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

Hypogonadism, Male Clinical Trial

— OralT12  

Official title:

Single-Dose Pharmacokinetics of Oral Testosterone Undecanoate With and Without Concomitant Inhibition of UGT2B17 With Oral Curcumin in Normal Men With Experimental Hypogonadism

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06312761
• Other study ID #: Oral T-12
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: June 1, 2024
• Est. completion date: December 31, 2025

Study information

• Verified date: March 2024
• Source: University of Washington
• Contact: John Amory, MD
• Phone: 206-616-1727
• Email: jamory[@]uw.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

The study will have three phases: a screening period, a 3-day drug exposure period, and a one-month recovery period (see Table 1, Experimental Design).

Screening Visit: At screening, study investigators will consent subjects, perform an interview and physical examination; blood samples for measurement of hormones (T,

DHT, Estradiol (E2), FSH and LH), routine hematology, chemistry and hepatic function and a DNA sample for UGT2B17 genotype will be obtained from the buccal mucosa and a spot urine specimen obtained for a testosterone glucuronide/androsterone glucuronide ratio (a marker of endogenous UGT2B17 activity). No drugs will be administered in the screening period. The screening visit should take approximately 60 minutes.

Day 1 (15-minute visit): Blood pressure and heart rate will be measured prior to the administration of Relugolix 120 mg orally on an empty stomach.

Day 2 (9 hour stay): Placement of IV and dosing of Testosterone Undecanoate 237 mg once with two ensures. The first dose of oral testosterone will be administered at 0900 (+/- 30 minutes) in the morning with two Ensures. After drug administration, subjects will have 10 ccs of blood drawn for the measurement of serum testosterone for the measurement of testosterone Predose, 0.5, 1, 1.5 2, 3, 4, 6, and 8 hours after the morning dose and will have the iv removed.

Day 3 (9 hour stay): Placement of IV and dosing of Testosterone Undecanoate 237 mg once with two Ensures and 630 mg of oral Curcumin. The second dose of oral testosterone will be administered at 0900 (+/- 30 minutes) in the morning. After drug administration, subjects will have 10 ccs of blood drawn for the measurement of serum testosterone for the measurement of testosterone Predose, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours after the morning dose and will have the iv removed.

Day 4 (15-minute visit): Subjects will come into the clinic at 0900 for a 24-hour blood draw and adverse effect assessment.

Day 28-42 (30-minute visit): Subjects will undergo a final assessment (physical examination, vitals and weight measurements and blood draw) on day 28-42. We will confirm at the follow-up visit that there has been recovery from Relugolix-induced hypogonadism (i.e., testosterone levels have returned to within 25% of baseline). If a subject has not recovered by this visit, he will be reassessed at 2-week intervals until recovery is documented. The total amount of blood drawn over the study protocol will not exceed 500 mL per subject.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 10
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• 1. healthy male between 18 and 55 years of age

• 2. agrees to not participate in another drug research study for the duration of this study

• 3. agrees to not donate blood during the study

• 4. subject provided written (personally signed and dated) informed consent before completing any study-related procedures

• 5. subject able and willing to comply with the protocol

• 6. subject able and willing to not take medications other than the study drug for the duration of the study

Exclusion Criteria:

• 1. subject has poor general health, determined by medical history or physical exam

• 2. subject have an abnormal evaluation on screening exam (consisting of serum chemistry, hematology and baseline hormone levels)

• 3. 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

• 4. History of current testosterone use

• 5. History of testicular disease or severe testicular trauma

• 6. History of major psychiatric disorder

• 7. subject participated in a hormonal drug study within the past month

• 8. Subject or his partner(s) NOT willing to use an accepted method of contraception during the study

• 9. History of Bleeding disorders or current use of anti-coagulants

Related Conditions & MeSH terms

• Hypogonadism
• Hypogonadism, Male

Intervention

Drug:
• Relugolix 120Mg Tab
Relugolix 120 mg single dose - All subjects

Dietary Supplement:
• Curcumin
Curcumin 630 mg single dose

Drug:
• Testosterone Undecanoate 237 MG Oral Capsule
Testosterone Undecanoate 237 MG Oral Capsule

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
University of Washington	Washington State University

References & Publications (17)

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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. — View Citation

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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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Plymate SR "Male Hypogonadism" in Principles and Practice of Endocrinology and Metabolism (3rd. Ed). Ed. Kenneth Becker, pp:1125-1150

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. Erratum In: Ther Adv Urol. 2021 Aug 20;13:17562872211036391. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	average serum testosterone after dosing on day 2		24 hour period (between dosing at beginning of day 2 and end of day 2)
Primary	average serum testosterone after dosing on day 3		24 hour period (between dosing at beginning of day 3 and end of day 3)
Primary	Maximum concentration		Cmax during 24 hour period (between dosing at beginning of day 2 and 3 and end of day 2 or day 3)
Primary	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)
Primary	area-under-the curve		24 hour period (between dosing at beginning of day 2 and 3 and end of day 2 or day 3)
Primary	elimination phase half-life		24 hour period (between dosing at beginning of day 2 and 3 and end of day 2 or day 3)