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
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 86
- 主要终点
- Number of Participants With treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
盲法说明
This is a double-blind study in which participants and investigators are blinded to treatment assignment.
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •• 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.
排除标准
- •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.
研究组 & 干预措施
ISM4808
Participants receive ISM4808 administered orally in single ascending dose and multiple ascending dose regimens.
干预措施: ISM4808 (Drug)
Placebo
Participants receive matching placebo administered orally in single ascending dose and multiple ascending dose regimens.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
时间窗: SAD/food-effect cohorts: From first dose up to Day 9; MAD cohorts: From first dose up to Day 18
A TEAE is an adverse event (AE) occurrence in a subject who received study drug whether or not considered related to the study product. Any adverse event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly or birth defect or any other situation according to medical or scientific judgment is categorized as SAE. The number of participants who experience at least one TEAE and SAE will be presented.
次要结局
- Terminal elimination half-life (t1/2) of ISM4808(SAD/Food-effect cohorts: Pre-dose through 72 hours post-dose)
- Terminal elimination half-life (t1/2) of ISM4808(MAD cohorts: Day 1 and Day 10)
- Time to Maximum Observed Plasma Concentration (Tmax) of ISM4808(SAD/Food-effect cohorts: Pre-dose through 72 hours post-dose)
- Time to Maximum Observed Plasma Concentration (Tmax) of ISM4808(MAD cohorts: Day 1 and Day 10)
- Maximum Observed Plasma Concentration (Cmax) of ISM4808(SAD/Food-effect cohorts: Pre-dose through 72 hours post-dose)
- Maximum Observed Plasma Concentration (Cmax) of ISM4808(MAD cohorts: Day 1 and Day 10)
- Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-t) of ISM4808(SAD/Food-effect cohorts: Pre-dose through 72 hours post-dose)
- Area Under the Plasma Concentration-Time Curve within a dosing interval (AUC0-tau) of ISM4808(MAD cohorts: Day 1 and Day 10)
- Average Steady-state Plasma Concentration (Cav) of ISM4808(MAD cohorts: Day 1 and Day 10)
- Amount Excreted into Urine (Ae)of ISM4808(MAD cohorts: 0-24 hours post dose on Day 10)
- Percentage of dose excreted in urine (Ae%) of ISM4808(MAD cohorts: 0-24 hours post dose on Day 10)