Clinical trial NCT06094283: First in Human Study Evaluating Single Ascending Oral Doses of YCT-529 in Healthy Males
Official title: Double-blind, Placebo Controlled, First in Human Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Ascending Oral Doses of YCT-529
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Male Contraception
Keywords: male
non-hormonal
male contraception
healthy males
sperm count reduction
sperm motility
impaired spermatogenesis
impaired motility
orally administered
vasectomy
vasectomized men
Lead sponsor: YourChoice Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2023-10-23
Enrollment: 16
Sex: MALE
Minimum age (years): 25
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: In each cohort, the first 2 sentinel subjects will be randomized in a 1:1 ratio to receive either YCT-529 or placebo. The remaining 6 subjects in each cohort will be enrolled in the dosing cohort such that 5 subjects will be randomized to receive YCT-529 and 1 subject will be randomized to receive placebo; therefore, a total of 6 subjects will be randomized to receive YCT-529 and 2 subjects will be randomized to receive placebo at each dose level.
Primary purpose: OTHER

Brief summary: A single ascending oral dose(s) study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of YCT-529 in healthy male subjects.

Detailed description: This is a Phase 1a, double-blind, placebo controlled, first in human study to evaluate the safety, tolerability, PK, and PD of YCT-529 in 2 cohorts of 8 subjects. Cohorts 1 and 2 will be dosed in the fasted state in Periods 1 and 2. Each cohort will receive two doses of study drug separated by a washout period. One cohort will then return for a third dose of study drug under fed conditions in Period 3 to study the effect of food on YCT-529.

Eligibility criteria: Inclusion Criteria:

1. Male subject in good health as confirmed by physical examination, medical history, and clinical laboratory tests of blood and urine at the time of Screening.
2. Subject must provide written informed consent.
3. Subject must be willing and able to communicate and participate in the whole study.
4. Subject is 25 to 60 years of age (inclusive).
5. Subject has been vasectomized for at least 6 months prior to enrolment
6. Subject has body mass index (BMI) 18.0 to 32.0 kg/m2.
7. Subject has no history of hormonal therapy uses in the 90 days prior to the first screening visit.
8. Subject agrees to use a condom during the study until the final return visit to ensure the safety of the study participants and their sexual partner(s)
9. Subjects will refrain from donating blood or plasma during the study.
10. Subjects will not use cannabis or any recreational drugs for at least 120 days before completing Screening and during the study.
11. In the opinion of the investigator, subject is able to adhere to the study requirements, restrictions, schedule of assessments, and requirements related to sperm sample collection and maintenance of the sexual activity diary.

Exclusion Criteria:

1. Men participating in another clinical study involving an investigational drug within the last 90 days prior to the first dosing or less than 5 elimination half-lives prior to first dosing, whichever is longer.
2. Clinically significant abnormal physical and/or laboratory findings at Screening
3. Abnormal serum chemistry values at screening or admission, that indicate liver or kidney dysfunction or that may be considered clinically significant, such as bilirubin of \>20 micro mol/L and ALT, AST, GGT and ALP above the upper limit of normal.
4. Evidence of renal impairment at screening, as indicated by an estimated eGFR of \<80 mL/min/1.73 m2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI; 2009) equation.
5. Use of androgens within 90 days before first screening visit.
6. Ongoing use of body building nutritional supplements.
7. Systolic blood pressure (BP) \>140 mmHg (\<45 years) or \>160 mmHg (≥45 years) and diastolic BP \>90 mmHg at screening or predose.
8. Clinically significant abnormal electrocardiogram (ECG) or a duration of corrected QT interval in ECG (QTc) interval of \>450 msec at screening or predose.
9. Known history of androgen deficiency due to hypothalamic-pituitary or testicular disease or multiple endocrine deficiencies.
10. Known history of significant cardiovascular, renal, hepatic (cholecystectomy is not permitted), or prostatic disease or significant psychiatric illness. Gilbert's syndrome is allowed (subject will be excluded if total bilirubin is ≥1.5 x ULN if known Gilbert's syndrome). If subject has elevations only in total bilirubin that are \>ULN and \<1.5xULN, fractionate bilirubin to identify possible undiagnosed Gilbert's syndrome (i.e., direct bilirubin \<35% of the total bilirubin).
11. Current or clinically relevant history of any psychiatric disorder or clinical assessment of significant suicidal risk or risk of self-injury as per the Investigator's judgement. This will be re-assessed at admission to Period 2 and Period 3 if applicable.
12. Serious adverse reaction or serious hypersensitivity to any drug or formulation excipients.
13. Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever is allowed unless it is active.
14. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) 1 and 2 antibody results at screening visit.
15. Known or suspected alcoholism or drug abuse within the last 2 years that may affect metabolism/transformation of steroid hormones or study treatment compliance.
16. Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator or delegate at screening.
17. Regular alcohol consumption in males \>14 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 units = 125 mL glass of wine, depending on type).
18. Current smokers and those who have smoked within the last 6 months. A confirmed breath carbon monoxide reading of greater than 10 ppm at screening or admission.
19. Confirmed positive drugs of abuse test result.
20. Subjects who are taking, or have taken, any prescribed or over-the-counter drug or vitamins/herbal remedies/supplements (other than up to 4 g of paracetamol per day in the 14 days before IMP administration). COVID-19 vaccines are accepted concomitant medications. Exceptions may apply, as determined by the investigator, if each of the following criteria are met: medication with a short half-life if the washout is such that no PD activity is expected by the time of dosing with IMP; and if the use of medication does not jeopardize the safety of the trial subject; and if the use of medication is not considered to interfere with the objectives of the study.
21. Male subjects with pregnant or lactating partners.
22. Subjects who are taking, or have taken, any prescribed or over-the-counter drug or vitamins/herbal remedies/supplements (other than up to 4 g of paracetamol per day in the 14 days before IMP administration). COVID-19 vaccines are accepted concomitant medications. Exceptions may apply, as determined by the investigator, if each of the following criteria are met: medication with a short half-life if the washout is such that no PD activity is expected by the time of dosing with IMP; and if the use of medication does not jeopardize the safety of the trial subject; and if the use of medication is not considered to interfere with the objectives of the study.
23. Any site staff member with delegated study responsibilities or a family member of a site staff member with delegated study responsibilities.
24. Any other medical condition that, in the opinion of the investigator, could alter the subject's well-being, the study conduct, or the interpretability of the results.

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Primary outcomes:
measure: The incidence and nature of any adverse events, dose-limiting adverse events and serious adverse adverse events.
timeFrame: Baseline to 43 days for subjects participating in Cohorts 1 and 2 participating in the 2 periods; Baseline to 10 weeks for Cohorts 1 and 2 that also complete the fed portion of the study; and Baseline to 16 weeks if waiting for other cohorts to finish
measure: Vital signs assessment (heart rate)
timeFrame: Baseline to Day 15
measure: Vital signs assessment (blood pressure)
timeFrame: Baseline to Day 15
measure: Vital signs assessment (oral temperature)
timeFrame: Baseline to Day 15
measure: 12-lead ECG assessment (heart rate)
timeFrame: Baseline to Day 15
measure: 12-lead ECG assessment (QT interval)
timeFrame: Baseline to Day 15
measure: 12-lead ECG assessment (QTcF Interval)
timeFrame: Baseline to Day 15
measure: 12-lead ECG assessment (PR Interval)
timeFrame: Baseline to Day 15
measure: 12-lead ECG assessment (QRS Duration)
timeFrame: Baseline to Day 15
measure: Clinical laboratory assessments (hematology blood sample tests)
timeFrame: Baseline to Day 15
measure: Clinical laboratory assessments (coagulation blood sample tests)
timeFrame: Baseline to Day 15
measure: Clinical laboratory assessments (clinical chemistry blood sample tests)
timeFrame: Baseline to Day 15
measure: Clinical laboratory assessments (urine sample tests)
timeFrame: Baseline to Day 15
Secondary outcomes:
measure: Plasma PK Parameter of YCT-529 (Area under the curve to Infinity [AUCinf])
timeFrame: Pre-dose to 336 hours after dosing
measure: Plasma PK Parameter of YCT-529 (Area under the curve to the last measured concentration [AUC0-t])
timeFrame: Pre-dose to 336 hours after dosing
measure: Plasma PK Parameter of YCT-529 (Area under the curve to 24 hours [AUC0--24])
timeFrame: Pre-dose to 336 hours after dosing
measure: Plasma PK Parameter of YCT-529 (Time to maximum concentration [Tmax])
timeFrame: Pre-dose to 336 hours after dosing
measure: Plasma PK Parameter of YCT-529 (Terminal elimination half life [T1/2])
timeFrame: Pre-dose to 336 hours after dosing
measure: Plasma PK Parameter of YCT-529 (Lag time [Tlag])
timeFrame: Pre-dose to 336 hours after dosing
measure: Plasma PK Parameter of YCT-529 (Volume of distribution [Vz/F])
timeFrame: Pre-dose to 336 hours after dosing
measure: Plasma PK Parameter of YCT-529 (oral clearance [CL/F])
timeFrame: Pre-dose to 336 hours after dosing
measure: Plasma PK Parameter of YCT-529 (maximum concentration [Cmax])
timeFrame: Pre-dose to 336 hours after dosing
measure: Pharmacodynamic parameter of YCT-529, including follicle-stimulating hormone
timeFrame: Pre-dose to 336 hours after dosing
measure: Pharmacodynamic parameter of YCT-529, including luteinizing hormone
timeFrame: Pre-dose to 336 hours after dosing
measure: Pharmacodynamic parameter of YCT-529, including testosterone
timeFrame: Pre-dose to 336 hours after dosing
measure: Pharmacodynamic parameter of YCT-529, including sex hormone binding globulin
timeFrame: Pre-dose to 336 hours after dosing
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: Quotient Sciences
state: East Midlands
Study officials:
affiliation: Quotient Sciences
name: Sharan Sidhu, MBChB
role: PRINCIPAL_INVESTIGATOR
References: