Single-Dose Pharmacokinetics of Oral Testosterone Undecanoate With and Without Concomitant Inhibition of UGT2B17

Summary

This study will be performed in normal men whose endogenous testosterone production has been temporarily suppressed by the administration of a single dose of 120 mg of the oral GnRH antagonist Relugolix, which is approved for the treatment of prostate cancer, and can suppress endogenous testosterone biosynthesis for 48-72 hours after a single dose.

Timeline

Start

2024-06-01

Primary completion

2025-12-31

Completion

2025-12-31

Publications

• Background Katznelson L, Finkelstein JS, Schoenfeld DA, Rosenthal DI, Anderson EJ, Klibanski A. Increase in bone density and lean body mass during testosterone administration in men with acquired hypogonadism. J Clin Endocrinol Metab. 1996 Dec;81(12):4358-65. doi: 10.1210/jcem.81.12.8954042.
• Background Behre HM, Kliesch S, Leifke E, Link TM, Nieschlag E. Long-term effect of testosterone therapy on bone mineral density in hypogonadal men. J Clin Endocrinol Metab. 1997 Aug;82(8):2386-90. doi: 10.1210/jcem.82.8.4163.
• Background Bhasin S, Bremner WJ. Clinical review 85: Emerging issues in androgen replacement therapy. J Clin Endocrinol Metab. 1997 Jan;82(1):3-8. doi: 10.1210/jcem.82.1.3640. No abstract available.
• Background Plymate SR "Male Hypogonadism" in Principles and Practice of Endocrinology and Metabolism (3rd. Ed). Ed. Kenneth Becker, pp:1125-1150
• Background Wang C, Alexander G, Berman N, Salehian B, Davidson T, McDonald V, Steiner B, Hull L, Callegari C, Swerdloff RS. Testosterone replacement therapy improves mood in hypogonadal men--a clinical research center study. J Clin Endocrinol Metab. 1996 Oct;81(10):3578-83. doi: 10.1210/jcem.81.10.8855804.
• Background Wang C, Swerdloff RS. Testosterone Replacement Therapy in Hypogonadal Men. Endocrinol Metab Clin North Am. 2022 Mar;51(1):77-98. doi: 10.1016/j.ecl.2021.11.005. Epub 2022 Feb 8.
• Background Kelch RP, Jenner MR, Weinstein R, Kaplan SL, Grumbach MM. Estradiol and testosterone secretion by human, simian, and canine testes, in males with hypogonadism and in male pseudohermaphrodites with the feminizing testes syndrome. J Clin Invest. 1972 Apr;51(4):824-30. doi: 10.1172/JCI106877.
• Background Weinstein RL, Kelch RP, Jenner MR, Kaplan SL, Grumbach MM. Secretion of unconjugated androgens and estrogens by the normal and abnormal human testis before and after human chorionic gonadotropin. J Clin Invest. 1974 Jan;53(1):1-6. doi: 10.1172/JCI107526.
• Background Bagatell CJ, Bremner WJ. Androgens in men--uses and abuses. N Engl J Med. 1996 Mar 14;334(11):707-14. doi: 10.1056/NEJM199603143341107. No abstract available.
• Background Fossa SD, Opjordsmoen S, Haug E. Androgen replacement and quality of life in patients treated for bilateral testicular cancer. Eur J Cancer. 1999 Aug;35(8):1220-5. doi: 10.1016/s0959-8049(99)00123-9.
• Background Amory JK, Matsumoto AM. The therapeutic potential of testosterone patches. Expert Opin Investig Drugs. 1998 Dec;7(12):1977-85. doi: 10.1517/13543784.7.12.1977.
• Background Swerdloff RS, Wang C, Cunningham G, Dobs A, Iranmanesh A, Matsumoto AM, Snyder PJ, Weber T, Longstreth J, Berman N. Long-term pharmacokinetics of transdermal testosterone gel in hypogonadal men. J Clin Endocrinol Metab. 2000 Dec;85(12):4500-10. doi: 10.1210/jcem.85.12.7045.
• Background de Ronde W. Hyperandrogenism after transfer of topical testosterone gel: case report and review of published and unpublished studies. Hum Reprod. 2009 Feb;24(2):425-8. doi: 10.1093/humrep/den372. Epub 2008 Oct 23.
• Background Swerdloff RS, Dudley RE. A new oral testosterone undecanoate therapy comes of age for the treatment of hypogonadal men. Ther Adv Urol. 2020 Jun 30;12:1756287220937232. doi: 10.1177/1756287220937232. eCollection 2020 Jan-Dec.
• Background Bhatt DK, Basit A, Zhang H, Gaedigk A, Lee SB, Claw KG, Mehrotra A, Chaudhry AS, Pearce RE, Gaedigk R, Broeckel U, Thornton TA, Nickerson DA, Schuetz EG, Amory JK, Leeder JS, Prasad B. Hepatic Abundance and Activity of Androgen- and Drug-Metabolizing Enzyme UGT2B17 Are Associated with Genotype, Age, and Sex. Drug Metab Dispos. 2018 Jun;46(6):888-896. doi: 10.1124/dmd.118.080952. Epub 2018 Mar 30.
• Background Basit A, Amory JK, Mettu VS, Li CY, Heyward S, Jariwala PB, Redinbo MR, Prasad B. Relevance of Human Aldoketoreductases and Microbial beta-Glucuronidases in Testosterone Disposition. Drug Metab Dispos. 2023 Apr;51(4):427-435. doi: 10.1124/dmd.122.000975. Epub 2023 Jan 9.
• Background MacLean DB, Shi H, Faessel HM, Saad F. Medical Castration Using the Investigational Oral GnRH Antagonist TAK-385 (Relugolix): Phase 1 Study in Healthy Males. J Clin Endocrinol Metab. 2015 Dec;100(12):4579-87. doi: 10.1210/jc.2015-2770. Epub 2015 Oct 26.

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Indications