This is a single-centre, randomized, double-blind, placebo-controlled Phase 1 study to assess safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of HL40626S tablets following single and multiple ascending oral doses to healthy adult participants aged 18-55 years.
In Part 1 (Single Ascending Dose, SAD), healthy participants are randomized to receive a single fasting oral dose of HL40626S tablets or matching placebo across five sequential ascending dose cohorts. Each cohort enrolls 8 participants. Sentinel dosing is implemented for every cohort to monitor initial safety before full cohort enrolment. In Part 2 (Multiple Ascending Dose, MAD), healthy participants are randomized to receive once-daily fasting oral doses of HL40626S tablets or matching placebo for 14 consecutive days across three sequential ascending dose cohorts. Each cohort enrolls 8 participants. All decisions to escalate to the next dose cohort were reviewed and approved by an independent Safety Review Committee (SRC) following complete data review of the preceding cohort.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
64
Oral study tablets administered in a dose-escalation design
Inactive oral placebo tablets matching the active drug dose-escalation scheme
Nucleus Network Pty Ltd
Melbourne, Australia
Parts 1 (SAD) and 2 (MAD): Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Assess incidence, severity, causality and clinical outcome of treatment-emergent adverse events (TEAEs) graded per CTCAE Version 6.0 to characterize the safety and tolerability of HL40626S in Part 1 (SAD) and Part 2 (MAD).
Time frame: From signed informed consent through Day 15 for SAD and Day 29 for MAD.
Parts 1 (SAD) and 2 (MAD): Incidence of serious adverse events (SAEs) [Safety and Tolerability]
Assess Incidence, severity, causality, and clinical outcome of serious adverse events (SAEs) graded per CTCAE Version 6.0 to characterize the safety and tolerability of HL40626S in Part 1 (SAD) and Part 2 (MAD).
Time frame: From signed informed consent through Day 15 for SAD and Day 29 for MAD.
Parts 1 (SAD) and 2 (MAD): Proportion of participants with clinically significant abnormal findings in physical examinations, vital signs, clinical laboratory tests, and 12-lead ECG assessments relative to baseline [Safety and Tolerability]
Abnormal findings from physical examinations, vital sign measurements, laboratory analyses and 12-lead ECG tracings are compared against each participant's baseline values to support the overall safety and tolerability assessment of HL40626S in Part 1 (SAD) and Part 2 (MAD).
Time frame: From signed informed consent through Day 15 for SAD and Day 29 for MAD.
Part 1 (SAD): Maximum observed plasma concentration (Cmax)
Calculate peak plasma HL40626S concentration following a single fasting oral administration
Time frame: Predose up to 5 days post single dose.
Part 1 (SAD): Time to maximum observed plasma concentration (Tmax)
Record the time point corresponding to the observed Cmax after single fasting oral administration.
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Time frame: Predose up to 5 days post single dose.
Part 1 (SAD): Area under the plasma concentration-time curve from time zero to last measurable concentration (AUClast)
Calculate AUClast via plasma concentration data collected over the sampling period following single-dose administration.
Time frame: Predose up to 5 days post single dose.
Part 1 (SAD): Area under the plasma concentration-time curve extrapolated to infinite time (AUCinf)
Assess the area under the plasma concentration-time curve extrapolated to infinite time (AUCinf) following single dose of HL40626S.
Time frame: Predose up to 5 days post single dose.
Part 1 (SAD): Terminal elimination rate constant (Kel)
Calculate terminal elimination rate constant following single dose of HL40626S tablets.
Time frame: Predose up to 5 days post single dose.