Subjects
Eighty healthy male volunteers were screened and enrolled according to the inclusive criteria: (1) age≥18 years; (2) body mass index (BMI) of 19-26 kg/m2 (weight≥50 kg); (3) healthy conditions as confirmed by the detailed medical history, comprehensive physical examination, vital signs (e.g., systolic and diastolic blood pressure, body temperature, pulse rate), 12-lead electrocardiogram (12-ECG), virus antigen (hepatitis B and C, HIV and syphilis tests), chest X-ray and laboratory examinations (biochemistry, hematology, urinalysis, coagulation function tests); (4) restricted by concomitant drugs, tobacco, alcohol, and food supplements around the whole study. Taking any drugs that change the activity of CYP3A4 liver drug enzymes (e.g., inducers-phenobarbital, carbamazepine, phenytoin, rifampin, etc.; inhibitors-ketoconazole, itraconazole) within 28 days before taking the study drug, posaconazole, voriconazole, etc.) were excluded. All participants were supplied with a written informed consent form (ICF) prior to enrollment and were able to comply with the study constraints as published by the Phase I clinical trial center protocol. The subjects available to withdraw whenever necessary. Eighty male subjects were enrolled to explore the bioequivalence of gefitinib.
Study Design and Clinical Study Procedures
Under the fasting and fed conditions, a randomized, single-dose, and 2-period crossover study was implemented to investigate the bioequivalence of test formulation with a reference formulation in adult healthy volunteers. Subjects were screened within 14 days prior to dosing and orally treated at the dose of 250 mg.
Compared with the fasting group, the high-fat (providing about 50% of the calories in food), high-calorie (about 800~1000 kcal) meal was allocated no more than 30 min before dosing in the fed trial. For both two groups, subjects were orally administered T or R formulation with 240 ± 5 mL water. Conventional standardized meals were given at post-4 and post-10 hours to manipulate the feeding status of the subjects. The water intake restriction was strictly followed at 1 hour prior to drug administration and at 1 hour post-drug administration. Grapefruits, grapefruit juice, oranges, alcohol, coffee and strenuous exercise are not permitted during the study from 48 hours to 168 hours prior to dosing.. According to the t1/2 of gefitinib from previous reports, the washout period was fixed to 21 days[5, 6].