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Exploration of suitable pharmacodynamic parameters for acarbose bioequivalence evaluation: A series of clinical trials with branded acarbose

AIMS: To determine deficiencies in the Food and Drug Administration (FDA)'s guidance for assessing acarbose bioequivalence (BE) and to explore optimal pharmacodynamic (PD) metrics for better evaluation of acarbose BE. METHODS: Three clinical trials with branded acarbose were conducted in health...

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Autores principales: Huang, Jie, Liu, Wen‐yu, Yu, Jing‐jing, Yang, Jin‐bo, Li, Min, Zou, Chan, Guo, Cheng‐xian, Yang, Xiao‐yan, Yang, Shuang, Xie, Jin‐lian, Huang, Zhi‐jun, Chen, Hui, Pei, Qi, Yang, Guo‐ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576622/
https://www.ncbi.nlm.nih.gov/pubmed/32333407
http://dx.doi.org/10.1111/bcp.14324
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author Huang, Jie
Liu, Wen‐yu
Yu, Jing‐jing
Yang, Jin‐bo
Li, Min
Zou, Chan
Guo, Cheng‐xian
Yang, Xiao‐yan
Yang, Shuang
Xie, Jin‐lian
Huang, Zhi‐jun
Chen, Hui
Pei, Qi
Yang, Guo‐ping
author_facet Huang, Jie
Liu, Wen‐yu
Yu, Jing‐jing
Yang, Jin‐bo
Li, Min
Zou, Chan
Guo, Cheng‐xian
Yang, Xiao‐yan
Yang, Shuang
Xie, Jin‐lian
Huang, Zhi‐jun
Chen, Hui
Pei, Qi
Yang, Guo‐ping
author_sort Huang, Jie
collection PubMed
description AIMS: To determine deficiencies in the Food and Drug Administration (FDA)'s guidance for assessing acarbose bioequivalence (BE) and to explore optimal pharmacodynamic (PD) metrics for better evaluation of acarbose BE. METHODS: Three clinical trials with branded acarbose were conducted in healthy subjects, including a pilot study (Study I, n = 11, 50 and 100 mg), a 2×2 crossover BE study (Study II, n = 36, 100 mg) and a 4×4 Williams study (Study III, n = 16, 50/100/150 mg). Serum glucose concentrations were measured by the glucose oxidase method. RESULTS: In Study I, compared with 50 mg acarbose, only 100 mg acarbose had a significantly lower C(max0–4h) than that of sucrose administration alone (7.96 ± 0.83 mmol/L vs 6.78 ± 1.02 mmol/L, P < .05). In Study II, the geometric mean ratios of the test formulation to the reference formulation (both formulations were the branded drug) for FDA PD metrics, ΔC(max0–4h) and ΔAUC(0–4h), were 0.903 and 0.776, respectively, and the 90% confidence intervals were 67.44–120.90 and 53.65–112.13, respectively. The geometric mean ratios (confidence interval) for possible optimal evaluation PD metrics (C(max0–2h) and AUC(0–2h)) were 1.035 (94.23–112.68) and 0.982 (89.28–107.17), respectively. Further, C(max0–2h) and AUC(0–2h) also met the sensitivity requirements for BE evaluation in Study III. CONCLUSION: Considering the mechanisms of action of acarbose, the PD effect was shown to be dose independent during the 2–4 hours postadministration of acarbose. Hence PD metrics based on the serum glucose concentration from 0 to 2 hours (C(max0–2h) and AUC(0–2h)) are more sensitive than the FDA‐recommended PD metrics for acarbose BE evaluation from 0–4 hours (ΔC(max0–4h) and ΔAUC(0–4h)). The trial has been registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn, ChiCTR1800015795, ChiCTR‐IIR‐17013918, ChiCTR‐IIR‐17011903). All subjects provided written informed consent before screening.
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spelling pubmed-75766222020-10-23 Exploration of suitable pharmacodynamic parameters for acarbose bioequivalence evaluation: A series of clinical trials with branded acarbose Huang, Jie Liu, Wen‐yu Yu, Jing‐jing Yang, Jin‐bo Li, Min Zou, Chan Guo, Cheng‐xian Yang, Xiao‐yan Yang, Shuang Xie, Jin‐lian Huang, Zhi‐jun Chen, Hui Pei, Qi Yang, Guo‐ping Br J Clin Pharmacol Original Articles AIMS: To determine deficiencies in the Food and Drug Administration (FDA)'s guidance for assessing acarbose bioequivalence (BE) and to explore optimal pharmacodynamic (PD) metrics for better evaluation of acarbose BE. METHODS: Three clinical trials with branded acarbose were conducted in healthy subjects, including a pilot study (Study I, n = 11, 50 and 100 mg), a 2×2 crossover BE study (Study II, n = 36, 100 mg) and a 4×4 Williams study (Study III, n = 16, 50/100/150 mg). Serum glucose concentrations were measured by the glucose oxidase method. RESULTS: In Study I, compared with 50 mg acarbose, only 100 mg acarbose had a significantly lower C(max0–4h) than that of sucrose administration alone (7.96 ± 0.83 mmol/L vs 6.78 ± 1.02 mmol/L, P < .05). In Study II, the geometric mean ratios of the test formulation to the reference formulation (both formulations were the branded drug) for FDA PD metrics, ΔC(max0–4h) and ΔAUC(0–4h), were 0.903 and 0.776, respectively, and the 90% confidence intervals were 67.44–120.90 and 53.65–112.13, respectively. The geometric mean ratios (confidence interval) for possible optimal evaluation PD metrics (C(max0–2h) and AUC(0–2h)) were 1.035 (94.23–112.68) and 0.982 (89.28–107.17), respectively. Further, C(max0–2h) and AUC(0–2h) also met the sensitivity requirements for BE evaluation in Study III. CONCLUSION: Considering the mechanisms of action of acarbose, the PD effect was shown to be dose independent during the 2–4 hours postadministration of acarbose. Hence PD metrics based on the serum glucose concentration from 0 to 2 hours (C(max0–2h) and AUC(0–2h)) are more sensitive than the FDA‐recommended PD metrics for acarbose BE evaluation from 0–4 hours (ΔC(max0–4h) and ΔAUC(0–4h)). The trial has been registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn, ChiCTR1800015795, ChiCTR‐IIR‐17013918, ChiCTR‐IIR‐17011903). All subjects provided written informed consent before screening. John Wiley and Sons Inc. 2020-05-26 2020-11 /pmc/articles/PMC7576622/ /pubmed/32333407 http://dx.doi.org/10.1111/bcp.14324 Text en © 2020 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Huang, Jie
Liu, Wen‐yu
Yu, Jing‐jing
Yang, Jin‐bo
Li, Min
Zou, Chan
Guo, Cheng‐xian
Yang, Xiao‐yan
Yang, Shuang
Xie, Jin‐lian
Huang, Zhi‐jun
Chen, Hui
Pei, Qi
Yang, Guo‐ping
Exploration of suitable pharmacodynamic parameters for acarbose bioequivalence evaluation: A series of clinical trials with branded acarbose
title Exploration of suitable pharmacodynamic parameters for acarbose bioequivalence evaluation: A series of clinical trials with branded acarbose
title_full Exploration of suitable pharmacodynamic parameters for acarbose bioequivalence evaluation: A series of clinical trials with branded acarbose
title_fullStr Exploration of suitable pharmacodynamic parameters for acarbose bioequivalence evaluation: A series of clinical trials with branded acarbose
title_full_unstemmed Exploration of suitable pharmacodynamic parameters for acarbose bioequivalence evaluation: A series of clinical trials with branded acarbose
title_short Exploration of suitable pharmacodynamic parameters for acarbose bioequivalence evaluation: A series of clinical trials with branded acarbose
title_sort exploration of suitable pharmacodynamic parameters for acarbose bioequivalence evaluation: a series of clinical trials with branded acarbose
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576622/
https://www.ncbi.nlm.nih.gov/pubmed/32333407
http://dx.doi.org/10.1111/bcp.14324
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