A Double-Blind, Placebo-Controlled, First-in-Human Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ZE50 0134 in Healthy Volunteers

INTERVENTION: Single‐ascending doses of ZE50‐0134 soft gelatin capsules are to be administered orally with noncarbonated room temperature water to healthy participants. Up to 5 planned dose levels of ZE50‐0134, 8 participants each, randomised (ZE50‐0134: placebo) as follows: Cohort 1: 100 mg Cohort 2: 200 mg Cohort 3: 400 mg Cohort 4: 800 mg Cohort 5: 1600 mg Participants will only be able to enrol in one dose cohort. The decision to escalate between dose levels will be based upon review of the blinded safety data and available pharmacokinetics (PK) data of each cohort by the Safety Review Committee (SRC). For each participant enrolled in Cohorts 1, 2, 3, 4 and 5, the confinement period will commence on Day ‐1, with dosing on Day 1 and discharge on Day 4. Participants will return to the clinic for their end of study (EoS) visit on Day 8. Adherence to Intervention will be managed via recording in appropriate drug accountability records. CONDITION: Cancer ‐ Leukaemia ‐ Chronic leukaemia Chronic lymphocytic leukemia (CLL) ; ; Chronic lymphocytic leukemia (CLL) PRIMARY OUTCOME: To assess the PK of ZE50‐0134 in plasma following administration of single oral doses in healthy adult volunteers. [Parameters to be examined include: Cmax, Tmax, AUC0‐last, AUC0‐24, AUC0‐inf, t1/2, Lambda z, CL/Fand Vz/F. Blood plasma samples will be collected as follows: Day 1 pre‐dose, 0.25hrs, 0.5hrs, 1hr, 2hrs, 4hrs, 6hrs, 8hrs and 12hrs post‐dose, Day 2 24hrs and 36hrs post‐dose, Day 3 48hrs post‐dose, Day 4 72hrs post‐dose and Day 8 168hrs post‐dose.] INCLUSION CRITERIA: 1. Adult males and females, 18 to 55 years of age (inclusive) at screening. 2. Body mass inde X(BMI) greater than or equal to 18.0 and less than or equal to 32.0 kg/m2, with a body weight (to 1 decimal place) greater than or equal to 50.0 kg at screening. 3. Medically healthy without clinically significant abnormalities (in the opinion of the Investigator) at the screening visit and prior to dosing at the timepoints indicated in the Schedule of Assessments (SoA), including: a. Physical examination without any clinically significant findings . b. Systolic blood pressure in the range of 90 mm Hg to 160 mm Hg; diastolic blood pressure in the range of 50 mm Hg to 95 mm Hg. c. Heart rate (HR) in the range of 45 to 100 bpm after 5 minutes in a supine or semi‐supine position d. Body temperature (tympanic or oral) in the range 35.5°C to 37.75°C (inclusive). e. No clinically significant findings in serum chemistry, haematology, coagulation and uri SECONDARY OUTCOME: To assess the safety and tolerability of single oral doses of ZE50‐0134 in healthy adult volunteers[Safety endpoints include: ; • Incidence, severity and relationship of adverse events (AEs)/serious AEs (SAEs) (including withdrawals due to AEs) ; • Change from baseline in body weight ; • Change from baseline in vital signs ; • Change from baseline in electrocardiogram (ECG) parameters ; • Change from baseline in clinical laboratory parameters (hematology, serum chemistry, coagulation and urinalysis) ; • Counts and percentages of lymphocyte sub‐populations (as defined below for pharmacodynamics (PD) parameters) will also be reviewed as part of safety monitoring) ; Adverse events ‐ will be graded using the most current version of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI‐CTCAE) (Version 5) and assessed continuously as they are reported or observed and reviewed daily for up to 8 days post‐dose, then on Day 28 and Day 56 post commencement of intervention (Safety follow‐up). ; ; Body Weight ‐ is measured using scales at Screening, Day ‐1 and Day 8 post commencement of intervention. ; ; Vital signs ‐ Blood pressure and heart rate is measured using sphygmomanometer, respiratory rate by manual breath count and temperature by thermometer. Measured from Screening, Day ‐1, Day 1 pre‐dose, 0.25hrs, 0.5hrs, 1hr, 2hrs, 4hrs, 6hrs, 8hrs and 12hrs post‐dose, Day 2 24hrs post‐dose, Day 3 48hrs post‐dose, Day 4 72hrs post‐dose and Day 8 168hrs post‐dose. ; ; Electrocardiogram (ECG) ‐ 12‐lead ECG recordings will be obtained in triplicate at screening, single recordings will be obtained from Screening, Day ‐1, pre‐dose Day 1, 1hr and 6hrs post‐dose, Day 2 24hrs post‐dose, Day 4 post‐dose and Day 8 post‐dose. ; ; Clinical laboratory evaluations (haematology, serum chemistry, coagulation and urinalysis) ‐ blood and urine samples will be collected from Screening, Day ‐1, Day 1 6hrs post‐dose, Day 2 24hrs post‐dose, Day 3 48hrs post‐dose, Day 8 post‐dose. On Day 28 and Day 56 (Safety follow‐up) post commencement of intervention blood samples for haematology parameters only will be collected.]