A Phase I, Two-phase, Crossover Study to Evaluate the Safety, Tolerability and Pharmacokinetics of APL-1501 ER Tablets

Inclusion criteria

• The subject must have informed consent before the trial, and have a full understanding of the content, process and possible adverse reactions of the trial, and voluntarily signed a written informed consent form
• The subject is able to communicate well with the researchers and is able to complete the trial in accordance with the protocol
• 18 to 45 years old (including 18 and 45 years old)
• Postmenopausal females or sterilized participant must be at least 6 months post-menopausal, surgically sterile; the postmenopausal/sterilization should be confirmed by FSH testing
• The body weight of male subjects are ≥ 50 kg, and that of female subjects are ≥ 45 kg, and the body mass index (BMI) are between 18.0 and 30.0 kg/m2, including the boundary value. BMI= weight (kg) / height2 (m2)
• Must have normal organ functions, including the following:

• Bone marrow reserve: within normal range or deemed NCS by the treating investigator
• Hepatic: total bilirubin within normal range or deemed NCS by the treating investigator; aspartate transaminase (AST) and/or alanine aminotransferase (ALT) ≤ 1.5x ULN
• Renal: serum creatinine ≤ ULN Confidential Page 7 of 61
• Prothrombin time (PT) and partial thromboplastin time (PTT) ≤ ULN or deemed NCS by the treating investigator
• QTCF≤450 msec for males and 470 msec for females
• Healthy as determined by physician, based on a medical evaluation including Physical examination and vital signs, hematology, biochemistry, coagulation, urinalysis, and 12-lead Electrocardiograms (ECGs)
• Willingness for subjects of reproductive potential to use highly effective methods of contraception from the beginning of the study screening to the end of study follow up period a. A highly effective method of contraception is defined as one that results in a low failure rate (i.e., less than 1% per year, when used consistently and correctly)

Exclusion criteria

• History of allergy to any research drug components, similar drugs or their excipients
• History of optic nerve disorder, malignancy, anemia or gastrointestinal, liver and kidney diseases that may affect the pharmacokinetics of the investigational drugs
• Subject who is positive in one or more of the tests of hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV), and AIDS antibody (HIV)
• Subject who is positive for urine drug screening or who with a history of drug abuse
• Subject who smoked more than 5 cigarettes per day in the 3 months before the trial, and/or disagreed to avoid using any tobacco products 24 hours before administration and during hospitalization
• Regular drinkers within 6 months before the trial, that is, those who drank more than 14 units of alcohol per week (1 unit = 10 g pure alcohol), and/or those who do not agree to stop alcohol intake 24 hours before administration and during hospitalization, and/or positive in breath alcohol test. STANDARD DRINK= Volume of Alcoholic Drinks x Concentration of Alcoholic Drinks x 0.789/pure alcohol
• Systemic treatment on any investigational clinical trial within 28 days (or 5 half-lives of that agent, whichever is greater) prior to enrollment
• Subject who take strong inducers or inhibitors of metabolism enzymes or transporter within 48 h before the study, including but not limited to caffeine, xanthine, grapefruit, grapefruit juice or grapefruit-related citrus fruits (e.g. Seville oranges, pomelos) etc.
• Pregnancy or lactation
• Any other reason that in the opinion of the Investigator or Sponsor would prevent the patient from completing participation or following the study schedule