A Randomised, Double-Blind, Placebo-Controlled, First-in-Human Study of Orally Administered ZE75-0267 to Evaluate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Doses of ZE75-0267 in Healthy Volunteers

This is a double-blind, randomised, placebo-controlled study evaluating the safety, tolerability, and pharmacokinetics (PK) of ZE75-0267. The study will be conducted in 2 parts: a single ascending dose (SAD) part (Part A) at up to 6 dose levels and a multiple ascending dose (MAD) part (Part B) at up to 4 dose levels. Evaluation of dose levels will be conducted in a sequential fashion with lower dose levels evaluated first in the sequence. Participants will only be allowed to enroll in either Part A or B of the study. Part A: Each cohort will enroll 8 participants with 6 participants randomized to receive ZE75-0267 and 2 participants randomized to receive placebo on Day 1. There will be 6 cohorts and ZE75-0267 will be administered at the following dose levels: •SAD Cohort 1: 50 mg oral capsules (under fasted conditions) •SAD Cohort 2: 100 mg oral capsules (under fasted conditions) •SAD Cohort 3: 25 mg oral capsules (under fasted & fed conditions) •SAD Cohort 4: 25mg oral liquid (under fasted conditions) •SAD Cohort 5: TBC oral liquid (under fasted conditions) •SAD Cohort 6 (optional): TBC oral liquid (under fasted conditions) The dose level for SAD Cohorts 5-6 will be decided based on review of the safety data from the current and the previous cohort(s) and trailing PK data by the SRC. SAD Cohort 3 – food effect cohort: Single oral dose of ZE75-0267 or placebo administered on Day 1 under fasted conditions and another single oral dose administered on Day 15 under fed conditions (total of 2 doses). After an overnight fast of 10 hours, a high fat, high calorie meal will be consumed consisting of: 1. Two eggs fried in butter 2. Two rashers of bacon 3. Two slices of toast with 16 g butter per slice 4. 125 g of hash browns 5. 240 mL of full cream milk Part B: MAD Cohort 1 will enrol 8 participants each with 6 participants randomised to receive ZE75-0267 50 mg and 2 participants randomised to receive placebo once daily on Days 1 to 10 (total of 10 doses). MAD Cohort 2 will enrol 8 participants with all participants to receive ZE75-0267 25mg once daily on Days 1 to 10. MAD Cohort 3 and Cohort 4 will enrol 8 participants to receive ZE75-0267 or placebo oral liquid once daily for 10 or 14 days. Following review by the SRC of PK and PD data, it may be decided that MAD Cohort 3 and Cohort 4 participants be randomised to receive ZE75-0267 (6 participants) or placebo (2 participants) or all participants be assigned to receive active ZE75-0267. The dose will not exceed what has previously been studied. Study drug will be administered at the study site by trained study site personnel to ensure compliance.