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

Phase 1

Not yet recruiting

• Conditions: Hypogonadism, Male
• Interventions: Drug: Relugolix 120Mg Tab; Dietary Supplement: Curcumin; Drug: Testosterone Undecanoate 237 MG Oral Capsule

• Registration Number: NCT06312761
• Lead Sponsor: University of Washington

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.

Detailed 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.

Study Timeline

• Status Verified: 2024-03
• Study First Submitted: 2024-03-08
• Study First Submitted QC: 2024-03-08
• Last Update Submitted: 2024-03-08
• Study First Posted: 2024-03-15
• Last Update Posted: 2024-03-15
• Study Start: 2024-06-01
• Primary Completion: 2025-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Male
• Target Recruitment: 10

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm 2 Oral testosterone undecanoate with Curcumin	Testosterone Undecanoate 237 MG Oral Capsule	Oral testosterone undecanoate 237 mg \& Curcumin 630 mg Day 3
Arm 1 Oral testosterone undecanoate without Curcumin	Testosterone Undecanoate 237 MG Oral Capsule	Oral testosterone undecanoate 237 mg Day 2
Relugolix 120 mg single dose	Relugolix 120Mg Tab	All subjects will received Relugoliz on Day 1
Arm 2 Oral testosterone undecanoate with Curcumin	Curcumin	Oral testosterone undecanoate 237 mg \& Curcumin 630 mg Day 3

Primary Outcome Measures

Name	Time	Method
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)