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...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Dove Medical Press
2020
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/5ba2d1b73d934369bcea130b373ff7f2 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:5ba2d1b73d934369bcea130b373ff7f2 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:5ba2d1b73d934369bcea130b373ff7f22021-12-02T12:06:34ZA Single- and Multiple-Dose Study to Evaluate the Pharmacokinetics of Fixed-Dose Grazoprevir/Elbasvir in Healthy Chinese Participants1179-1438https://doaj.org/article/5ba2d1b73d934369bcea130b373ff7f22020-02-01T00:00:00Zhttps://www.dovepress.com/a-single--and-multiple-dose-study-to-evaluate-the-pharmacokinetics-of--peer-reviewed-article-CPAAhttps://doaj.org/toc/1179-1438Haiyan 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, pharmacokineticsLi HYang ZZhang SXu LWei YJiang JCaro LFeng HPMcCrea JBLi MXie SWang JZhao XMMu SDove Medical Pressarticleelbasvirgrazoprevirhealthy volunteershepatitis c viruspharmacokineticsTherapeutics. PharmacologyRM1-950ENClinical Pharmacology: Advances and Applications, Vol Volume 12, Pp 1-11 (2020) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
elbasvir grazoprevir healthy volunteers hepatitis c virus pharmacokinetics Therapeutics. Pharmacology RM1-950 |
| spellingShingle |
elbasvir grazoprevir healthy volunteers hepatitis c virus pharmacokinetics Therapeutics. Pharmacology RM1-950 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 |
| 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 |
| format |
article |
| 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 |
| 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 |
| publishDate |
2020 |
| url |
https://doaj.org/article/5ba2d1b73d934369bcea130b373ff7f2 |
| work_keys_str_mv |
AT lih asingleandmultipledosestudytoevaluatethepharmacokineticsoffixeddosegrazoprevirelbasvirinhealthychineseparticipants AT yangz asingleandmultipledosestudytoevaluatethepharmacokineticsoffixeddosegrazoprevirelbasvirinhealthychineseparticipants AT zhangs asingleandmultipledosestudytoevaluatethepharmacokineticsoffixeddosegrazoprevirelbasvirinhealthychineseparticipants AT xul asingleandmultipledosestudytoevaluatethepharmacokineticsoffixeddosegrazoprevirelbasvirinhealthychineseparticipants AT weiy asingleandmultipledosestudytoevaluatethepharmacokineticsoffixeddosegrazoprevirelbasvirinhealthychineseparticipants AT jiangj asingleandmultipledosestudytoevaluatethepharmacokineticsoffixeddosegrazoprevirelbasvirinhealthychineseparticipants AT carol asingleandmultipledosestudytoevaluatethepharmacokineticsoffixeddosegrazoprevirelbasvirinhealthychineseparticipants AT fenghp asingleandmultipledosestudytoevaluatethepharmacokineticsoffixeddosegrazoprevirelbasvirinhealthychineseparticipants AT mccreajb asingleandmultipledosestudytoevaluatethepharmacokineticsoffixeddosegrazoprevirelbasvirinhealthychineseparticipants AT lim asingleandmultipledosestudytoevaluatethepharmacokineticsoffixeddosegrazoprevirelbasvirinhealthychineseparticipants AT xies asingleandmultipledosestudytoevaluatethepharmacokineticsoffixeddosegrazoprevirelbasvirinhealthychineseparticipants AT wangj asingleandmultipledosestudytoevaluatethepharmacokineticsoffixeddosegrazoprevirelbasvirinhealthychineseparticipants AT zhaoxm asingleandmultipledosestudytoevaluatethepharmacokineticsoffixeddosegrazoprevirelbasvirinhealthychineseparticipants AT mus asingleandmultipledosestudytoevaluatethepharmacokineticsoffixeddosegrazoprevirelbasvirinhealthychineseparticipants AT lih singleandmultipledosestudytoevaluatethepharmacokineticsoffixeddosegrazoprevirelbasvirinhealthychineseparticipants AT yangz singleandmultipledosestudytoevaluatethepharmacokineticsoffixeddosegrazoprevirelbasvirinhealthychineseparticipants AT zhangs singleandmultipledosestudytoevaluatethepharmacokineticsoffixeddosegrazoprevirelbasvirinhealthychineseparticipants AT xul singleandmultipledosestudytoevaluatethepharmacokineticsoffixeddosegrazoprevirelbasvirinhealthychineseparticipants AT weiy singleandmultipledosestudytoevaluatethepharmacokineticsoffixeddosegrazoprevirelbasvirinhealthychineseparticipants AT jiangj singleandmultipledosestudytoevaluatethepharmacokineticsoffixeddosegrazoprevirelbasvirinhealthychineseparticipants AT carol singleandmultipledosestudytoevaluatethepharmacokineticsoffixeddosegrazoprevirelbasvirinhealthychineseparticipants AT fenghp singleandmultipledosestudytoevaluatethepharmacokineticsoffixeddosegrazoprevirelbasvirinhealthychineseparticipants AT mccreajb singleandmultipledosestudytoevaluatethepharmacokineticsoffixeddosegrazoprevirelbasvirinhealthychineseparticipants AT lim singleandmultipledosestudytoevaluatethepharmacokineticsoffixeddosegrazoprevirelbasvirinhealthychineseparticipants AT xies singleandmultipledosestudytoevaluatethepharmacokineticsoffixeddosegrazoprevirelbasvirinhealthychineseparticipants AT wangj singleandmultipledosestudytoevaluatethepharmacokineticsoffixeddosegrazoprevirelbasvirinhealthychineseparticipants AT zhaoxm singleandmultipledosestudytoevaluatethepharmacokineticsoffixeddosegrazoprevirelbasvirinhealthychineseparticipants AT mus singleandmultipledosestudytoevaluatethepharmacokineticsoffixeddosegrazoprevirelbasvirinhealthychineseparticipants |
| _version_ |
1718394691606544384 |