A Phase 1 Study of ISM4808 in Healthy Adult Subjects

A Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Oral ISM4808 in Healthy Adult Subjects in China

This is a Phase I, randomized, double-blind, placebo-controlled study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), food effect, and QTc effects of single and multiple ascending oral doses 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.