Open Label, Dose Escalation, Repeat Dose Study Evaluating YCT-529 in Healthy Males

Официальное название

Open Label Dose Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Repeated Daily Oral Dosing of YCT-529 for 28 Days, 90 Days or 180 Days in Healthy Men

Обзор

This is a Phase 1b/2a open-label, dose escalation 3 part-study, 28-day, 90-day or 180 day repeat dose study of YCT-529 in healthy males who have decided to have a vasectomy and are waiting for the procedure and for men who have decided not to father children in the future. The study is aimed at evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics and to assess sexual function and mood.

Подробное описание

This is a Phase 1b/2a, open label, 28-day, 90-day or 180-day repeat-dose escalation study of YCT-529 in healthy men to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics, and to assess sexual function and mood.

The study consists of 3 parts: a 28-day Phase 1b part (Part 1), a 90-day Phase 2a part (Part 2) and a 180-day Phase 2a part (Part 3). All participants will receive YCT-529.

In Part 1, 4 dosing cohorts and one optional 5th cohort with 4 participants each will be evaluated. In Part 2, up to 5 dosing cohorts and 2 optional cohorts with 4 participants each will be evaluated. Dose levels will be selected based on doses that were deemed safe and well tolerated upon 28-day administration in Part 1 and any previous Part 2 cohorts. Participants in Parts 1 and 2 may be replaced automatically if prior to any dosing. If a participant is required to be replaced post-dose, the replacement may beapproved at the discretion of Sponsor and PI with the objective of available data in at least 3 evaluable participants per cohort. In Part 3, 3 dosing cohorts and one optional 4th cohort with 10 participants each will receive doses within the range of doses that were deemed safe and well tolerated in Part 2. Participants who discontinue early may be replaced.

Вмешательства

• Препарат YCT-529
  In Part 1, 4 dosing cohorts and one optional 5th cohort with 4 participants each will be evaluated. In Part 2, up to 5 dosing cohorts and 2 optional cohorts with 4 participants each will be evaluated. Dose levels will be selected based on doses that were deemed safe and well tolerated upon 28-day administration in Part 1 and any previous Part 2 cohorts. In Part 3, 3 dosing cohorts and one optional 4th cohort with 10 participants each will receive doses within the range of doses that were deeme

Первичные конечные точки

• The incidence and nature of any adverse events, dose-limiting adverse events and serious adverse adverse events. [Срок оценки: For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.]
• Vital signs assessment (heart rate) [Срок оценки: For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.]
• Vital signs assessment (blood pressure) [Срок оценки: For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.]
• Vital signs assessment (oral temperature) [Срок оценки: For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.]
• 12-lead ECG assessment (heart rate) [Срок оценки: For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.]
• 12-lead ECG assessment (QT interval) [Срок оценки: For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.]
• 12-lead ECG assessment (QTcF Interval) [Срок оценки: For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.]
• 12-lead ECG assessment (PR Interval) [Срок оценки: For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.]
• 12-lead ECG assessment (QRS Duration) [Срок оценки: For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.]
• Clinical laboratory assessment- Hemoglobin Blood Sample Test [Срок оценки: For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.]

Вторичные конечные точки (12)

• Plasma PK Parameter of YCT-529 (Area under the curve to Infinity [AUCinf]) [Срок оценки: Pre-dose to 28 days post last dose in Part 1, and from pre-dose to 30 days post last dose in Parts 2 and 3.]
• Plasma PK Parameter of YCT-529 (Area under the curve to the last measured concentration [AUC0-t]) [Срок оценки: Pre-dose to 28 days post last dose in Part 1, and from pre-dose to 30 days post last dose in Parts 2 and 3.]
• Plasma PK Parameter of YCT-529 (Area under the curve to 24 hours [AUC0-24]) [Срок оценки: Pre-dose to 28 days post last dose in Part 1, and from pre-dose to 30 days post last dose in Parts 2 and 3.]
• Plasma PK Parameter of YCT-529 (Time to maximum concentration [Tmax]) [Срок оценки: Pre-dose to 28 days post last dose in Part 1, and from pre-dose to 30 days post last dose in Parts 2 and 3.]
• Plasma PK Parameter of YCT-529 (Terminal elimination half life [T1/2]) [Срок оценки: Pre-dose to 28 days post last dose in Part 1, and from pre-dose to 30 days post last dose in Parts 2 and 3.]
• Plasma PK Parameter of YCT-529 (Lag time [Tlag]) [Срок оценки: Pre-dose to 28 days post last dose in Part 1, and from pre-dose to 30 days post last dose in Parts 2 and 3.]
• Plasma PK Parameter of YCT-529 (Volume of distribution [Vz/F]) [Срок оценки: Pre-dose to 28 days post last dose in Part 1, and from pre-dose to 30 days post last dose in Parts 2 and 3.]
• Plasma PK Parameter of YCT-529 (oral clearance [CL/F]) [Срок оценки: Pre-dose to 28 days post last dose in Part 1, and from pre-dose to 30 days post last dose in Parts 2 and 3.]
• Plasma PK Parameter of YCT-529 (maximum concentration [Cmax]) [Срок оценки: Pre-dose to 28 days post last dose in Part 1, and from pre-dose to 30 days post last dose in Parts 2 and 3.]
• Pharmacodynamic parameter of YCT-529, including follicle-stimulating hormone [Срок оценки: Pre-dose to 28 days post last dose in Part 1, and from pre-dose to 30 days post last dose in Parts 2 and 3.]
• Pharmacodynamic parameter of YCT-529, including luteinizing hormone [Срок оценки: Pre-dose to 28 days post last dose in Part 1, and from pre-dose to 30 days post last dose in Parts 2 and 3.]
• Pharmacodynamic parameter of YCT-529, including estradiol [Срок оценки: Pre-dose to 28 days post last dose in Part 1, and from pre-dose to 30 days post last dose in Parts 2 and 3.]

Критерии участия

Критерии включения

• Participant in good health as confirmed by physical examination, medical history, and clinical laboratory tests.
• Participant must provide written informed consent.
• Participant must be willing and able to communicate and participate in the whole study.
• Participant is 28 to 70 years of age (inclusive) at the time of consent.
• Participant has decided to have a vasectomy and is waiting for the procedure or participant, in the opinion of the investigator, has made a firm decision not to father children in the future.
• Participant has a body mass index (BMI) 18.0 to 35.0 kg/m2.
• Participant has no history of hormonal therapy or 5-alpha reductase inhibitors use in the 90 days prior to the first screening visit.
• Participant with partner(s) of childbearing potential agrees to use a method of contraception that is highly effective with any partner (i.e., total abstinence or at a minimum, barrier method plus additional method of contraception) during the study until 28 days after the last dose (Day 56 \[Part 1\] or Day 118 \[Parts 2 and 3\]). Condom use is required during the course of the study with partner(s) of both childbearing and non-childbearing potential until Day 56 (Part 1) or Day 118 (Parts 2 and 3) to avoid potential secondary transmission of study drug and ensure the safety of the participants' sexual partner(s). Total abstinence from intercourse during the course of the study until Day 56 (Part 1) or Day 118 (Parts 2 and 3) is considered an acceptable form of contraception if this is in line with participant's preferred and/or usual lifestyle. Condom use is not required while practicing total abstinence.
• Participant will refrain from donating blood or plasma during the study.
• Participant will not use cannabis or any other recreational drugs for at least 30 days before the Screening visit and during the study. The marijuana/cannabis test can be positive at Screening but needs to be negative at admission (Day -1) for a volunteer to be eligible for inclusion in the study.
• Part 1: In the opinion of the investigator, participant 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. Parts 2 and 3: In the opinion of the investigator, participant is able to adhere to the study requirements, restrictions, schedule of assessments, and requirements related to semen sample collection and maintenance of the electronic dosing diary.
• Part 1: Participant providing at least 2 semen samples during the screening period with sperm parameters within at least the 5th percentile of the WHO range of normality (WHO, 2010 and WHO, 2021):

• 15 million sperm cells/mL
• 39 million sperm cells/total ejaculate
• 40% total motility
• 30% progressive motility Parts 2 and 3: Participant providing 3 semen samples during the screening period with ≥ 15 million sperm cells/mL (at least the 5th percentile of the WHO range of normality \[WHO, 2021\]).

Критерии исключения

• Men participating in another clinical study involving an investigational drug within the last 30 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 as determined by the PI, except for bilirubin >24 μmol/L and ALT, AST, GGT and ALP 2-fold above the upper limit of normal. Volunteers with known Gilbert's syndrome will be excluded if total bilirubin is ≥1.5 x ULN.
• Evidence of renal impairment at screening, as indicated by an estimated eGFR of <80 mL/min/1.73 m2 using the 2021 CKD-EPI Creatinine Equation (https://www.kidney.org/professionals/kdoqi/gfr\_calculator) .
• Use of androgens and selective androgen receptor modulators (SARMs) within 90 days before first screening visit.
• Volunteers with a body weight < 55 kg.
• Systolic blood pressure (BP) >140 mmHg (<45 years) or >160 mmHg (≥45 years) and diastolic BP >90 mmHg at screening and admission.
• Clinically significant abnormal electrocardiogram (ECG) or a duration of corrected QT interval using Bazett's and Fridericia's QT correction methods 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. Gilbert's syndrome is allowed (volunteer with known Gilbert's syndrome will be excluded if total bilirubin is ≥1.5 x ULN). If volunteer 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.
• 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. Seasonal allergies (e.g., hay fever) are allowed unless considered clinically significant by the investigator.
• 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.
• Volunteers who do not have suitable veins for multiple venipunctures/cannulation as assessed by the investigator or delegate at screening.
• Regular alcohol consumption in males >21 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.
• Current smokers who have consumed at least 5 cigarettes or equivalent amount of nicotine per week within the last 3 months prior to Screening.
• Confirmed positive drugs of abuse test result at Screening and admission and/or positive marijuana/cannabis test at admission (Day -1).
• Participants and volunteers 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 or up to 3.2 g of ibuprofen per day during the 14 days before IMP administration). COVID-19 vaccines are accepted concomitant medications. Other concomitant medications may be accepted at the discretion of both the PI and the Sponsor. 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 participant; and if the use of medication is not considered to interfere with the objectives of the study.
• Male volunteer with pregnant or lactating partner(s).
• Any site staff member with delegated study responsibilities or a family member of a site staff member with delegated study responsibilities.
• Any other medical condition that, in the opinion of the investigator, could alter the volunteer's well-being, the study conduct, or the interpretability of the results.

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Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Не применимо

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Другое

Центры проведения

Новая Зеландия · 1 центр

• New Zealand Clinical Research (NZCR) — Grafton

Идентификаторы

NCT: NCT06542237 · YCT-529-02

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗