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

Hypogonadism Clinical Trial

Official title:

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 Administration With Marketed Testosterone Products

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04456296
• Other study ID #: EN3000-101
• Status: Completed
• Phase: Phase 4
• Start date: June 30, 2020
• Est. completion date: July 12, 2023

Study information

• Verified date: July 2023
• Source: Endo Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Testosterone is the principal androgen produced by the male testes. 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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 676
• Est. completion date: July 12, 2023
• Est. primary completion date: July 12, 2023
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Have a diagnosis of primary hypogonadism or hypogonadotropic hypogonadism.

2. 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

3. Be naïve to androgen replacement or washout of 12 weeks following intramuscular androgen injections; 4 weeks following topical or buccal, nasal, or oral androgens.

4. 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.

5. Be judged to be in good health.

6. Participants enrolled in the Testim or Fortesta treatment arms: take necessary precautions to avoid skin-to-skin contact and potential transfer and if male use effective contraception.

7. Be willing and able to cooperate with the requirements of the study.

Exclusion Criteria:

1. 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).

2. Has a history of significant sensitivity or allergy to the study drugs, including androgens, or product excipients.

3. 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.

4. Has clinically significant changes in any medications (including dosages) or medical conditions in the 28 days prior to screening

5. Is not on a stable medication regimen for at least 3 months for the treatment of a chronic condition.

6. Has had a cardiovascular and/or cerebrovascular event within the last 6 months.

7. Needs blood pressure cuff size larger than 50 centimeters.

8. Works a night shift or performs heavy manual labor.

9. 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.

10. 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.

1. 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.

2. 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.

3. Uses nutraceuticals or homeopathic compounds.

11. Has a history of drug or alcohol abuse within 6 months prior to study drug administration.

12. Has untreated moderate to severe depression.

13. Has any skin lesions/cuts/injury at the application site.

14. Has suspected reversible hypogonadism.

15. Donated blood or blood products or experienced significant blood loss within 90 days prior to study drug administration.

16. Intends to conceive at any time during the study.

17. Donated bone marrow within 6 months prior to study drug administration.

18. Has participated in a previous investigational study or received treatment with an investigational product within 30 days of screening.

19. Has a diagnosis of, is undergoing therapy for, or has received therapy for a hematologic malignancy in the 5 years prior to screening.

20. Has a history of substance abuse or is taking any substance of abuse (Note:

participants on a stable dose of any medications that have been prescribed by a healthcare practitioner for a properly documented medical condition are exempt).

21. Abnormal electrocardiogram (ECG) (QT prolongation with QTc =450 milliseconds).

22. Has evidence of abnormalities on physical examination, vital signs, ECG, or clinical lab values, unless judged to be clinically insignificant by the investigator

23. Has any other condition that might indicate the participant to be unsuitable for the study.

Related Conditions & MeSH terms

• Hypogonadism
• Hypogonadism, Male
• Hypogonadotropic Hypogonadism

Intervention

Drug:
• Aveed Injectable Product
Testosterone undecanoate administered by intramuscular injections.
• Fortesta
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).
• Testim
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).

Locations

Country	Name	City	State
United States	Endo Clinical Trial Site #13	Bala-Cynwyd	Pennsylvania
United States	Endo Clinical Trial Site #32	Bell Gardens	California
United States	Endo Clinical Trial Site #30	Beverly Hills	Florida
United States	Endo Clinical Trial Site #8	Birmingham	Alabama
United States	Endo Clinical Trial Site #12	Boynton Beach	Florida
United States	Endo Clinical Trial Site #34	Boynton Beach	Florida
United States	Endo Clinical Trial Site #33	Canoga Park	California
United States	Endo Clinical Trial Site #6	Charlottesville	Virginia
United States	Endo Clinical Trial Site #16	Chicago	Illinois
United States	Endo Clinical Trial Site #5	Dayton	Ohio
United States	Endo Clinical Trial Site #35	East Orange	New Jersey
United States	Endo Clinical Trial Site #29	Fleming Island	Florida
United States	Endo Clinical Trial Site #9	Garden City	New York
United States	Endo Clinical Trial Site #27	Glen Burnie	Maryland
United States	Endo Clinical Trial Site #19	Houston	Texas
United States	Endo Clinical Trial Site #20	Houston	Texas
United States	Endo Clinical Trial Site #31	Houston	Texas
United States	Endo Clinical Trial Site #2	Miami	Florida
United States	Endo Clinical Trial Site #26	Miami	Florida
United States	Endo Clinical Trial Site #28	Miami	Florida
United States	Endo Clinical Trial Site #10	Miami Beach	Florida
United States	Endo Clinical Trial Site #18	Miami Gardens	Florida
United States	Endo Clinical Trial Site #21	Missouri City	Texas
United States	Endo Clinical Trial Site #7	New York	New York
United States	Endo Clinical Trial Site #15	North Little Rock	Arkansas
United States	Endo Clinical Trial Site #3	Oviedo	Florida
United States	Endo Clinical Trial Site #4	Pembroke Pines	Florida
United States	Endo Clinical Trial Site #11	Pompano Beach	Florida
United States	Endo Clinical Trial Site #14	Rutland	Vermont
United States	Endo Clinical Trial Site #1	San Antonio	Texas
United States	Endo Clinical Trial Site #17	Towson	Maryland
United States	Endo Clinical Trial Site #22	Tucson	Arizona
United States	Endo Clinical Trial Site #24	Virginia Beach	Virginia
United States	Endo Clinical Trial Site #23	West Palm Beach	Florida
United States	Endo Clinical Trial Site #25	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Endo Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline in 24-Hour Average Systolic Ambulatory Blood Pressure		Baseline (Day 1), Week 16
Secondary	Change from Baseline in 24-Hour Average Arterial Pressure		Baseline (Day 1), Week 16
Secondary	Change from Baseline in 24-Hour Average Systolic Blood Pressure		Baseline (Day 1), Week 16
Secondary	Change from Baseline in 24-Hour Average Diastolic Blood Pressure		Baseline (Day 1), Week 16
Secondary	Change from Baseline in 24-Hour Average Heart Rate		Baseline (Day 1), Week 16
Secondary	Change from Baseline in 24-Hour Average Pulse Pressure		Baseline (Day 1), Week 16
Secondary	Percent of Participants Taking New Antihypertensive Medications		Week 16
Secondary	Percent of Participants with Dose Increases From Baseline in Antihypertensive Medications		Week 16