The oral TRT study plans to enroll 20 male patients aged 18 to 49 years who meet the American Urological Association’s criteria for hypogonadism and who have not previously used TRT.
A pilot study has been initiated to explore the effect of the oral testosterone replacement therapy (TRT), testosterone undecanoate (Kyzatrex), on spermatogenesis in males with hypogonadism, announced Marius Pharmaceuticals, the developer of the therapy, in a news release.1
According to the release, current data on TRT has shown decreases in spermatogenesis, but the studies are based on traditional routes of administration such as injections, patches, gels, implantable pallets, etc. The current study would be the first to explore the effect of oral TRT on spermatogenesis.
"Historically, testosterone products have been known to impair sperm production. Thus, many young hypogonadal men planning to achieve a pregnancy are unable to use testosterone due to an increased risk of suppressing their sperm production. Identifying testosterone therapy that could potentially not suppress sperm production would be a significant advancement in the way we treat these hypogonadal men,” said principal investigator Mohit Khera, MD, MBA, MPH, in the news release.1 Khera is a professor of urology at Baylor College of Medicine in Houston, Texas.
The oral TRT study plans to enroll 20 male patients aged 18 to 49 years who meet the American Urological Association’s criteria for hypogonadism and who have not previously used TRT. Each patient will receive 200 mg to 400 mg of testosterone undecanoate twice daily for 3 months.
The investigators will conduct 2 semen analyses for each patient at baseline, 1 month, and 3 months to assess changes in sperm count. They will also measure testosterone, hormones, lipids, and hematocrit levels at these time points via blood draws. A blood draw will also be conducted at 2 weeks following therapy initiation to support drug titration to reach therapeutic levels.
Further, patients will be asked to complete International Index of Erectile Function, Patient Health Questionnaire-9, and 36-Item Short Form Health Survey questionnaires at baseline and at the conclusion of the study to assess changes in symptoms of low testosterone.
"We are eager to begin this new pilot study, as finding an option of TRT that does not reduce fertility in men would be a significant milestone in the field of andrology and society as a whole," said Andrew Sun, MD, director at the center for men's health at Urology Partners of North Texas and the chief medical advisor for Marius Pharmaceuticals, in the news release.1 "Too many men are suffering in silence from the effects of testosterone deficiency, and the results from this study could help us better understand the effects of oral TRT on spermatogenesis, which might potentially benefit a subset of men; those who are looking to start a family while still treating their low T."
Testosterone undecanoate was approved by the FDA in August 2022 at the dose levels 100 mg, 150 mg, and 200 mg for the treatment of patients with conditions associated with hypogonadism.2
The approval was based on findings from the multicenter, open-label, phase 3 MRS-TU-2019EXT (NCT03198728) study, which evaluated the safety and efficacy of the therapy in men aged 18 to 65. Each patient had hypogonadism, as defined by low serum testosterone levels of 281 ng/dL or below, as well as at least 1 sign or symptom of testosterone deficiency.
Of the total patient population (n = 155), 139 patients were eligible for the efficacy analysis. Overall, the study met its primary end point with 88% of patients achieving a mean plasma total testosterone concentration over 24 hours within the normal range (defined as 222 ng/dL to 800 ng/dL) on the final pharmacokinetic visit on day 90 of the study.
Further exploratory end points demonstrated patient-reported improvements in quality of life, energy and fatigue, erectile function, intercourse satisfaction, and positive mood following treatment with testosterone undecanoate.
Regarding safety, the most commonly reported adverse event was increased blood pressure, which was observed in 2.6% of patients.
1. Marius Pharmaceuticals announces pilot study exploring the effect of its oral testosterone therapy KYZATRAX (CIII testosterone undecanoate capsules), on male fertility. News release. Marius Pharmaceuticals. January 9, 2024. Accessed January 10, 2024. https://www.prnewswire.com/news-releases/marius-pharmaceuticals-announces-pilot-study-exploring-the-effect-of-its-oral-testosterone-therapy-kyzatrex-ciii-testosterone-undecanoate-capsules-on-male-fertility-302030019.html
2. Marius Pharmaceuticals receives FDA approval of KYSZTREX, an oral testosterone replacement therapy. News release. Marius Pharmaceuticals. August 2, 2022. Accessed January 10, 2024. https://www.biospace.com/article/releases/marius-pharmaceuticals-receives-fda-approval-of-kyzatrex-an-oral-testosterone-replacement-therapy/