A Phase 1 Study of ISM4808 in Healthy Adult Subjects

The study consists of two parts, Part 1 includes single ascending dose (SAD) and food effect (FE) assessments, FE assessments will be conducted in a selected dose cohort from the single ascending dose phase, using the same subjects after an appropriate washout period, AND Part 2 includes multiple ascending dose (MAD) evaluations. Safety, PK, PD, and concentration-QTc relationship will be assessed across dose levels.

Dose escalation decisions will be based on the review of available safety, tolerability, and pharmacokinetic data by a Safety Monitoring Committee.

Inclusion criteria

• • Able and willing to provide written informed consent and comply with all study procedures.

• Healthy male or female adults aged 18 to 55 years at the time of informed consent.
• Body mass index (BMI) 19-26 kg/m²; body weight ≥50 kg (males) and ≥45 kg (females).
• Medically healthy with no clinically significant abnormalities in medical history, physical examination, vital signs, laboratory tests, or 12-lead ECG, as determined by the investigator.
• Women of childbearing potential and male subjects with partners of childbearing potential must agree to use effective contraception from screening through 3 months after the last dose of investigational product.

Exclusion criteria

• History or presence of any clinically significant disease (including cardiovascular, neurological, psychiatric, gastrointestinal, hepatic, renal, hematologic, endocrine, or immune disorders) that may interfere with study participation or data interpretation.
• Personal or family history of clinically significant cardiac disease, including QT prolongation, torsades de pointes, myocardial infarction, heart failure, or sudden cardiac death.
• Use of medications known to prolong QT/QTc interval or treatment for clinically significant cardiac conditions.
• Screening 12-lead ECG abnormalities, including QTcF >450 ms (males) or >470 ms (females), PR interval >210 ms, QRS duration >110 ms, clinically significant arrhythmias, or uncontrolled hypertension.
• Participation in another interventional clinical trial or receipt of any investigational drug within 3 months prior to first dosing.
• Blood donation or significant blood loss (≥400 mL) within 3 months prior to first dosing.
• Pregnant or breastfeeding women, or positive pregnancy test at screening or prior to dosing.
• Positive tests for HBsAg, HCV antibody, HIV antibody, or syphilis.
• History of drug or alcohol abuse, positive drug screen, or inability to abstain from alcohol, nicotine, or prohibited substances during the study.
• Use of prescription or non-prescription medications, herbal products, supplements, or vaccines within 28 days prior to dosing, unless approved by the investigator.
• Any condition that, in the opinion of the investigator, would make the subject unsuitable for participation in the study.