An Exploratory Randomized, Double-Blind, Placebo-Controlled, First-in-Human Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Doses of ZE63-0302 in Healthy Volunteers

This is a an exploratory Phase I, single and multiple dose escalation clinical trial conducted in healthy volunteers. The safety, tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of ZE63-0302 following oral administration in healthy volunteers will be evaluated using a randomised, double-blind, placebo-controlled trial design. A total of up to 88 healthy volunteers are planned to be enrolled in up to 7 Single Ascending Dose (SAD) cohorts and up to 4 Multiple Ascending Dose (MAD) cohorts . Eligible participants will be randomised to receive a single or multiple dose of ZE63-0302 or placebo administered as an oral capsule on under fasted or fed conditions depending on cohort. Part A (SAD): ZE63-0302 will be evaluated across 7 SAD cohorts with one cohort to additionally receive 200 mg itraconazole on Day -4 and Days 3 - 8 at the following dose levels: • Cohort 1: 20 mg, fasted • Cohort 2: 100 mg, fasted • Cohort 3: 300 mg, fasted • Cohort 4: 600 mg, fasted • Cohort 5: 300 mg, fed • Cohort 6: 600 mg, fasted plus itraconazole • Cohort 7: 600 mg, fed The decision to escalate between dose levels will be based upon review of the safety data and available PK data of each cohort by the Safety Review Committee (SRC). Part B (MAD): ZE63-0302 or placebo is to be evaluated across up to 4 MAD cohorts. MAD cohort dosing will be either a single oral dose once or twice daily for 7 days or twice daily from Day 1 - 2 then escalated twice daily from Day 3 - 7 under fasted / fed conditions depending on cohort at the following dose levels: • Cohort 1: 600 mg once daily (7 days), fasted or fed • Cohort 2: up to 600 mg twice daily (7 days), fasted or fed • Cohort 3: 300 mg twice daily, fasted from Day 1 – 2, escalated to 600 mg twice daily, fasted from Day 3 – 7. Last dose will be on the morning of Day 7. • Cohort 4: 300 mg twice daily, fed (normal diet) from Day 1- 2, escalated to 600 mg twice daily, fed from Day 3 – 7. The decision to escalate between dose levels will be based upon review of the safety data and available PK data of each cohort by the Safety Review Committee (SRC). Participants in the fed cohorts will be provided with a high-fat, high-caloric meal after a 10 hour fast overnight, consisting of the following: two eggs fried in butter, two rashers of bacon, two slices of toast with 16 g butter per slice, 125 g of hash brown potatoes and 240 mls of whole milk. ZE63-0302 or placebo will be administered following the consumption of the meal. Adherence to the intervention will be done via supervised drug administration.