Pharmacokinetic Bioequivalence and Safety Assessment of Two Venlafaxine Hydrochloride Extended-Release Capsules in Healthy Chinese Subjects Under Fed Conditions: A Randomized, Open-Label, Single-Dose, Crossover Study

Abstract Background and Objective Venlafaxine hydrochloride extended-release (ER) capsules are commonly used to treat depression and anxiety disorders. Evaluation of the bioequivalence of generic formulations with reference products is essential to ensure therapeutic equivalence. The objective of th...

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Main Authors: Yingxia He, Jie Wang, Fang Yao, Pan Lu, Yafang Xie, Xiuwen Li, Qiangwei Liu, Yang Liu, Dan Cao, Jun Liang, Dan Tian, Guan Liu
Format: Article
Language:English
Published: Adis, Springer Healthcare 2024-07-01
Series:Drugs in R&D
Online Access:https://doi.org/10.1007/s40268-024-00470-w
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author Yingxia He
Jie Wang
Fang Yao
Pan Lu
Yafang Xie
Xiuwen Li
Qiangwei Liu
Yang Liu
Dan Cao
Jun Liang
Dan Tian
Guan Liu
author_facet Yingxia He
Jie Wang
Fang Yao
Pan Lu
Yafang Xie
Xiuwen Li
Qiangwei Liu
Yang Liu
Dan Cao
Jun Liang
Dan Tian
Guan Liu
author_sort Yingxia He
collection DOAJ
description Abstract Background and Objective Venlafaxine hydrochloride extended-release (ER) capsules are commonly used to treat depression and anxiety disorders. Evaluation of the bioequivalence of generic formulations with reference products is essential to ensure therapeutic equivalence. The objective of this study was to evaluate the bioequivalence, safety, and tolerability of Chinese-manufactured venlafaxine hydrochloride extended-release capsules compared with USA-manufactured EFFEXOR® XR in healthy Chinese volunteers under fed conditions. Methods A randomized, open-label, single-dose, crossover study was conducted. Subjects were randomly assigned to receive the test formulation (one 150-mg ER capsule manufactured in China) or the reference formulation (one 150-mg ER capsule manufactured in the USA). The bioequivalence of the two drugs was assessed using the area under the plasma concentration–time curve from time zero to the last sampling time (AUC0–t ) and the maximum observed concentration (C max). Results A total of 28 subjects were enrolled and randomly assigned to receive a single dose of either the test or reference capsule. All the subjects completed the study and were included in the pharmacokinetic (PK) and safety analyses. The mean AUC0–t and C max of venlafaxine and its active metabolite O-desmethylvenlafaxine were comparable between the test and reference products with both parameters close to 100% and the corresponding 90% confidence intervals within the specified 80–125% bioequivalence boundary. Safety was also assessed between the two products and all adverse events (AEs) in this study were mild in severity. Conclusions Both the test and reference venlafaxine hydrochloride ER capsules were bioequivalent and showed a similar safety and tolerability profile in the population studied. Clinical Trials Registration This study was registered at the Drug Clinical Trial Registration and Information Publicity Platform ( http://www.chinadrugtrials.org.cn/index.html ) with registration number CTR20211243, date: June 1, 2021.
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spelling doaj-art-b2fa052de4514ae3870c67ce8b89b6f12025-08-20T02:23:36ZengAdis, Springer HealthcareDrugs in R&D1174-58861179-69012024-07-0124227528310.1007/s40268-024-00470-wPharmacokinetic Bioequivalence and Safety Assessment of Two Venlafaxine Hydrochloride Extended-Release Capsules in Healthy Chinese Subjects Under Fed Conditions: A Randomized, Open-Label, Single-Dose, Crossover StudyYingxia He0Jie Wang1Fang Yao2Pan Lu3Yafang Xie4Xiuwen Li5Qiangwei Liu6Yang Liu7Dan Cao8Jun Liang9Dan Tian10Guan Liu11Phase I Clinical Research Center, Wuhan Pulmonary Hospital, Wuhan Institute of Tuberculosis Prevention and ControlPhase I Clinical Research Center, Wuhan Pulmonary Hospital, Wuhan Institute of Tuberculosis Prevention and ControlPhase I Clinical Research Center, Wuhan Pulmonary Hospital, Wuhan Institute of Tuberculosis Prevention and ControlPhase I Clinical Research Center, Wuhan Pulmonary Hospital, Wuhan Institute of Tuberculosis Prevention and ControlPhase I Clinical Research Center, Wuhan Pulmonary Hospital, Wuhan Institute of Tuberculosis Prevention and ControlPhase I Clinical Research Center, Wuhan Pulmonary Hospital, Wuhan Institute of Tuberculosis Prevention and ControlPhase I Clinical Research Center, Wuhan Pulmonary Hospital, Wuhan Institute of Tuberculosis Prevention and ControlPhase I Clinical Research Center, Wuhan Pulmonary Hospital, Wuhan Institute of Tuberculosis Prevention and ControlPhase I Clinical Research Center, Wuhan Pulmonary Hospital, Wuhan Institute of Tuberculosis Prevention and ControlClinical Research Ward, The Central Hospital of WuhanTongji Medical College of Huazhong University of Science and TechnologyOffice of Clinical Research Institutions, Wuhan Pulmonary Hospital, Wuhan Institute of Tuberculosis Prevention and ControlOffice of Tuberculosis Prevention and Control, Wuhan Pulmonary Hospital, Wuhan Institute of Tuberculosis Prevention and ControlAbstract Background and Objective Venlafaxine hydrochloride extended-release (ER) capsules are commonly used to treat depression and anxiety disorders. Evaluation of the bioequivalence of generic formulations with reference products is essential to ensure therapeutic equivalence. The objective of this study was to evaluate the bioequivalence, safety, and tolerability of Chinese-manufactured venlafaxine hydrochloride extended-release capsules compared with USA-manufactured EFFEXOR® XR in healthy Chinese volunteers under fed conditions. Methods A randomized, open-label, single-dose, crossover study was conducted. Subjects were randomly assigned to receive the test formulation (one 150-mg ER capsule manufactured in China) or the reference formulation (one 150-mg ER capsule manufactured in the USA). The bioequivalence of the two drugs was assessed using the area under the plasma concentration–time curve from time zero to the last sampling time (AUC0–t ) and the maximum observed concentration (C max). Results A total of 28 subjects were enrolled and randomly assigned to receive a single dose of either the test or reference capsule. All the subjects completed the study and were included in the pharmacokinetic (PK) and safety analyses. The mean AUC0–t and C max of venlafaxine and its active metabolite O-desmethylvenlafaxine were comparable between the test and reference products with both parameters close to 100% and the corresponding 90% confidence intervals within the specified 80–125% bioequivalence boundary. Safety was also assessed between the two products and all adverse events (AEs) in this study were mild in severity. Conclusions Both the test and reference venlafaxine hydrochloride ER capsules were bioequivalent and showed a similar safety and tolerability profile in the population studied. Clinical Trials Registration This study was registered at the Drug Clinical Trial Registration and Information Publicity Platform ( http://www.chinadrugtrials.org.cn/index.html ) with registration number CTR20211243, date: June 1, 2021.https://doi.org/10.1007/s40268-024-00470-w
spellingShingle Yingxia He
Jie Wang
Fang Yao
Pan Lu
Yafang Xie
Xiuwen Li
Qiangwei Liu
Yang Liu
Dan Cao
Jun Liang
Dan Tian
Guan Liu
Pharmacokinetic Bioequivalence and Safety Assessment of Two Venlafaxine Hydrochloride Extended-Release Capsules in Healthy Chinese Subjects Under Fed Conditions: A Randomized, Open-Label, Single-Dose, Crossover Study
Drugs in R&D
title Pharmacokinetic Bioequivalence and Safety Assessment of Two Venlafaxine Hydrochloride Extended-Release Capsules in Healthy Chinese Subjects Under Fed Conditions: A Randomized, Open-Label, Single-Dose, Crossover Study
title_full Pharmacokinetic Bioequivalence and Safety Assessment of Two Venlafaxine Hydrochloride Extended-Release Capsules in Healthy Chinese Subjects Under Fed Conditions: A Randomized, Open-Label, Single-Dose, Crossover Study
title_fullStr Pharmacokinetic Bioequivalence and Safety Assessment of Two Venlafaxine Hydrochloride Extended-Release Capsules in Healthy Chinese Subjects Under Fed Conditions: A Randomized, Open-Label, Single-Dose, Crossover Study
title_full_unstemmed Pharmacokinetic Bioequivalence and Safety Assessment of Two Venlafaxine Hydrochloride Extended-Release Capsules in Healthy Chinese Subjects Under Fed Conditions: A Randomized, Open-Label, Single-Dose, Crossover Study
title_short Pharmacokinetic Bioequivalence and Safety Assessment of Two Venlafaxine Hydrochloride Extended-Release Capsules in Healthy Chinese Subjects Under Fed Conditions: A Randomized, Open-Label, Single-Dose, Crossover Study
title_sort pharmacokinetic bioequivalence and safety assessment of two venlafaxine hydrochloride extended release capsules in healthy chinese subjects under fed conditions a randomized open label single dose crossover study
url https://doi.org/10.1007/s40268-024-00470-w
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