This first-in-human study will evaluate ZE66-0205 in healthy adults. The main purpose is to assess the safety and tolerability of single oral doses and, if evaluated, two doses given on Day 1. The study will also assess how ZE66-0205 is absorbed, distributed, and eliminated from the body and how it affects MALT1 levels in blood cells. Participants will be assigned by chance to receive ZE66-0205 or placebo in sequential ascending-dose cohorts.
Inclusion Criteria:
Exclusion Criteria:
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Participants, the Sponsor, the Principal Investigator, and clinical study personnel involved in participant care or clinical evaluations will be blinded to treatment assignment. The randomisation statistician, designated unblinded pharmacy staff, unblinded study monitor, bioanalytical laboratory, and unblinded pharmacokineticist performing interim PK analyses will be unblinded. Data provided to the Safety Review Committee will be blinded.
Matching placebo. Two participants in each planned cohort will receive placebo capsules that match ZE66-0205 in appearance. Placebo will be administered orally under the same dosing and meal conditions as the corresponding active cohort. If twice-daily dosing is evaluated, placebo participants will receive a second dose approximately 12 hours after the first dose.
ZE66-0205 50 mg. Six participants will receive a single oral 50 mg dose on Day 1 under fasted conditions.
ZE66-0205 nominal 100 mg. Six participants will receive the SRC-confirmed oral dose on Day 1. The nominal dose is 100 mg; the actual dose may be adjusted based on emerging safety, PK, and PD data. Fed conditions or twice-daily dosing may be evaluated if selected by the SRC.
ZE66-0205 nominal 200 mg. Six participants will receive the SRC-confirmed oral dose on Day 1. The nominal dose is 200 mg; the actual dose may be adjusted based on emerging safety, PK, and PD data. Fed conditions or twice-daily dosing may be evaluated if selected by the SRC.
ZE66-0205 nominal 300 mg. Six participants will receive the SRC-confirmed oral dose on Day 1. The nominal dose is 300 mg; the actual dose may be adjusted based on emerging safety, PK, and PD data. Fed conditions or twice-daily dosing may be evaluated if selected by the SRC.
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