Clinical Evaluation of Subcutaneous Testosterone Implants in Men With Symptomatic Hypogonadism

Обзор

Introduction: Male hypogonadism is a clinical syndrome associated with significant consequences for health and quality of life. In Brazil, approved testosterone replacement therapy options are limited to injectable formulations and transdermal gels, which are often associated with suboptimal adherence. Subcutaneous testosterone implants, already used in the United States and recommended by international guidelines, represent a promising alternative but are not yet available in Brazil. Objective: To evaluate the efficacy, safety, pharmacokinetics, and quality-of-life impact of 200 mg testosterone implants manufactured in Brazil for the treatment of men with symptomatic hypogonadism. Methods: This is a prospective interventional study conducted at the Division of Urology of the Hospital das Clínicas, University of São Paulo School of Medicine (FMUSP). Thirty cisgender hypogonadal men meeting strict inclusion and exclusion criteria will be enrolled. Participants will receive subcutaneous testosterone implants totaling 800 mg and will be followed for six months. Serial blood sampling will be performed to assess hormonal levels (total and free testosterone, LH, FSH, and PSA) and metabolic parameters (lipid profile, body mass index, and waist circumference). Validated questionnaires, including the IIEF-15, ADAM, and WHOQOL-BREF, will be used to evaluate sexual function, hypogonadal symptoms, quality of life, and patient satisfaction. Outcomes: The primary outcome is the ability of the implants to achieve and maintain therapeutic serum testosterone levels (450-800 ng/dL). Secondary outcomes include pharmacokinetic profile (Cmax, half-life, and mean duration), metabolic effects, changes in quality of life, and treatment adherence. Clinical Significance: This study advances the understanding of a testosterone replacement modality that may offer greater convenience for selected patients and for which data on nationally manufactured products are currently lacking. Over a six-month period, the study will investigate laboratory behavior, clinical impact, and patient satisfaction. Relevance and Impact: This is the first study of its kind conducted in Brazil, combining methodological rigor with a robust design to evaluate the safety and efficacy of domestically manufactured testosterone implants. The methodology incorporates detailed ethical and scientific criteria, ensuring high-quality data. The results may support regulatory and clinical decision-making, benefiting patients and potentially contributing to the Brazilian Unified Health System (SUS).

Вмешательства

• Препарат Subcutaneous Testosterone Implants
  Subcutaneous Testosterone Implants in Men With Symptomatic Hypogonadism

Первичные конечные точки

• Testosterone 200mg implants in hypogonadal men pharmacokinetics [Срок оценки: 180 days]

Вторичные конечные точки (12)

• Maximum Plasma Testosterone Concentration [Срок оценки: Up to 180 days]
• Time to Maximum Plasma Testosterone Concentration (Tmax) [Срок оценки: Up to 180 days]
• Plasma Testosterone Elimination Half-Life (T½) [Срок оценки: Up to 180 days]
• Average Plasma Testosterone Concentration (Cavg) [Срок оценки: Up to 180 days]
• Area Under the Plasma Concentration-Time Curve [Срок оценки: Up to 180 days]
• To evaluate the safety profile of testosterone implants. [Срок оценки: 180 days]
• Change in Serum Luteinizing Hormone (LH) Levels [Срок оценки: Up to 180 days]
• Evaluation of sexual outcomes [Срок оценки: 180 days]
• Evaluation of coagulation after testosterone implants [Срок оценки: 180 days]
• Change in Hypogonadal Symptoms Assessed by the Androgen Deficiency in the Aging Male Questionnaire [Срок оценки: Up to 180 days]
• To evaluate changes in quality of life in hypogonadal patients undergoing testosterone replacement therapy with implants [Срок оценки: 180 days]
• To evaluate the metabolic effects of testosterone implants using serum lipid profile [Срок оценки: 180 days]

Критерии участия

Критерии включения

• Absence of desire for future fertility.
• Two fasting total testosterone measurements ≤ 350 ng/dL obtained between 6:00 and 10:00 a.m.
• A positive ADAM questionnaire result (Participants with a prior diagnosis of testosterone deficiency established at this institution who are currently receiving testosterone replacement therapy and wish to participate in the study will be eligible for inclusion after completion of an appropriate washout period of the testosterone formulation in use.)

Критерии исключения

• Inability to complete or respond to study questionnaires.
• Body mass index (BMI) > 35 kg/m².
• Untreated depression, defined as a Beck Depression Inventory score > 20.
• Personal history of cancer.
• Suspicious findings on digital rectal examination or breast examination.
• Prostate-specific antigen (PSA) > 4 ng/mL.
• History of thrombosis.
• Known thrombophilia.
• Erythrocytosis.
• Polycythemia.
• Elevated liver enzymes (AST or ALT > 1.5 times the upper limit of normal).
• Untreated chronic disease.
• Heart failure classified as New York Heart Association (NYHA) class III or IV.
• History of cardiovascular disease within the previous 6 months.
• Substance use disorder or alcohol dependence.
• Use of antiandrogen medications (flutamide, bicalutamide, enzalutamide, apalutamide, spironolactone, cyproterone acetate, abiraterone, ketoconazole, dutasteride, finasteride).
• Use of estrogenic medications (estradiol, conjugated estrogens, progestogens).
• Use of anabolic androgenic steroids without medical indication.
• Untreated hypothyroidism.
• Known allergy or hypersensitivity to testosterone or any component of the implant (testosterone, stearic acid).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• Smith RP, Khanna A, Coward RM, Rajanahally S, Kovac JR, Gonzales MA, Lipshultz LI. Factors influencing patient decisions to initiate and discontinue subcutaneous testosterone pellets (Testopel) for treatment of hypogonadism. J Sex Med. 2013 Sep;10(9):2326-33. doi: 10.1111/jsm.12226. Epub 2013 Jul 16. PMID 23859250
• McMahon CG, Shusterman N, Cohen B. Pharmacokinetics, Clinical Efficacy, Safety Profile, and Patient-Reported Outcomes in Patients Receiving Subcutaneous Testosterone Pellets 900 mg for Treatment of Symptoms Associated With Androgen Deficiency. J Sex Med. 2017 Jul;14(7):883-890. doi: 10.1016/j.jsxm.2017.04.734. PMID 28673432
• Kaminetsky JC, Moclair B, Hemani M, Sand M. A phase IV prospective evaluation of the safety and efficacy of extended release testosterone pellets for the treatment of male hypogonadism. J Sex Med. 2011 Apr;8(4):1186-96. doi: 10.1111/j.1743-6109.2010.02196.x. Epub 2011 Jan 26. PMID 21269402
• Cavender RK, Fairall M. Subcutaneous testosterone pellet implant (Testopel) therapy for men with testosterone deficiency syndrome: a single-site retrospective safety analysis. J Sex Med. 2009 Nov;6(11):3177-92. doi: 10.1111/j.1743-6109.2009.01513.x. Epub 2009 Sep 29. PMID 19796052
• Kresch E, Lima TFN, Molina M, Deebel NA, Reddy R, Patel M, Loloi J, Carto C, Nackeeran S, Gonzalez DC, Ory J, Ramasamy R. Efficacy and safety outcomes of a compounded testosterone pellet versus a branded testosterone pellet in men with testosterone deficiency: a single-center, open-label, randomized trial. Sex Med. 2023 Mar 17;11(2):qfad007. doi: 10.1093/sexmed/qfad007. eCollection 2023 Apr. PMID 36936900
• McCullough A. A Review of Testosterone Pellets in the Treatment of Hypogonadism. Curr Sex Health Rep. 2014;6(4):265-269. doi: 10.1007/s11930-014-0033-7. PMID 25999802

Идентификаторы

NCT: NCT07500766 · 88009225.0.0000.0068

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗