PURPOSE: 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.
PURPOSE: 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.
Authors: Steven Harper; John A McCauley; Michael T Rudd; Marco Ferrara; Marcello DiFilippo; Benedetta Crescenzi; Uwe Koch; Alessia Petrocchi; M Katharine Holloway; John W Butcher; Joseph J Romano; Kimberly J Bush; Kevin F Gilbert; Charles J McIntyre; Kevin T Nguyen; Emanuela Nizi; Steven S Carroll; Steven W Ludmerer; Christine Burlein; Jillian M DiMuzio; Donald J Graham; Carolyn M McHale; Mark W Stahlhut; David B Olsen; Edith Monteagudo; Simona Cianetti; Claudio Giuliano; Vincenzo Pucci; Nicole Trainor; Christine M Fandozzi; Michael Rowley; Paul J Coleman; Joseph P Vacca; Vincenzo Summa; Nigel J Liverton Journal: ACS Med Chem Lett Date: 2012-03-02 Impact factor: 4.345
Authors: William Sievert; Ibrahim Altraif; Homie A Razavi; Ayman Abdo; Ezzat Ali Ahmed; Ahmed Alomair; Deepak Amarapurkar; Chien-Hung Chen; Xiaoguang Dou; Hisham El Khayat; Mohamed Elshazly; Gamal Esmat; Richard Guan; Kwang-Hyub Han; Kazuhiko Koike; Angela Largen; Geoff McCaughan; Sherif Mogawer; Ali Monis; Arif Nawaz; Teerha Piratvisuth; Faisal M Sanai; Ala I Sharara; Scott Sibbel; Ajit Sood; Dong Jin Suh; Carolyn Wallace; Kendra Young; Francesco Negro Journal: Liver Int Date: 2011-07 Impact factor: 5.828
Authors: L Wei; J Cheng; J Luo; Z P Li; J L Duan; J D Hou; M X Jia; Y Zhang; Q Huang; G J Xie; D L Wang; W Yang; C Y Zhao; G Zhao; S M Tang; G Z Lin; J J Gong; Z L Niu; J F Gao; Kopecky-Bromberg Sarah; Fredrick Linda; Mobashery Niloufar; Ye Wang; Jiefei Wang Journal: Zhonghua Gan Zang Bing Za Zhi Date: 2018-05-20