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

NCT04456296 | Completed Phase 4 Results FDA Drug

• 1 other identifier: EN3000-101
• Study Type: interventional
• Target: 673
• Locations: 1 country
• Sites: 35

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.

Conditions

Hypogonadism; Hypogonadism, Male; Hypogonadotropic Hypogonadism

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in 24-Hour Average Systolic Ambulatory Blood Pressure to End of Study (EOS)

  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.

  Baseline (Day 1), EOS Visit: up to Day 107 for the Aveed Arm, and up to Day 114 for Fortesta and Testim Arms

Secondary Outcomes (6)

• 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

Study Arms (3)

AVEED (Testosterone Undecanoate Injection)

ACTIVE COMPARATOR

Fixed dosage level of 750 milligrams (mg)/3 milliliters (mL) administered by intramuscular injections.

Drug: Aveed Injectable Product

FORTESTA (Testosterone Gel)

ACTIVE COMPARATOR

40 mg once daily topical gel administration.

Drug: Fortesta

TESTIM (Testosterone Gel)

ACTIVE COMPARATOR

50 mg once daily topical gel administration.

Drug: Testim

Interventions

Aveed Injectable Product DRUG

Testosterone undecanoate administered by intramuscular injections.

Also known as: Testosterone undecanoate

AVEED (Testosterone Undecanoate Injection)

Fortesta DRUG

Testosterone gel administered topically. The daily dose of the study drug will be titrated for each participant, according to approved dosage and administration instructions, until the circulating testosterone concentrations of the participant reaches normal concentrations (300-1000 ng/dL).

Also known as: Testosterone gel

FORTESTA (Testosterone Gel)

Testim DRUG

Testosterone gel administered topically. The daily dose of the study drug will be titrated for each participant, according to approved dosage and administration instructions, until the circulating testosterone concentrations of the participant reaches normal concentrations (300-1000 ng/dL).

Also known as: Testosterone gel

TESTIM (Testosterone Gel)

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• Uses any of the above listed drugs within 5 half lives of the last dose in the past 6 months prior to study drug administration.
• Has received any of the above listed drugs by injection within 30 days or 10 half lives (whichever is longer) prior to study drug administration.
• Uses nutraceuticals or homeopathic compounds which have a known effect on blood pressure.
• Has a history of drug or alcohol abuse within 6 months prior to study drug administration.
• Has untreated moderate to severe depression.

Sponsors & Collaborators

• Endo Pharmaceuticals: lead

Study Sites (35)

Endo Clinical Trial Site #8

Birmingham, Alabama, 35235, United States

Location

Endo Clinical Trial Site #22

Tucson, Arizona, 85712, United States

Location

Endo Clinical Trial Site #15

North Little Rock, Arkansas, 72116, United States

Location

Endo Clinical Trial Site #32

Bell Gardens, California, 90201, United States

Location

Endo Clinical Trial Site #33

Canoga Park, California, 91304, United States

Location

Endo Clinical Trial Site #30

Beverly Hills, Florida, 90211, United States

Location

Endo Clinical Trial Site #12

Boynton Beach, Florida, 33435, United States

Location

Endo Clinical Trial Site #34

Boynton Beach, Florida, 33435, United States

Location

Endo Clinical Trial Site #29

Fleming Island, Florida, 32003, United States

Location

Endo Clinical Trial Site #26

Miami, Florida, 33014, United States

Location

Endo Clinical Trial Site #2

Miami, Florida, 33014, United States

Location

Endo Clinical Trial Site #28

Miami, Florida, 33183, United States

Location

Endo Clinical Trial Site #10

Miami Beach, Florida, 33140, United States

Location

Endo Clinical Trial Site #18

Miami Gardens, Florida, 33023, United States

Location

Endo Clinical Trial Site #3

Oviedo, Florida, 32765, United States

Location

Endo Clinical Trial Site #4

Pembroke Pines, Florida, 33027, United States

Location

Endo Clinical Trial Site #11

Pompano Beach, Florida, 33060, United States

Location

Endo Clinical Trial Site #23

West Palm Beach, Florida, 33401, United States

Location

Endo Clinical Trial Site #16

Chicago, Illinois, 60611, United States

Location

Endo Clinical Trial Site #27

Glen Burnie, Maryland, 21061, United States

Location

Endo Clinical Trial Site #17

Towson, Maryland, 21204, United States

Location

Endo Clinical Trial Site #35

East Orange, New Jersey, 07018, United States

Location

Endo Clinical Trial Site #9

Garden City, New York, 11530, United States

Location

Endo Clinical Trial Site #7

New York, New York, 10016, United States

Location

Endo Clinical Trial Site #25

Winston-Salem, North Carolina, 27103, United States

Location

Endo Clinical Trial Site #5

Dayton, Ohio, 45417, United States

Location

Endo Clinical Trial Site #13

Bala-Cynwyd, Pennsylvania, 19004, United States

Location

Endo Clinical Trial Site #19

Houston, Texas, 77036, United States

Location

Endo Clinical Trial Site #31

Houston, Texas, 77084, United States

Location

Endo Clinical Trial Site #20

Houston, Texas, 77087, United States

Location

Endo Clinical Trial Site #21

Missouri City, Texas, 77459, United States

Location

Endo Clinical Trial Site #1

San Antonio, Texas, 78229, United States

Location

Endo Clinical Trial Site #14

Rutland, Vermont, 05701, United States

Location

Endo Clinical Trial Site #6

Charlottesville, Virginia, 22911, United States

Location

Endo Clinical Trial Site #24

Virginia Beach, Virginia, 23462, United States

Location

MeSH Terms

Conditions

Hypogonadism; Eunuchism

Interventions

testosterone undecanoate; Testosterone Propionate; Testosterone

Condition Hierarchy (Ancestors)

Gonadal Disorders; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Androstenols; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Clinical Operations
• Organization: Endo Pharmaceuticals

clinicaltrials@endo.com

800-462-3636

Study Officials

• David Hernandez

  Endo Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2020
• First Posted: July 2, 2020
• Study Start: June 30, 2020
• Primary Completion: July 12, 2023
• Study Completion: July 12, 2023
• Last Updated: March 14, 2025
• Results First Posted: March 14, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP

Locations

US (35)