First-in-Human Single and Multiple Dose of HL-400

Официальное название

A Randomized, Double-blind, Placebo-controlled, Sequential Parallel Group, Single and Multiple Ascending Dose (SAD/MAD) Study in Healthy Subjects to Evaluate the Safety, Tolerability, Pharmacokinetics of HL-400 Following Oral Administration

Обзор

This is a randomized, double-blind, placebo-controlled, dose-escalation study in healthy subjects to evaluate the safety, tolerability, pharmacokinetics of HL-400 (a NLRP3 inhibitor) following oral single and multiple ascending dose administration.

Подробное описание

This is a randomized, double-blind, placebo-controlled, dose-escalation study in healthy subjects to evaluate the safety, tolerability, pharmacokinetics of HL-400 following oral single and multiple ascending dose administration.This study will consist of 3 parts, which are Part 1 (Single Ascending Dose), Part 2 (Multiple Ascending Dose) and Part3 (cerebrospinal fluid (CSF) Exposure).

Safety, pharmacokinetic parameters and relevant biomarkers will be assessed in the study.

Вмешательства

• Препарат HL-400
  Part 1:Experimental: Single oral dose of HL-400, Single ascending doses, sequential assignment group design; Part 2: Experimental: Multiple oral doses of HL-400, Multiple ascending doses, QD for 14 days, sequential assignment group design; Part 3: Experimental: Multiple oral doses of HL-400, QD for 5 days.
• Препарат Placebo
  Part 1: Placebo comparator: Single oral dose of placebo, single doses, matching placebo; Part 2: Placebo comparator: Multiple oral doses of placebo, multiple ascending doses, QD for 14 days, matching placebo.

Первичные конечные точки

• Number and percentage of participants with adverse events (AEs) [Срок оценки: From the time of taking first dose of study drug to 7 days after the last dose.]
• Number and percentage of adverse events (AEs) according to severity [Срок оценки: From the time of taking first dose of study drug to 7 days after the last dose.]
• Change in 12-lead electrocardiogram (ECG) parameters (PR Interval, QRS Complex, QT Interval, QTC Interval) from baseline [Срок оценки: From baseline to 7 days after the last dose.]
• Single Ascending Dose (SAD) Cohorts: Maximum observed plasma concentration (Cmax) of HL-400 [Срок оценки: From 0.5 hour to 72 hours post-dose.]
• Single Ascending Dose (SAD) Cohorts: Time to reach maximum observed plasma concentration (Tmax) of HL-400 [Срок оценки: From 0.5 hour to 72 hours post-dose.]
• Single Ascending Dose (SAD) Cohorts: Plasma decay half-life (t1/2) of HL-400 [Срок оценки: From 0.5 hour to 72 hours post-dose.]
• Single Ascending Dose (SAD) Cohorts: Area under the plasma concentration-time curve from time zero extrapolated to infinite time (AUCinf) of HL-400 [Срок оценки: From 0.5 hour to 72 hours post-dose.]
• Multiple Ascending Dose (MAD) Cohorts: Maximum observed plasma concentration (Cmax) of HL-400 [Срок оценки: From Day 1 pre-dose to 72 hours after the last dose.]
• Multiple Ascending Dose (MAD) Cohorts: Area under the plasma concentration-time curve from time zero extrapolated to infinite time (AUCinf) of HL-400 [Срок оценки: From Day 1 pre-dose to 72 hours after the last dose.]

Вторичные конечные точки (2)

• 1.The cerebrospinal fluid (CSF) cohort: Maximum observed concentration (Cmax) of HL-400 in the CSF [Срок оценки: From Day 1 pre-dose to 24 hours after the last dose]
• The cerebrospinal fluid (CSF) cohort: Area under the plasma concentration-time curve from time zero extrapolated to infinite time (AUCinf) of HL-400 in the CSF [Срок оценки: From Day 1 pre-dose to 24 hours after the last dose]

Критерии участия

Критерии включения

• Are capable of giving written informed consent and complying with study procedures, schedule, requirements, and restrictions.
• Are between the ages of 18 and 65 years, inclusive, at screening.
• Female subjects have a negative serum hCG pregnancy test result at screening andDay （-1）, agree to refrain from ova donation for at least 3 months after the last dose, and willingness to comply with protocol-specified contraceptive methods.
• Male subjects with female partners of reproductive potential must agree to practice abstinence or to use a condom (male subject) plus an additional barrier method (female partner) of contraception for the duration of the study and for at least 3 months after last dosing; must also agree to refrain from sperm donation for at least 3 months after the last dose.
• Considered healthy by the Investigator, based on subject's reported medical history, full physical examination, clinical laboratory tests, 12-lead ECG, and vital signs.
• Non-smoker for at least 6 months prior to screening.
• Body mass index (BMI) of 18.0 to 32.0 kg/m2 inclusive, except for MAD Cohort 3 subjects with a BMI of of 32.0 to 42.0 kg/m2 inclusive.

Критерии исключения

• Clinically significant history of gastrointestinal, cardiovascular, musculoskeletal, endocrine, hematologic, psychiatric, renal, hepatic, bronchopulmonary, neurologic, immunologic, lipid metabolism disorders, or drug hypersensitivity as determined by the Investigator.
• Pregnant (as determined by pregnancy test result) or breastfeeding women.
• History of chronic diarrhea, malabsorption, unexplained weight loss, food allergies or intolerance.
• Positive blood screen for human immunodeficiency virus (HIV 1/2), hepatitis B surface antigen (HBsAg), or hepatitis C antibody.
• A positive screen for alcohol or drugs of abuse at screening or Day -1.
• An unwillingness or inability to comply with food and beverage restrictions during study participation.
• Volunteers who have participated in any investigational drug or device study within past 3 months prior to dosing.
• Any condition or finding that in the Investigators opinion would put the subject or study conduct at risk if the subject were to participate in the study.

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

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Не применимо

Модель

Последовательный дизайн

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Pharmaron CPC, Inc. — Baltimore

Идентификаторы

NCT: NCT06997484 · HL-400-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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