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

NCT06312761 | Not Yet Recruiting Phase 1

• 1 other identifier: Oral T-12
• Study Type: interventional
• Target: 10
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Hypogonadism, Male

Keywords

Oral Testosterone undecanoate; Hypogonadism; Curcumin; Testosterone replacement therapy

Outcome Measures

Primary Outcomes (6)

• average serum testosterone after dosing on day 2

  24 hour period (between dosing at beginning of day 2 and end of day 2)

• average serum testosterone after dosing on day 3

  24 hour period (between dosing at beginning of day 3 and end of day 3)

• Maximum concentration

  Cmax during 24 hour period (between dosing at beginning of day 2 and 3 and end of day 2 or day 3)

• time to maximum concentration

  T max during 24 hour period (between dosing at beginning of day 2 and 3 and end of day 2 or day 3)

• area-under-the curve

  24 hour period (between dosing at beginning of day 2 and 3 and end of day 2 or day 3)

• elimination phase half-life

  24 hour period (between dosing at beginning of day 2 and 3 and end of day 2 or day 3)

Study Arms (3)

Arm 1 Oral testosterone undecanoate without Curcumin

EXPERIMENTAL

Oral testosterone undecanoate 237 mg Day 2

Drug: Testosterone Undecanoate 237 MG Oral Capsule

Arm 2 Oral testosterone undecanoate with Curcumin

EXPERIMENTAL

Oral testosterone undecanoate 237 mg \& Curcumin 630 mg Day 3

Dietary Supplement: Curcumin; Drug: Testosterone Undecanoate 237 MG Oral Capsule

Relugolix 120 mg single dose

OTHER

All subjects will received Relugoliz on Day 1

Drug: Relugolix 120Mg Tab

Interventions

Relugolix 120Mg Tab DRUG

Relugolix 120 mg single dose - All subjects

Relugolix 120 mg single dose

Curcumin DIETARY_SUPPLEMENT

Curcumin 630 mg single dose

Arm 2 Oral testosterone undecanoate with Curcumin

Testosterone Undecanoate 237 MG Oral Capsule DRUG

Testosterone Undecanoate 237 MG Oral Capsule

Arm 1 Oral testosterone undecanoate without Curcumin; Arm 2 Oral testosterone undecanoate with Curcumin

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• \. healthy male between 18 and 55 years of age
• \. agrees to not participate in another drug research study for the duration of this study
• \. agrees to not donate blood during the study
• \. subject provided written (personally signed and dated) informed consent before completing any study-related procedures
• \. subject able and willing to comply with the protocol
• \. subject able and willing to not take medications other than the study drug for the duration of the study

You may not qualify if:

• \. subject has poor general health, determined by medical history or physical exam
• \. subject have an abnormal evaluation on screening exam (consisting of serum chemistry, hematology and baseline hormone levels)
• \. subject have a known history or current use of alcohol drug or steroid abuse and/or the use of more than 3 alcoholic beverages per day
• \. History of current testosterone use
• \. History of testicular disease or severe testicular trauma
• \. History of major psychiatric disorder
• \. subject participated in a hormonal drug study within the past month
• \. Subject or his partner(s) NOT willing to use an accepted method of contraception during the study
• \. History of Bleeding disorders or current use of anti-coagulants

Sponsors & Collaborators

• University of Washington: lead
• Washington State University: collaborator

Related Publications (17)

• 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.

  PMID: 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.

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• 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.

  PMID: 8989221 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.

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• 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.

  PMID: 35216722 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.

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• 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.

  PMID: 4271572 BACKGROUND

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  PMID: 8594431 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.

  PMID: 10615233 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.

  PMID: 15991940 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.

  PMID: 11134099 BACKGROUND

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  PMID: 18948313 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.

  PMID: 32655691 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.

  PMID: 29602798 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.

  PMID: 36623880 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.

  PMID: 26502357 BACKGROUND

MeSH Terms

Conditions

Eunuchism; Hypogonadism

Interventions

relugolix; Curcumin; testosterone undecanoate

Condition Hierarchy (Ancestors)

Gonadal Disorders; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Diarylheptanoids; Heptanes; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic

Study Officials

• John Amory, MD

  University of Washington

  PRINCIPAL INVESTIGATOR

Central Study Contacts

John Amory, MD

CONTACT

206-616-1727; jamory@uw.edu

Kathy Winter

CONTACT

206-616-0484; klwinter@uw.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, DOM - General Internal Medicine

Study Record Dates

• First Submitted: March 8, 2024
• First Posted: March 15, 2024
• Study Start: June 1, 2024
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: March 15, 2024

Record last verified: 2024-03