Safety, Tolerability and Pharmacokinetics of CBP-174 in Healthy Adults

A Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study in Healthy Subjects to Evaluate the Safety, Tolerability, and Pharmacokinetics of CBP-174 After Oral Administration

The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of CBP-174 after a single oral dose in healthy adult subjects.

This is a randomized, double-blind, placebo-controlled, single ascending dose study in healthy subjects to evaluate the safety, tolerability and pharmacokinetics of CBP-174 compared to placebo. The study plans to set 6 dose escalation cohorts with single oral dose. Each subject will receive only one dose regimen in this study and the total duration to participate the study is approximately 1 to 4-week.

Inclusion Criteria:

Subjects will be enrolled into the study only if they meet ALL of the following inclusion criteria:

1. Subjects are fully informed of the study, and are willing to participate in the study and sign the informed consent document prior to any procedure
2. Healthy male and female subjects, aged 18 to 55 years (both inclusive)
3. Body mass index is between 18 and 32 kg/m2 (both inclusive), the weight of male subjects ≥ 50 kg, the weight of female subjects ≥ 45 kg
4. Considered generally normal or abnormal with no clinical significance upon medical history, physical examination, vital signs, ECG, and clinical laboratory tests, as judged by the Investigator
5. Female subjects of child-bearing potential must agree to use highly effective contraceptive methods 1 month before the screening, during the entire study, and within 3 months after the end of this study, and have no egg donation plan within 3 months of study end. The male partner of a female subject must agree to use condoms during the screening, entire study, and within 3 months after the end of this study. Male subjects considered fertile must agree to not plan to father a child, donate sperm, and take effective contraceptive methods during the screening, entire study, and within 3 months after the end of this study. The female partner of male subjects must agree to use a highly effective method of female contraception (Section 9.8.3.2) during the screening, entire study, and within 3 months after the end of this study. Contraceptive requirements applies to subjects in same sex relationships for male and female subjects, female subjects of non child bearing potential or male subjects with female partners of non-childbearing potential.
6. Subjects who are able to communicate well with Investigators, as well as understand and adhere to the requirements of this study

Exclusion Criteria:

Subjects will be excluded from the study, if they meet ANY of the following criteria:

Subjects will be excluded from the study, if they meet ANY of the following criteria:

1. Subjects who have difficulties in venous blood collection or history of dizziness with blood or needles

2. Female subjects who have a positive pregnancy test or are breastfeeding

3. Subjects who have allergy/hypersensitivity history to any excipient of CBP-174 solution, or hypersensitivity to antihistamines, or severe allergies at the discretion of Investigator

4. Exposure to any other investigational medicinal product or any other clinical trial within 30 days or 5 times half-lives (whichever is longer) before dosing current study medication

5. Subjects who have a history of gastrointestinal (such as duodenal ulcer, alimentary tract hemorrhage, etc.), liver or kidney disease, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs

6. Subjects who have a history of significant eye diseases (such as keratitis, and scleritis, etc.) or clinical significant eye signs (conjunctiva hyperemia, etc.)

7. Subjects who have a history of attention deficit disorder (ADD) or attention deficit hyperactivity disorder (ADHD)

8. Subjects who have a history of sleep disorders within 2 years before the screening visit or score highly on the PSQI or ISI questionaire; or have a history of epilepsy or other seizure disorder

   *Pittsburgh Sleep Quality Index (PSQI) ≥ 8 or Insomnia Severity Index (ISI) ≥ 8

9. Subjects who have the medical history of other significant diseases (including but not limited to pulmonary, cardiovascular, gastrointestinal, hematological endocrinological, immunological, dermatological, malignant diseases, mental and nervous systems, and other related diseases) or any other disease/ailment at the discretion of the Investigator

10. Subjects with any of the following clinical laboratory tests results at screening:

    a Aspartate aminotransferase (AST) > 1.5 × the upper limit of normal (ULN)

    b Alanine aminotransferase (ALT) > 1.5 × ULN

    c Serum creatinine > 1.2 × ULN; or creatinine clearance < 60 mL/min (calculated by the Cockcroft-Gault)

    *The clinical laboratory tests of hematology, blood biochemistry, or urinalysis could be allowed repeat once if Investigator considers it necessary

11. Subjects whose QTcF interval prolongation at screening (male: QTcF interval ≥ 450 ms, female: QTcF interval ≥ 470 ms)

12. Blood donation or blood loss more than 400 mL within 3 months before the screening visit

13. Subjects with a known history of drug abuse within 2 years before the screening visit; or positive drug abuse at screening

14. Weekly alcohol consumption of more than 14 units of alcohol (1 unit of alcohol = 360 mL of beer or 45 mL of spirit with the alcohol content of 40% or 150 mL of wine) in any week within the past 3 months before the screening visit; or intake of alcohol-containing products within 48 hours before the first dose, or cannot abstain from any alcohol product during the study, or positive breath alcohol test at screening or check-in (Day -1）

15. Smoking history (> 5 cigarettes per day) within 3 months before the screening visit, or cannot abstain from any tobacco products during the study, or positive urine nicotine test before randomization

16. Excessive drinking of tea, coffee, or caffeine-containing beverage (at least 8 cups per day, 1 cup = 250 mL) any day within 3 months before screening; intake of rich caffeine- or xanthine-containing food or drinks that may produce caffeine or xanthine after being metabolized (eg, coffee, tea, chocolate, cola drinks) within 48 hours before the first dose

17. Any marketed medication (prescription and nonprescription drugs) within 14 days before the first dose or within 5 times the elimination half-life or pharmacodynamic half-life of the medication (excluding oral contraceptives and low dose paracetamol at the discretion of the Investigator, or topical ointments at the discretion of the Investigator)

18. Administration of a Coronavirus Disease 2019 (COVID-19) vaccine in the past 14 days prior to dosing

19. Use of herbal medicines, dietary supplements and vitamin within 14 days before the first dose(permissible at the discretion of the Investigator)

20. Subjects who have a major surgery within 3 months before the first dose or who plan to undergo surgery during the study

21. Positive screening test for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C antibody

22. Subjects who are determined as not eligible to participate in this study by the Investigator