (+/-2 hours) on 2 separate occasions at least 48 hours apart
- •Be naïve to androgen replacement or washout of 12 weeks following intramuscular androgen injections; 4 weeks following topical or buccal, nasal, or oral androgens.
- •Have a screening blood pressure at rest of less than 140 millimeters of mercury (mm Hg) for systolic blood pressure and less than 90 mm Hg for diastolic blood pressure.
- •Be judged to be in good health.
- •Participants enrolled in the Testim or Fortesta treatment arms: participants agree to take necessary precautions to avoid skin-to-skin contact and potential transfer and if male use effective contraception.
- •Be willing and able to cooperate with the requirements of the study.
Exclusion Criteria
- •Is from a vulnerable population, as defined by the US Code of Federal Regulations (CFR) Title 45, Part 46, Section 46.111(b) and other local and national regulations, including but not limited to, employees (temporary, part-time, full time, etc) or a family member of the research staff conducting the study, or of the sponsor, or of the contract research organization, or of the Institutional Review Board/Independent Ethics Committee (IRB/IEC).
- •Has a history of significant sensitivity or allergy to the study drugs, including androgens, or product excipients.
- •Has a history of or medical examination findings renal, hepatic, neurologic, hematologic, endocrine, oncologic, pulmonary, immunologic, psychiatric conditions, cardiovascular disease/dysrhythmia) or any other condition(s) that restricts study participation.
- •Has clinically significant changes in any medications (including dosages) or medical conditions in the 28 days prior to screening
- •Is not on a stable medication regimen for at least 3 months for the treatment of a chronic condition.
- •Has had a cardiovascular and/or cerebrovascular event within the last 6 months.
- •Needs blood pressure cuff size larger than 50 centimeters.
- •Works a night shift or performs heavy manual labor.
- •Has any known contraindication(s) to active study treatment including, but not limited to: known or suspected carcinoma of the prostate or breast, previous history of cancer (except basal cell carcinoma of the skin) liver disease, active deep vein thrombosis, atrial fibrillation, untreated sleep apnea, or is immune compromised.
- •Uses known inhibitors (for example, ketoconazole) or inducers of cytochrome P450 3A (for example, dexamethasone, phenytoin, rifampin, carbamazepine) of cytochrome P450 3A (CYP3A) within 30 days prior to study drug administration and through the end of the study.
Arms & Interventions
AVEED (Testosterone Undecanoate Injection)
Fixed dosage level of 750 milligrams (mg)/3 milliliters (mL) administered by intramuscular injections.
Intervention: Aveed Injectable Product
FORTESTA (Testosterone Gel)
40 mg once daily topical gel administration.
Intervention: Fortesta
TESTIM (Testosterone Gel)
50 mg once daily topical gel administration.
Intervention: Testim
Outcomes
Primary Outcomes
Change From Baseline in 24-Hour Average Systolic Ambulatory Blood Pressure to End of Study (EOS)
Time Frame: Baseline (Day 1), EOS Visit: up to Day 107 for the Aveed Arm, and up to Day 114 for Fortesta and Testim Arms
The mean change from Baseline to EOS in 24-hour average systolic ambulatory blood pressure, for each treatment group was analyzed using an analysis of covariance (ANCOVA) model with treatment and study center (pooled centers) as fixed effects, Baseline 24-hour average systolic ambulatory blood pressure as covariate. EOS for the Aveed arm was Day 107 and EOS for Fortesta and Testim, was Day 114.
Secondary Outcomes
- Change From Baseline in 24-Hour Average Mean Arterial Pressure (MAP) to EOS(Baseline (Day 1), EOS Visit: up to Day 107 for the Aveed Arm, and up to Day 114 for Fortesta and Testim Arms)
- Change From Baseline in 24-Hour Average Diastolic Ambulatory Blood Pressure to EOS(Baseline (Day 1), EOS Visit: up to Day 107 for the Aveed Arm, and up to Day 114 for Fortesta and Testim Arms)
- Change From Baseline in 24-Hour Average Heart Rate to EOS(Baseline (Day 1), EOS Visit: up to Day 107 for the Aveed Arm, and up to Day 114 for Fortesta and Testim Arms)
- Change From Baseline in 24-Hour Average Pulse Pressure (PP) to EOS(Baseline (Day 1), EOS Visit: up to Day 107 for the Aveed Arm, and up to Day 114 for Fortesta and Testim Arms)
- Percentage of Participants Taking New Antihypertensive Medications(EOS Visit: up to Day 107 for the Aveed Arm, and up to Day 114 for Fortesta and Testim Arms)
- Percentage of Participants With Dose Increase From Baseline in Antihypertensive Medications(EOS Visit: up to Day 107 for the Aveed Arm, and up to Day 114 for Fortesta and Testim Arms)