A Phase 1 MAD Study to Evaluate the Safety and Tolerability of LY03020

Официальное название

A Randomized, Double-Blind, Placebo-Controlled, Dose- Ascending Phase I Clinical Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Multiple Oral Doses of LPM787000048 Maleate Extended-Release Tablets (LY03020) in Chinese Adult Healthy Subjects and/or Subjects With Stable Schizophrenia

Обзор

This is a randomized, double-blind, placebo-controlled, ascending multiple oral dose study to assess the safety, tolerability, and pharmacokinetics of LY03020 in Chinese healthy adult subjects and/or subjects with stable schizophrenia.

Вмешательства

• Препарат LY03020
  administered orally
• Препарат Placebo
  administered orally

Первичные конечные точки

• Number of participants with adverse events (AEs) and serious adverse events (SAEs). [Срок оценки: up to Day 11]

Вторичные конечные точки (12)

• Number of participants with clinical laboratory assessment abnormalities. [Срок оценки: up to Day 11]
• Change from Baseline in Positive and Negative Syndrome Scale (PANSS) at Day 11 of subjects with stable schizophrenia [Срок оценки: up to Day 11]
• Change from Baseline in Columbia - Suicide Severity Rating Scale (C-SSRS) at Day 11 of subjects with stable schizophrenia [Срок оценки: up to Day 11]
• Change from Baseline in Barnes Akathisia Rating Scale (BARS) at Day4 and Day 11 of subjects with stable schizophrenia [Срок оценки: up to Day 11]
• Change from Baseline in Simpson-Angus Scale (SAS) at Day4 and Day 11 of subjects with stable schizophrenia [Срок оценки: up to Day 11]
• Maximum observed concentration at steady state (Cmax,ss) of LPM787000048 in plasma [Срок оценки: up to Day 11]
• Minimum observed concentration at steady state (Cmin,ss) of LPM787000048 in plasma [Срок оценки: up to Day 11]
• Area under the concentration- time curve during the dosing interval at steady state (AUC0-τ,ss) of LPM787000048 in plasma [Срок оценки: up to Day 11]
• Area under the concentration-time curve from time zero extrapolated to infinity at steady state (AUC0-∞,ss) of LPM787000048 in plasma [Срок оценки: up to Day 11]
• Time to maximum observed concentration at steady (Tmax,ss) state of LPM787000048 in plasma [Срок оценки: up to Day 11]
• Apparent terminal elimination half-life (t1/2) of LPM787000048 in plasma [Срок оценки: up to Day 11]
• AUC Accumulation Ratio (Ra(AUC)) of LPM787000048 in plasma [Срок оценки: up to Day 11]

Критерии участия

Критерии включения

Healthy Subjects

• Subjects sign informed consent voluntarily.
• Male or female aged 18 to 45 years.
• Body weight ≥ 50.0 kg for male and ≥ 45.0 kg for female, and body mass index (BMI) between 18.5 and 26.0 kg/m2 Subjects with Stable Schizophrenia
• Subjects themselves and / or their guardians sign informed consent voluntarily.
• Male or female aged 18 to 60 years.
• Body weight ≥ 50.0 kg for male and ≥ 45.0 kg for female, and body mass index (BMI) between 18.5 and 32.0 kg/m2.
• Subject must meet the DSM-V criteria for a primary diagnosis of schizophrenia. Subject must have a PANSS total score ≤ 80 and CGI-S score ≤ 4 at screening. The condition is stable from 1 month before signing informed consent to baseline.

Критерии исключения

Healthy Subjects

• Subjects have any clinically significant medical condition or chronic disease.
• Subjects have used any of nonprescription drugs within 7 days or prescription drugs within 28 days prior to administration.
• Subjects experienced a history of keratopathy, fundus disease, increased intraocular pressure, or angle-closure glaucoma. Subjects have any abnormal and clinically significant test for ophthalmic examination during screening.
• Subjects with a history of orthostatic hypotension or syncope.
• Subjects with condition that may interfere with the drug absorption, distribution, metabolism and excretion significantly.
• Subjects had a history of surgery within 3 months prior to administration, or had not recovered, or have a surgical plan during the study.
• Subjects have any clinically significant abnormal vital signs, laboratory values, and ECGs.
• Subjects have a history of allergic diseases, or allergic to any substance contained in the formulation
• Subjects have a positive test for HBsAg, HCV-Ab, HIV-Ab, or syphilis antibody. Subjects with Stable Schizophrenia
• According to the DSM-5, there were other mental disorders except schizophrenia within 6 months before screening period.
• Assessed by the investigator as having treatment-resistant schizophrenia; past or current diagnosis of neuroleptic malignant syndrome (NMS); anticipated need for antipsychotic regimen modifications during the study period;
• History of suicide attempts (including actual attempts, interrupted attempts, or failed attempts) or suicidal ideation within the past 6 months, defined as affirmative responses ("yes") to question 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) at screening/baseline;
• Subjects have used monoamine oxidase inhibitors (MAOI) within 28 days or any dietary supplements/traditional Chinese herbal products within 7 days prior to first dosing.
• Glycated hemoglobin (HbA1c) ≥7% at screening/baseline.
• Congenital long QT syndrome; uncontrolled or severe cardiovascular disease, including NYHA class II or higher congestive heart failure, unstable angina, myocardial infarction within 6 months prior to screening, or presence of treatment-requiring severe arrhythmias (e.g., sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes) at screening; resting heart rate <50 beats per minute (bpm) at screening/baseline; or QTc >450 ms (male) / QTc >460 ms (female) based on Fridericia's formula-corrected measurements at screening/baseline.
• Subjects experienced a history of keratopathy, fundus disease, increased intraocular pressure, or angle-closure glaucoma. Subjects have any abnormal and clinically significant test for ophthalmic examination during screening.
• Subjects with a history of orthostatic hypotension or syncope.

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

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Beijing AnDing Hospital Capital Medical University — Пекин

Идентификаторы

NCT: NCT07230652 · LY03020/CT-CHN-103

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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