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Bioequivalence Study of Trifluridine and Tipiracil Hydrochloride Tablets on Fasting and Fed in Humans

S

Shandong New Time Pharmaceutical

Status

Completed

Conditions

Solid Tumor Cancer

Treatments

Drug: Trifluridine and Tipiracil Tablets
Drug: Lonsurf®

Study type

Interventional

Funder types

Industry

Identifiers

NCT07492173
NTP-FTDTPI-T-BE01

Details and patient eligibility

About

The test formulation of Trifluridine and Tipiracil Tablets (20 mg) is bioequivalent to the reference formulation (Lonsurf®) in Chinese patients with solid tumors under fed and fasting conditions.

Full description

This is a multicenter, randomized, open-label, two-drug, single-dose, four-cycle, crossover study aimed at evaluating the bioequivalence of the test formulation versus the reference formulation, trifluorouracil tepiazole tablets (20mg), in Chinese patients with solid tumors. The planned blood sampling time points: 0h (within 1 hour before administration) and 20 minutes, 40 minutes, 1 hour, 1 hour 20 minutes, 1 hour 40 minutes, 2 hours, 2 hours 20 minutes, 2 hours 40 minutes, 3 hours, 3 hours 20 minutes, 3 hours 40 minutes, 4 hours, 4.5 hours, 5 hours, 6 hours, 8 hours, 12 hours, 24 hours, a total of 19 points. Blood sampling time points after the meal: 0h (within 1 hour before administration) and 30 minutes, 1 hour, 1 hour 20 minutes, 1 hour 40 minutes, 2 hours, 2 hours 20 minutes, 2 hours 40 minutes, 3 hours, 3 hours 20 minutes, 3 hours 40 minutes, 4 hours, 4.5 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, a total of 19 points.

Enrollment

76 patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Subjects must meet all of the following inclusion criteria to be enrolled in this study:

  1. Aged 18-70 years (inclusive), male or female;

  2. Patients with solid tumors confirmed by histopathology or cytology;

  3. Expected survival > 3 months;

  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;

  5. Able to take oral medication (i.e., not using a feeding tube);

  6. Adequate organ function based on the following laboratory values obtained within 7 days prior to the first dose:

    1. Hemoglobin (HB) ≥ 100 g/L;
    2. Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L;
    3. Platelets (PLT) ≥ 80 × 10⁹/L;
    4. Total serum bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN);
    5. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN, or ≤ 5 × ULN in the presence of liver metastases;
    6. Creatinine clearance (Ccr) ≥ 60 mL/min;
    7. Urine protein < 2+;
    8. International normalized ratio (INR) < 1.5; activated partial thromboplastin time (APTT) and prothrombin time (PT) ≤ 1.5 × ULN;
    9. Normal electrocardiogram or electrocardiogram abnormalities determined by the investigator to be not clinically significant.

8. Female patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to the first dose and must agree to use adequate and effective contraception during the study until 6 months after discontinuation of the study drug; male patients must agree to use adequate and effective contraception during the study until 6 months after discontinuation of the study drug; 9. Patients voluntarily participate in this study and sign the informed consent form, are compliant, and can cooperate with the study observations.

Subjects who meet any of the following exclusion criteria will not be enrolled in this study:

  1. Presence of severe diseases or serious medical conditions (e.g., ileus, gastrointestinal bleeding, intestinal obstruction, pulmonary fibrosis, uncontrolled diabetes (fasting blood glucose (FBG) > 10 mmol/L), renal insufficiency, hepatic insufficiency, mental illness, cerebrovascular disease, ulcers requiring blood transfusion, etc.);

  2. Presence of ascites, pleural effusion, or pericardial effusion requiring drainage within 4 weeks prior to screening;

  3. Occurrence of myocardial infarction, severe/unstable angina pectoris, or symptomatic congestive heart failure of New York Heart Association (NYHA) class III or IV within 12 months prior to the first dose;

  4. Any clinically significant abnormality in hepatitis B virus surface antigen, Treponema pallidum specific antibody, human immunodeficiency virus antibody, or hepatitis C virus antibody;

  5. Patients with autoimmune diseases requiring immunosuppressive therapy or a history of organ transplantation;

  6. Known brain metastases or clinical symptoms suggestive of brain metastases;

  7. Presence of active infection (i.e., body temperature ≥ 38°C due to infection);

  8. Any unresolved toxicity of CTCAE grade 2 or higher from any previous treatment (excluding anemia, alopecia, skin pigmentation, and chemotherapy-induced neurotoxicity);

  9. Receipt of any of the following treatments within the specified time frame prior to screening:

    1. Major surgery within 4 weeks (major surgery: laparotomy, thoracotomy, and visceral resection by laparoscopic surgery);
    2. Any anti-tumor therapy within 2 weeks;
    3. Any investigational drug within 4 weeks;
    4. Blood transfusion within 2 weeks.
  10. Prior history of gastrectomy;

  11. Pregnant or breastfeeding women;

  12. History of allergy to Trifluridine and Tipiracil Tablets or any of their components;

  13. Patients with a history or current presence of severe interstitial pneumonia;

  14. Excessive consumption of tea, coffee, or caffeinated beverages within 3 months prior to screening (more than 8 cups per day, 1 cup = 250 mL), or consumption of any food or beverage containing alcohol, caffeine, or rich in xanthines within 48 hours prior to study drug administration (e.g., coffee, strong tea, chocolate, cola, grapefruit, etc.);

  15. Inability to adhere to a uniform diet, such as intolerance to standard meals, lactose intolerance (e.g., diarrhea after drinking milk), or dysphagia;

  16. Average daily smoking ≥ 5 cigarettes within 3 months prior to screening, or unwillingness to abstain from smoking during the study period;

  17. Alcohol abuse within 3 months prior to screening (consuming more than 14 units of alcohol per week: 1 unit ≈ 285 mL of beer, or 25 mL of spirits, or 100 mL of wine), or unwillingness to abstain from alcohol during the study period, or positive alcohol breath test result (test value > 0 mg/100 mL);

  18. History of drug abuse within the past 5 years or positive urine drug screen;

  19. Difficulty with blood collection, or needle phobia, or hemophobia, or intolerance to venipuncture;

  20. Vaccination within 2 weeks prior to screening or planned during the study period;

  21. Blood donation or other blood loss resulting in total blood loss ≥ 400 mL within 3 months prior to screening (excluding physiological blood loss in females);

  22. Any other condition that the investigator deems inappropriate for participation in this study.

Trial design

Primary purpose

Other

Allocation

Randomized

Interventional model

Crossover Assignment

Masking

None (Open label)

76 participants in 2 patient groups

Fasting
Other group
Treatment:
Drug: Lonsurf®
Drug: Trifluridine and Tipiracil Tablets
Feed
Other group
Treatment:
Drug: Lonsurf®
Drug: Trifluridine and Tipiracil Tablets

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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