This is a single center, phase 1, randomized, double-blind, placebo-controlled sequential study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple ascending oral doses of ISM8969 in healthy adults and elderly participants and obese adult participants at risk of cardiovascular disease.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
100
Administration: Oral
Administration: Oral
Administration: Oral
Nucleus Network Pty Ltd.
Melbourne, Victoria, Australia
The incidence of Adverse Events (AEs) after single or multiple doses of ISM8969 tablets.
To evaluate the safety and tolerability of ISM8969.
Time frame: Up to 14 days after last dose.
Number of Participants with Clinical Laboratory Abnormalities, and Abnormalities in Vital Signs, Physical Examinations,12-lead ECG
Vital signs (blood pressure, heart rate, respiratory rate, and oral temperature), physical examinations, 12-lead ECG(heart rate , PR interval, QT interval, RR interval, QTcF and QRS),and clinical laboratory tests (hematology, biochemistry, coagulation and urinalysis, etc.)
Time frame: Up to 14 days after last dose.
C-SSRS Score(Type 1 to Type 5)
The C-SSRS(Columbia Suicidality Severity Rating Scale) is a suicidal ideation and behavior rating scale to evaluate suicide risk, higher C-SSRS scores mean a worse outcome.
Time frame: Up to 14 days after last dose.
Maximal observed plasma concentration (Cmax).
To characterize plasma PK of ISM8969 after the first dose and at steady state.
Time frame: Day 1 and Day 14 after dose.
Time when the maximal concentration is observed (Tmax).
To characterize plasma PK of ISM8969 after the first dose and at steady state.
Time frame: Day 1 and day 14 after dose.
Area under the concentration-time curve from time zero to the last observed concentration (AUC0-t).
To characterize plasma PK of ISM8969 after the first dose and at steady state.
Time frame: Day 3 and Day 17 after dose.
Area under the concentration-time curve from time zero to infinity (extrapolated)(AUC0-inf).
To characterize plasma PK of ISM8969 after single and multiple dose administration.
Time frame: Day 3 and Day 17 after dose.
Terminal elimination half-life(T½).
To characterize plasma PK of ISM8969 after single and multiple dose administration.
Time frame: Day 3 and Day 17 after dose.
Apparent clearance (CL/F).
To characterize plasma PK of ISM8969 after single and multiple dose administration.
Time frame: Day 1 and Day 14 after dose.
Apparent volume of distribution (V/F).
To characterize plasma PK of ISM8969 after single and multiple dose administration.
Time frame: Day 1 and day 14 after dose.
Maximal observed cerebrospinal fluid(CSF) concentration (Cmax,csf).
To characterize cerebrospinal fluid(CSF) PK of ISM8969 at steady state.
Time frame: Day 14 after dose.
Minimal observed concentration at steady-state (Cmin,ss).
1. To characterize plasma PK of ISM8969. 2. To characterize PK of ISM8969 in cerebrospinal fluid (CSF).
Time frame: Day 14 before the last dose.
Accumulation ratio (Day 14 : Day 1) (Racc).
To characterize the PK of ISM8969.
Time frame: Day 14 after dose.
Change from baseline in the concentration of blood high sensitivity C-reactive protein(hsCRP).
Concentration of hsCRP will be measured and reported.
Time frame: Day 14 after dose.
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