Evaluation of the Food Effecton the Pharmacokinetics of FWD1802 in Healthy Subjects

A Phase I, Single-Center, Open-Label, Randomized, Single-Dose, Three-Period Crossover Study to Evaluate the Effect of High-Fat and Low-Fat Meals on the Pharmacokinetics of FWD1802 in Chinese Healthy Subjects

A Phase I, Single-Center, Open-Label, Randomized, Single-Dose, Three-Period Crossover Study to Evaluate the Effect of High-Fat and Low-Fat Meals on the Pharmacokinetics of FWD1802 in Chinese Healthy Subjects. The primary objectives are to address the following questions:

To evaluate the impact of high-fat and low-fat meals on the pharmacokinetic (PK) characteristics of a single oral dose of FWD1802 in healthy Chinese Subjects.

A Phase I, single-center, open-label, randomized, single-dose, three-period crossover study conducted in Chinese healthy subjects to evaluate the effect of high-fat and low-fat meals on the pharmacokinetics of FWD1802.

A total of 18 healthy subjects are planned to be enrolled. Subjects will be randomly assigned in a 1:1:1 ratio to one of three sequences. Each sequence consists of three cycles, with one dose administered per cycle, and a washout period of ≥14 days between consecutive doses. The three sequences are as follows:

Sequence 1: Cycle 1 - administration under fasting conditions; Cycle 2 - administration after a low-fat meal; Cycle 3 - administration after a high-fat meal.

Sequence 2: Cycle 1 - administration after a low-fat meal; Cycle 2 - administration after a high-fat meal; Cycle 3 - administration under fasting conditions.

Sequence 3: Cycle1 - administration after a high-fat meal; Cycle 2 - administration under fasting conditions; Cycle 3 - administration after a low-fat meal.

Notes:

1. Fasting Condition (Reference): A single dose of 150 mg FWD1802 is taken orally after fasting for at least 10 hours (water is allowed as needed).
2. Low-Fat Meal: A single dose of 150 mg FWD1802 is taken orally after a low-fat meal.
3. High-Fat Meal: A single dose of 150 mg FWD1802 is taken orally after a high-fat meal.
4. Low-Fat Meal: Total calories approximately 400-500 Kcal, with fat constituting approximately 25% of the total caloric content.
5. High-Fat Meal: A high-calorie (approximately 800-1000 Kcal) and high-fat meal (fat constituting approximately 50% of the total caloric content), with approximately 150, 250, and 500-600 Kcal derived from protein, carbohydrates, and fat, respectively. The composition of the high-fat and low-fat meals must be consistent across all cycles.

Inclusion Criteria:

• Subjects must meet all of the following inclusion criteria to be eligible for enrollment in this study:

  1. The subject understands the trial's objectives, nature, methods, and potential adverse reactions, voluntarily participates, and signs the informed consent form, ensuring that all trial procedures will be personally undertaken by the subject.
  2. Chinese male or female subjects, aged 18-45 years (inclusive) for males and 18-50 years (inclusive) for females at the time of screening.
  3. Body mass index (BMI) between 19.0 and 28.0 kg/m² (inclusive); body weight ≥50.0 kg for males and ≥45.0 kg for females.
  4. Results from screening assessments, including medical history inquiry, vital signs [body temperature (tympanic), pulse, blood pressure (seated)], comprehensive physical examination, laboratory tests (complete blood count, blood chemistry, urinalysis, coagulation function), 12-lead electrocardiogram (ECG), abdominal ultrasound (liver, gallbladder, pancreas, spleen, kidneys), and chest X-ray (posteroanterior view), are all within normal limits or show abnormalities that are not clinically significant.
  5. Female subjects have no pregnancy plan and voluntarily agree to use effective contraceptive measures (Appendix 1) from 2 weeks prior to the first dose until 6 months after the last dose / Male subjects have no pregnancy plan for their partners and voluntarily agree to use effective contraceptive measures (Appendix 1) from the first dose until 6 months after the last dose, with no plans for sperm or egg donation.

Exclusion Criteria:

• Subjects who meet any of the following exclusion criteria will not be eligible for enrollment in this study:

  1. History or presence of clinically significant diseases requiring exclusion, including but not limited to disorders of the nervous, cardiovascular, hematological and lymphatic, immune, renal, hepatic, gastrointestinal, psychiatric, ophthalmological, respiratory, metabolic, and skeletal systems.
  2. History of severe allergies (including allergic constitution, drug allergies, allergies to two or more types of food, etc.) or known hypersensitivity to FWD1802 and/or any of its excipients.
  3. Special dietary requirements or inability to tolerate a high-calorie (approximately 800-1000 Kcal per meal) and high-fat (fat constituting approximately 50% of total caloric intake) diet.
  4. History of dysphagia or any gastrointestinal disease that may affect drug absorption (including but not limited to gastrointestinal dysfunction, total/partial gastrectomy, gastrointestinal bleeding/ulcer, malabsorption syndrome, uncontrolled nausea/vomiting/diarrhea, etc.).
  5. Undergone surgery within 3 months prior to screening or planned surgery during the study period.
  6. Intolerance to venipuncture, history of needle phobia/blood phobia, or difficulty with blood collection.
  7. History of drug abuse or positive urine drug abuse screening (at baseline).
  8. Regular alcohol consumption exceeding 21 units per week within 3 months prior to screening (1 unit = 360 mL of beer, 150 mL of wine, or 45 mL of 40% spirits) or positive alcohol breath test (at baseline).
  9. Smoking history of more than 10 cigarettes per day within 3 months prior to screening.
  10. Excessive consumption of tea, coffee, and/or caffeine-rich beverages (average >8 cups per day, 1 cup = 250 mL) within 3 months prior to screening.
  11. Donated blood or experienced significant blood loss (≥400 mL), or received blood transfusion or blood products within 3 months prior to the first dose.
  12. Participation in another clinical trial involving an investigational drug and receipt of the study drug within 3 months prior to the first dose, with an interval less than 5 half-lives of the previously administered drug.
  13. Use of any moderate/strong CYP3A4 inhibitors or inducers, P-glycoprotein (P-gp) inhibitors, or drugs that suppress gastric acid production (e.g., proton pump inhibitors, PPIs) within 28 days prior to the first dose (refer to Table 3 for CYP3A4 and P-gp inhibitors/inducers and PPI inhibitors).
  14. Use of prescription drugs, over-the-counter medications, dietary supplements, or herbal medicines within 14 days prior to the first dose.
  15. Consumption of chocolate, any food or beverage containing caffeine or xanthine, grapefruit, or grapefruit-related citrus fruits (e.g., pomelo) or juices within 48 hours prior to dosing in each cycle.
  16. Positive screening result for hepatitis B surface antigen, hepatitis C antibody, human immunodeficiency virus (HIV) antibody, or Treponema pallidum antibody; or history of active or latent tuberculosis (TB).
  17. History of any QT interval prolongation (including from previous studies) or known risk factors (e.g., hypokalemia, hypomagnesemia, or recent use of drugs known to prolong QTcF); or during screening, a resting 12-lead electrocardiogram (ECG) showing a corrected QTcF >450 ms, PR interval >210 ms, or QRS complex >120 ms; or resting heart rate ≤60 bpm.
  18. Ophthalmological examination abnormalities at screening, other than refractive errors, deemed clinically significant by the investigator.
  19. Vaccination within 4 weeks prior to screening.
  20. Unwillingness or inability to comply with the lifestyle guidelines described in the study protocol (e.g., dietary restrictions, activity, and contraceptive requirements).
  21. Any other factors considered by the investigator as unsuitable for participation in this trial.