First in Human Study Evaluating Single Ascending Oral Doses of YCT-529 in Healthy Males

NCT06094283 | Completed Phase 1

• 2 other identifiers: YCT-529-011007466
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

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

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

Outcome Measures

Primary Outcomes (13)

• The incidence and nature of any adverse events, dose-limiting adverse events and serious adverse adverse events.

  Assessment of the number and type of adverse events, dose-limiting adverse events and serious adverse events following dosing.

  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

• Vital signs assessment (heart rate)

  Changes from pre-dose values (beats per minute)

  Baseline to Day 15

• Vital signs assessment (blood pressure)

  Changes from pre-dose values (mm hg)

  Baseline to Day 15

• Vital signs assessment (oral temperature)

  Changes from pre-dose values (temperature in celsius degrees)

  Baseline to Day 15

• 12-lead ECG assessment (heart rate)

  Changes from pre-dose values (beats per minute)

  Baseline to Day 15

• 12-lead ECG assessment (QT interval)

  Changes from pre-dose values for QT internal length (msec)

  Baseline to Day 15

• 12-lead ECG assessment (QTcF Interval)

  Changes from pre-dose values for QTcF interval length (msec)

  Baseline to Day 15

• 12-lead ECG assessment (PR Interval)

  Changes from pre-dose values for PR interval length (msec)

  Baseline to Day 15

• 12-lead ECG assessment (QRS Duration)

  Changes from pre-dose values for QRS duration (msec)

  Baseline to Day 15

• Clinical laboratory assessments (hematology blood sample tests)

  Changes from pre-dose values (Tests: Hemoglobin, Hematocrit, packed cell volume, Red blood cell, erythrocyte count, mean corpuscular volume, mean corpuscular hemoglobin, Mean corpuscular hemoglobin concentration, Platelet count, White blood cell, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils

  Baseline to Day 15

• Clinical laboratory assessments (coagulation blood sample tests)

  Changes from pre-dose values (Tests: Prothrombin time, Activated partial thromboplastin time (APTT), Fibrinogen)

  Baseline to Day 15

• Clinical laboratory assessments (clinical chemistry blood sample tests)

  Changes from pre-dose values (Tests: Sodium, Potassium, Chloride, Bicarbonate, Urea, Creatinine, Bilirubin (total), Bilirubin (direct; only if total is elevated), Alkaline phosphatase, Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Lactate dehydrogenase (LDH), Creatine kinase (CK), Gamma glutamyl transferase (GGT), Protein (Total), Albumin, Calcium, Glucose (fasting), Glucose,Triglycerides (fasting) Cholesterol (total; fasting)

  Baseline to Day 15

• Clinical laboratory assessments (urine sample tests)

  Changes from pre-dose values (Bilirubin, Urobilinogen, Ketones, Glucose, Protein, Blood, Nitrites, pH, Specific gravity, Leukocytes)

  Baseline to Day 15

Secondary Outcomes (13)

• Plasma PK Parameter of YCT-529 (Area under the curve to Infinity [AUCinf])

  Pre-dose to 336 hours after dosing

• Plasma PK Parameter of YCT-529 (Area under the curve to the last measured concentration [AUC0-t])

  Pre-dose to 336 hours after dosing

• Plasma PK Parameter of YCT-529 (Area under the curve to 24 hours [AUC0--24])

  Pre-dose to 336 hours after dosing

• Plasma PK Parameter of YCT-529 (Time to maximum concentration [Tmax])

  Pre-dose to 336 hours after dosing

• Plasma PK Parameter of YCT-529 (Terminal elimination half life [T1/2])

  Pre-dose to 336 hours after dosing

Study Arms (2)

YCT-529

ACTIVE COMPARATOR

Oral single ascending dose(s)

Drug: YCT-529

Placebo

PLACEBO COMPARATOR

Placebo for YCT-529 Capsule

Drug: YCT-529 Placebo

Interventions

YCT-529 DRUG

Single oral dose (planned doses of 10, 30, 90 and 200 mg; dose levels will not exceed 250 mg

YCT-529

YCT-529 Placebo DRUG

YCT-529 Placebo

Placebo

Eligibility Criteria

• Age: 25 Years - 60 Years
• Gender Eligibility Details: Sex assigned at birth is required to be "male"
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• Subject must provide written informed consent.
• Subject must be willing and able to communicate and participate in the whole study.
• Subject is 25 to 60 years of age (inclusive).
• Subject has been vasectomized for at least 6 months prior to enrolment
• Subject has body mass index (BMI) 18.0 to 32.0 kg/m2.
• Subject has no history of hormonal therapy uses in the 90 days prior to the first screening visit.
• 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)
• Subjects will refrain from donating blood or plasma during the study.
• Subjects will not use cannabis or any recreational drugs for at least 120 days before completing Screening and during the study.
• 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.

You may not qualify if:

• 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.
• Clinically significant abnormal physical and/or laboratory findings at Screening
• 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.
• 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.
• Use of androgens within 90 days before first screening visit.
• Ongoing use of body building nutritional supplements.
• Systolic blood pressure (BP) \>140 mmHg (\<45 years) or \>160 mmHg (≥45 years) and diastolic BP \>90 mmHg at screening or predose.
• Clinically significant abnormal electrocardiogram (ECG) or a duration of corrected QT interval in ECG (QTc) interval of \>450 msec at screening or predose.
• Known history of androgen deficiency due to hypothalamic-pituitary or testicular disease or multiple endocrine deficiencies.
• 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).
• 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.
• Serious adverse reaction or serious hypersensitivity to any drug or formulation excipients.
• Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever is allowed unless it is active.
• 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.
• Known or suspected alcoholism or drug abuse within the last 2 years that may affect metabolism/transformation of steroid hormones or study treatment compliance.

Sponsors & Collaborators

• YourChoice Therapeutics, Inc.: lead

Study Sites (1)

Quotient Sciences

Nottingham, East Midlands, NG11 6JS, United Kingdom

Location

Related Publications (1)

• Mannowetz N, McCallum SW, Sidhu S, Mena KH, Ruby EP, Castro-Santamaria R, Dodds E, Henderson D, Whitaker G, Wright H, Beaudoin S, Bakshi A. Safety and pharmacokinetics of the non-hormonal male contraceptive YCT-529. Commun Med (Lond). 2025 Jul 22;5(1):279. doi: 10.1038/s43856-025-01004-4.

  PMID: 40696162 DERIVED

Study Officials

• Sharan Sidhu, MBChB

  Quotient Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blind, placebo controlled
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: May 3, 2023
• First Posted: October 23, 2023
• Study Start: December 20, 2023
• Primary Completion: June 18, 2024
• Study Completion: June 18, 2024
• Last Updated: October 2, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)