A Phase 1 Study of ISM4808 in Healthy Adult Subjects

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат ISM4808
  ISM4808 administered orally as capsules in single ascending dose and multiple ascending dose regimens, with flexible dosing schedules based on emerging safety and pharmacokinetic data.
• Препарат Placebo
  Matching placebo administered orally under the same conditions as ISM4808.

Первичные конечные точки

• Number of Participants With treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) [Срок оценки: SAD/food-effect cohorts: From first dose up to Day 9; MAD cohorts: From first dose up to Day 18]

Вторичные конечные точки (11)

• Terminal elimination half-life (t1/2) of ISM4808 [Срок оценки: SAD/Food-effect cohorts: Pre-dose through 72 hours post-dose]
• Terminal elimination half-life (t1/2) of ISM4808 [Срок оценки: MAD cohorts: Day 1 and Day 10]
• Time to Maximum Observed Plasma Concentration (Tmax) of ISM4808 [Срок оценки: SAD/Food-effect cohorts: Pre-dose through 72 hours post-dose]
• Time to Maximum Observed Plasma Concentration (Tmax) of ISM4808 [Срок оценки: MAD cohorts: Day 1 and Day 10]
• Maximum Observed Plasma Concentration (Cmax) of ISM4808 [Срок оценки: SAD/Food-effect cohorts: Pre-dose through 72 hours post-dose]
• Maximum Observed Plasma Concentration (Cmax) of ISM4808 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: MAD cohorts: Day 1 and Day 10]
• Average Steady-state Plasma Concentration (Cav) of ISM4808 [Срок оценки: MAD cohorts: Day 1 and Day 10]
• Amount Excreted into Urine (Ae)of ISM4808 [Срок оценки: MAD cohorts: 0-24 hours post dose on Day 10]
• Percentage of dose excreted in urine (Ae%) of ISM4808 [Срок оценки: MAD cohorts: 0-24 hours post dose on Day 10]

Критерии участия

Критерии включения

• • 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Фундаментальное исследование

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07415304 · ISM4808-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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