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

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

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.

Inclusion Criteria:

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.

Exclusion Criteria:

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.