Study designs
This study was a single-dose, open-label, randomized-sequence, 2-period crossover bioequivalence study. The study (Trial registration number in Subjects were randomly assigned to enter TR or RT administration sequence according to the randomized table generated by SAS version 9.4 (SAS Institute Inc., Cary, North Carolina) after being admitted to the hospital. The sample size for fasting and fed conditions was 26 and 72. It was calculated based on the results of preliminary studies by using PASS (Version 11.0.7) software. They fasted for at least 10 hours and were administered the test (T, lot # BR171203, expiration date 11/2019, Shanghai Zhaohui Pharmaceutical Co., Ltd.) or the reference (R, lot #GK8660, expiration date 12/2018, Ebewe Pharma Ges.m.b.H. Nfg.KG) product of calcium dobesilate Capsules according to their administration sequences in the next day. After a 3-day wash-out, the alternate treatment was administered in the second period. The fasting study was conducted from July 5, 2018, to July 19, 2018. The fed study was conducted from October 10, 2018, to December 3, 2018.Subjects who participated in the fed study must take a high-fat, high-calorie breakfast (about 913 kcal, including about 152 kcal protein, 263 kcal carbohydrate, and 499 kcal fat) 30 minutes before dosing and finish it within 30 minutes. Study drugs were administered with 240 mL of water under the supervision of a qualified pharmacist. Subjects were not allowed to drink water 1 hour before or after dosing, except for the water used for drug administration. Food intake was strictly controlled during the study period, any food or drink other than a uniform diet was prohibited. Standardized lunch and dinner were provided approximately 4 and 10 hours postdose, respectively.All volunteers who participated were under medical supervision by a physician throughout the study. 2 mL of blood samples were drawn into a vacuum blood collection tube containing heparin sodium. Samples were obtained at 0 (pre-dosing), 1, 2, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 10, 12, 14, and 24 hours after dosing. The sample collection in the fasting study was during July 14–15 and July 17–18, 2018. The sample collection in the fed study was during October 16–17, 19–20, 23–24, and 26–27, 2018. After sample collection, plasma was separated by centrifugation (1500 g ×10 minutes, 4°C), transferred into a polypropylene tube within 1 hour, and stored at -80°C until analyzed by LC-MS/MS method.