PMID- 36369609 OWN - NLM STAT- MEDLINE DCOM- 20221129 LR - 20221129 IS - 1179-6901 (Electronic) IS - 1174-5886 (Print) IS - 1174-5886 (Linking) VI - 22 IP - 4 DP - 2022 Dec TI - Pharmacokinetics, Bioequivalence and Safety of Cloperastine in Chinese Healthy Subjects Under Fasting and Postprandial Conditions. PG - 311-320 LID - 10.1007/s40268-022-00406-2 [doi] AB - BACKGROUND: Cloperastine is a pivotal antibechic widely prescribed to treat cough caused by respiratory diseases. The present trial evaluated the pharmacokinetics (PK), bioequivalence (BE) and safety effects of the generic test (T) tablet of cloperastine after single-dose administration of cloperastine, compared with the original reference (R) tablet of cloperastine. OBJECTIVE: The purpose of this trial was to compare the PK, BE and safety of a test 10 mg versus the reference 10 mg formulation of cloperastine under fasting and postprandial conditions in healthy Chinese volunteers. METHODS: A single-centre, randomised, open, double-cycle, self-crossover, single oral administration Phase I trial was performed in healthy Chinese volunteers. A total of 60 subjects were enrolled in either the fasting (28 subjects) or the postprandial condition (32 subjects). Subjects randomly received a single dose of the T or R preparation (10 mg dose). Plasma concentrations of cloperastine were analysed by a validated LC-MS/MS method. The primary endpoints of the PK parameters were the area under the plasma concentration-time curve from zero to 72 h (AUC(0-72h)), under the plasma concentration-time curve from zero to infinity (AUC(0-infinity)) and the maximal plasma concentration (C(max)). The equivalence standard range (80.0-125.0%) was used to evaluate the BE of the two preparations. The safety parameter as secondary endpoint was mainly evaluated by the occurrence of adverse events (AEs). RESULTS: A total of 25 and 30 subjects in the fasting and postprandial conditions completed this clinical trial, respectively. The geometric mean ratio (GMR) of the T/R for the C(max), AUC(0-72h) and AUC(0-infinity) were 102.1%, 103.8% and 104.0% in the fasting condition, respectively. In the postprandial condition, the GMR of the T/R for the C(max), AUC(0-72h) and AUC(0-infinity) were 94.2%, 98.8% and 99.0%, respectively. All the values fell within the range (80.0-125.0%). The C(max) and AUC(0-72h) values of the T and R preparations in fasting and postprandial conditions were not statistically significant (P > 0.05). Furthermore, no serious adverse events (SAEs) occurred during the whole trial. CONCLUSIONS: The T and R preparations were bioequivalent under both conditions. Food has no significant effect on the absorption of cloperastine. Moreover, T and R preparations were well tolerated. The trial registration number (TRN) and date of registrations were CTR20212515, 13 October 2021. CI - (c) 2022. The Author(s). FAU - Luo, Hong-Yu AU - Luo HY AUID- ORCID: 0000-0003-3357-9154 AD - School of Pharmacy, Department of Pharmacy, Phase I Clinical Trial Centre, Changsha Central Hospital Affiliated to University of South China, University of South China, Hengyang, China. FAU - Long, Hui-Zhi AU - Long HZ AD - School of Pharmacy, Department of Pharmacy, Phase I Clinical Trial Centre, Changsha Central Hospital Affiliated to University of South China, University of South China, Hengyang, China. FAU - Zhou, Zi-Wei AU - Zhou ZW AD - School of Pharmacy, Department of Pharmacy, Phase I Clinical Trial Centre, Changsha Central Hospital Affiliated to University of South China, University of South China, Hengyang, China. FAU - Xu, Shuo-Guo AU - Xu SG AD - School of Pharmacy, Department of Pharmacy, Phase I Clinical Trial Centre, Changsha Central Hospital Affiliated to University of South China, University of South China, Hengyang, China. FAU - Li, Feng-Jiao AU - Li FJ AD - School of Pharmacy, Department of Pharmacy, Phase I Clinical Trial Centre, Changsha Central Hospital Affiliated to University of South China, University of South China, Hengyang, China. FAU - Cheng, Yan AU - Cheng Y AD - School of Pharmacy, Department of Pharmacy, Phase I Clinical Trial Centre, Changsha Central Hospital Affiliated to University of South China, University of South China, Hengyang, China. FAU - Wen, Dan-Dan AU - Wen DD AD - School of Pharmacy, Department of Pharmacy, Phase I Clinical Trial Centre, Changsha Central Hospital Affiliated to University of South China, University of South China, Hengyang, China. FAU - Deng, Ping AU - Deng P AD - School of Pharmacy, Department of Pharmacy, Phase I Clinical Trial Centre, Changsha Central Hospital Affiliated to University of South China, University of South China, Hengyang, China. FAU - Gao, Li-Chen AU - Gao LC AD - School of Pharmacy, Department of Pharmacy, Phase I Clinical Trial Centre, Changsha Central Hospital Affiliated to University of South China, University of South China, Hengyang, China. 89206346@qq.com. LA - eng GR - 2016SK2066/Science and Technology Key Program of Hunan Province Grants/ GR - 201940/WT_/Wellcome Trust/United Kingdom GR - 20201904/Science and Technology Key Program of Hunan Provincial Health Committee/ GR - 2021JJ30753/Natural Science Foundation of Hunan Province/ GR - YNKY202205/Changsha Central Hospital Affiliated to University of South China Foundation of key Program/ GR - 225 Program/Hunan Province Foundation of High-level Health Talent/ GR - 201940/WT_/Wellcome Trust/United Kingdom PT - Clinical Trial, Phase I PT - Journal Article PT - Randomized Controlled Trial DEP - 20221111 PL - New Zealand TA - Drugs R D JT - Drugs in R&D JID - 100883647 RN - 69M5L7BXEK (cloperastine) RN - 0 (Tablets) SB - IM MH - Humans MH - Therapeutic Equivalency MH - *Fasting MH - Chromatography, Liquid MH - Healthy Volunteers MH - *Tandem Mass Spectrometry MH - Tablets MH - China PMC - PMC9651896 COIS- The authors declare no conflicts of interest in this work. EDAT- 2022/11/13 06:00 MHDA- 2022/11/30 06:00 PMCR- 2022/11/11 CRDT- 2022/11/12 00:49 PHST- 2022/10/16 00:00 [accepted] PHST- 2022/11/13 06:00 [pubmed] PHST- 2022/11/30 06:00 [medline] PHST- 2022/11/12 00:49 [entrez] PHST- 2022/11/11 00:00 [pmc-release] AID - 10.1007/s40268-022-00406-2 [pii] AID - 406 [pii] AID - 10.1007/s40268-022-00406-2 [doi] PST - ppublish SO - Drugs R D. 2022 Dec;22(4):311-320. doi: 10.1007/s40268-022-00406-2. Epub 2022 Nov 11.