A Single- and Multiple-Dose Study to Evaluate the Pharmacokinetics of Fixed-Dose Grazoprevir/Elbasvir in Healthy Chinese Participants
Haiyan Li,1 Zhenhua Yang,1 Shuang Zhang,1 Lin Xu,1 Yudong Wei,1 Jun Jiang,2 Luzelena Caro,3 Hwa-Ping Feng,3 Jacqueline B McCrea,3 Meng Li,2 Shuang Xie,2 Jiangdian Wang,2 Xu Min Zhao,2 Shengmei Mu2 1Drug Clinical Trial Center, Peking University Third Hospital, Beijing, People’s Republic of...
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doaj-5ba2d1b73d934369bcea130b373ff7f22020-11-25T02:56:53ZengDove Medical PressClinical Pharmacology : Advances and Applications1179-14382020-02-01Volume 1211151693A Single- and Multiple-Dose Study to Evaluate the Pharmacokinetics of Fixed-Dose Grazoprevir/Elbasvir in Healthy Chinese ParticipantsLi HYang ZZhang SXu LWei YJiang JCaro LFeng HPMcCrea JBLi MXie SWang JZhao XMMu SHaiyan Li,1 Zhenhua Yang,1 Shuang Zhang,1 Lin Xu,1 Yudong Wei,1 Jun Jiang,2 Luzelena Caro,3 Hwa-Ping Feng,3 Jacqueline B McCrea,3 Meng Li,2 Shuang Xie,2 Jiangdian Wang,2 Xu Min Zhao,2 Shengmei Mu2 1Drug Clinical Trial Center, Peking University Third Hospital, Beijing, People’s Republic of China; 2Department of Infectious Diseases, MSD (China) R&D, Beijing, People’s Republic of China; 3Department of Infectious Diseases, Merck & Co., Inc., Kenilworth, NJ, USACorrespondence: Haiyan LiDrug Clinical Trial Center, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191, People’s Republic of ChinaTel +86 108 226 6226Email haiyanli1027@hotmail.comPurpose: The burden of hepatitis C virus infection is particularly high in Asian countries, and new treatments are urgently needed. The purpose of this study was to characterize the pharmacokinetics (PK) and safety of the fixed-dose combination tablet of elbasvir/grazoprevir in healthy Chinese participants.Patient and Methods: In this Phase I, single-site, open-label, 3-period study in healthy Chinese adults, participants received a single tablet of elbasvir 50 mg/grazoprevir 100 mg, followed by blood sampling for up to 96 hrs (http://www.chinadrugtrials.org.cn/ CTR20160034; Protocol PN071). Participants then received 1 tablet daily for 10 days, followed by a minimum 10-day washout, after which participants received a single dose of 2 tablets (elbasvir 100 mg/grazoprevir 200 mg). Elbasvir and grazoprevir PK were assessed following single and multiple doses. Safety and tolerability were also evaluated.Results: Twelve participants (50% male) were enrolled in and completed the study. Following single-dose oral administration of elbasvir 50 mg/grazoprevir 100 mg or elbasvir 100 mg/grazoprevir 200 mg, the median Tmax was 3– 4 hrs and elimination half-life was 18 hrs (elbasvir) and 30 hrs (grazoprevir). Multiple-dose administration resulted in AUC0– 24 accumulation ratios of 1.58 (elbasvir) and 2.35 (grazoprevir). Both elbasvir 50 mg/grazoprevir 100 mg and 100 mg/200 mg regimens were generally well tolerated.Conclusion: Single-dose administration of elbasvir 50 mg/grazoprevir 100 mg or 100 mg/200 mg and once-daily administration of elbasvir 50 mg/grazoprevir 100 mg for 10 days has been adequately characterized, with PK values within the expected range, and was generally well tolerated in healthy Chinese male and female participants.Keywords: elbasvir, grazoprevir, healthy volunteers, hepatitis C virus, pharmacokineticshttps://www.dovepress.com/a-single--and-multiple-dose-study-to-evaluate-the-pharmacokinetics-of--peer-reviewed-article-CPAAelbasvirgrazoprevirhealthy volunteershepatitis c viruspharmacokinetics |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Li H Yang Z Zhang S Xu L Wei Y Jiang J Caro L Feng HP McCrea JB Li M Xie S Wang J Zhao XM Mu S |
spellingShingle |
Li H Yang Z Zhang S Xu L Wei Y Jiang J Caro L Feng HP McCrea JB Li M Xie S Wang J Zhao XM Mu S A Single- and Multiple-Dose Study to Evaluate the Pharmacokinetics of Fixed-Dose Grazoprevir/Elbasvir in Healthy Chinese Participants Clinical Pharmacology : Advances and Applications elbasvir grazoprevir healthy volunteers hepatitis c virus pharmacokinetics |
author_facet |
Li H Yang Z Zhang S Xu L Wei Y Jiang J Caro L Feng HP McCrea JB Li M Xie S Wang J Zhao XM Mu S |
author_sort |
Li H |
title |
A Single- and Multiple-Dose Study to Evaluate the Pharmacokinetics of Fixed-Dose Grazoprevir/Elbasvir in Healthy Chinese Participants |
title_short |
A Single- and Multiple-Dose Study to Evaluate the Pharmacokinetics of Fixed-Dose Grazoprevir/Elbasvir in Healthy Chinese Participants |
title_full |
A Single- and Multiple-Dose Study to Evaluate the Pharmacokinetics of Fixed-Dose Grazoprevir/Elbasvir in Healthy Chinese Participants |
title_fullStr |
A Single- and Multiple-Dose Study to Evaluate the Pharmacokinetics of Fixed-Dose Grazoprevir/Elbasvir in Healthy Chinese Participants |
title_full_unstemmed |
A Single- and Multiple-Dose Study to Evaluate the Pharmacokinetics of Fixed-Dose Grazoprevir/Elbasvir in Healthy Chinese Participants |
title_sort |
single- and multiple-dose study to evaluate the pharmacokinetics of fixed-dose grazoprevir/elbasvir in healthy chinese participants |
publisher |
Dove Medical Press |
series |
Clinical Pharmacology : Advances and Applications |
issn |
1179-1438 |
publishDate |
2020-02-01 |
description |
Haiyan Li,1 Zhenhua Yang,1 Shuang Zhang,1 Lin Xu,1 Yudong Wei,1 Jun Jiang,2 Luzelena Caro,3 Hwa-Ping Feng,3 Jacqueline B McCrea,3 Meng Li,2 Shuang Xie,2 Jiangdian Wang,2 Xu Min Zhao,2 Shengmei Mu2 1Drug Clinical Trial Center, Peking University Third Hospital, Beijing, People’s Republic of China; 2Department of Infectious Diseases, MSD (China) R&D, Beijing, People’s Republic of China; 3Department of Infectious Diseases, Merck & Co., Inc., Kenilworth, NJ, USACorrespondence: Haiyan LiDrug Clinical Trial Center, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191, People’s Republic of ChinaTel +86 108 226 6226Email haiyanli1027@hotmail.comPurpose: The burden of hepatitis C virus infection is particularly high in Asian countries, and new treatments are urgently needed. The purpose of this study was to characterize the pharmacokinetics (PK) and safety of the fixed-dose combination tablet of elbasvir/grazoprevir in healthy Chinese participants.Patient and Methods: In this Phase I, single-site, open-label, 3-period study in healthy Chinese adults, participants received a single tablet of elbasvir 50 mg/grazoprevir 100 mg, followed by blood sampling for up to 96 hrs (http://www.chinadrugtrials.org.cn/ CTR20160034; Protocol PN071). Participants then received 1 tablet daily for 10 days, followed by a minimum 10-day washout, after which participants received a single dose of 2 tablets (elbasvir 100 mg/grazoprevir 200 mg). Elbasvir and grazoprevir PK were assessed following single and multiple doses. Safety and tolerability were also evaluated.Results: Twelve participants (50% male) were enrolled in and completed the study. Following single-dose oral administration of elbasvir 50 mg/grazoprevir 100 mg or elbasvir 100 mg/grazoprevir 200 mg, the median Tmax was 3– 4 hrs and elimination half-life was 18 hrs (elbasvir) and 30 hrs (grazoprevir). Multiple-dose administration resulted in AUC0– 24 accumulation ratios of 1.58 (elbasvir) and 2.35 (grazoprevir). Both elbasvir 50 mg/grazoprevir 100 mg and 100 mg/200 mg regimens were generally well tolerated.Conclusion: Single-dose administration of elbasvir 50 mg/grazoprevir 100 mg or 100 mg/200 mg and once-daily administration of elbasvir 50 mg/grazoprevir 100 mg for 10 days has been adequately characterized, with PK values within the expected range, and was generally well tolerated in healthy Chinese male and female participants.Keywords: elbasvir, grazoprevir, healthy volunteers, hepatitis C virus, pharmacokinetics |
topic |
elbasvir grazoprevir healthy volunteers hepatitis c virus pharmacokinetics |
url |
https://www.dovepress.com/a-single--and-multiple-dose-study-to-evaluate-the-pharmacokinetics-of--peer-reviewed-article-CPAA |
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