2.3 Study design

This was a single-center, randomized, open-label, three-cycle, three-sequence, partially replicated crossover bioequivalence study, and each cycle was followed by a 14-day washout period. The study consisted of two independent trials: a fasting trial and a postprandial trial. SAS statistical software (v9.4) was used to generate a random number table that assigned participants of the fasting trial into sequences A (TRR), B (RTR), or C (RRT) in a 1:1:1 ratio. The participants in the postprandial trial were randomly assigned into sequences D (TRR), E (RTR), or F (RRT) in the same manner.

Each participant was administered a single dose of the T or R formulation under light-proof conditions, and 240 mL of warm water was orally administered thereafter. In the fasting trial, participants fasted overnight for at least 10 h, while in the postprandial trial, they consumed a standard high-calorie and high-fat (800–1,000 kcal: protein, 150 kcal; carbohydrates, 250 kcal; and fat, 500–600 kcal) breakfast 30 min before drug administration. Water intake was restricted to 1 h before and 2 h after drug administration. The upper body was kept upright for 4 h after drug administration. Throughout the study period, alcohol consumption, strenuous activities, and smoking were prohibited. A standardized meal was provided at 4 and 10 h after treatment.