A Study of LY03015 in Healthy Chinese and Caucasian Adult Subjects

An Open-Label, Single-Dose, Parallel-Group Study to Evaluate the Pharmacokinetics, Safety and Tolerability of LY03015 in Healthy Chinese and Caucasian Adult Subjects

This is an open-label, single-dose, parallel-group study to evaluate the safety, tolerability and pharmacokinetic characteristics of LY03015 in healthy Chinese and Caucasian adult subjects. The duration of study will be around up to 42 days for each participant, including up to 14 days of screening period, baseline visit, and a 28-day safety assessment period with a 7-day/6-night stay in the clinical research unit.

A total of 24 subjects (12 Chinese, 12 Caucasians) will be enrolled. A single dose of 20 mg LY03015 will be administered orally under fasting condition. The primary objective is to characterize the pharmacokinetic (PK) profiles of LY03015 following a single oral administration in healthy Chinese and Caucasian adult subjects. The secondary objective is to evaluate the safety and tolerability of a single oral dose of LY03015.

Inclusion Criteria:

• Age 18 to 45 years, inclusive.

• In good health, based on detailed medical history, clinical laboratory tests, vital signs, physical examinations, and ECGs per Investigator's judgment.

• Body mass index (BMI) is between 18.5 and 28 kg/m2, inclusive, and body weight ≥ 50 kg at screening.

• Specific ethnicity:

  1. Chinese participant: born in China to Chinese parents, with both maternal and paternal grandparents must not have lived outside of China for more than 5 years, and lifestyle, including dietary habits, must have remained largely unchanged since relocating from China.
  2. Caucasian participant: born of Caucasian parents and both maternal and paternal grandparents must have largely maintained their usual lifestyle and diet.

• All female subjects must have a negative pregnancy test result at both screening and baseline. If of childbearing potential (WOCBP) and heterosexually active, practicing or agree to practice a highly effective contraception method of birth control. Highly effective methods of birth control must be used for at least 21 days prior to study drug dosing, throughout the study, and for at least 30 days after dosing to minimize the risk of pregnancy.

• Sexually active fertile male subjects must be willing to use acceptable contraception methods from study drug dosing, throughout the study, and for at least 30 days after dosing if their partners are women of child-bearing potential.

Exclusion Criteria:

• Known history of hypersensitivity to VMAT2 inhibitors; or allergic to any ingredient of the investigational drug.
• Clinically significant past medical history in the judgement of the Investigator, would interfere with the subject's ability to participate in the study.
• History of depression, akathisia, agitation, restlessness, parkinsonism, or neuroleptic malignant syndrome (NMS).
• History of suicide attempts in the past 12 months and/or evident history of risk of suicide or homicide as assessed by the Investigator.
• Known history of gastric ulceration or gastrointestinal bleeding; or inability to swallow the study drug or having gastrointestinal dysfunction that, in the Investigator's judgment, would affect drug absorption.
• Known history or current substance abuse including alcohol, nicotine, and illegal drugs; urine drug screen or alcohol test positive at screening or baseline.
• Known history of syncope during blood draws or injections, or inability to tolerate intravenous paracentesis.
• Malignancies within 5 years with exception of cured basal cell or squamous cell skin cancer prior to screening.
• Clinically significant abnormal findings in vital signs, laboratory tests, and

ECGs at screening or baseline, including but not limited to:

1. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 1.5 times the upper limit of normal (ULN);

2. Serum creatinine > ULN;

3. Estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m²;

4. QT interval corrected by Fridericia's formula (QTcF) >450 msec for males and >460 msec for females; or a prior history or presence of circumstances that could increase the risk of torsade de pointes or sudden death in association with the use of study drug that prolong the QTc interval, or other clinically significant ECG findings upon the Investigator's decision.

   • Use of any prescription medications within 28 days prior to dosing; use of any Over- the-counter (OTC) medications including herbal supplements, minerals, and vitamins within 7 days prior to dosing.
   • Undergo surgery within 4 weeks prior to screening or plan to have surgery during the study.
   • Hepatitis B surface antigen (HBsAg), hepatitis C (HCV) antibody, or Human immunodeficiency virus (HIV) with positive test result.
   • Donation or blood collection of > 1 unit (approximate 450 mL) of blood (or blood products) or acute loss of blood during the 90 days prior to screening.
   • Receipt of another investigational product within 1 month, or 5 half-lives of the other investigational product, whichever is longer, prior to screening.