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].