Background and objective: Entecavir (ETV) is a standard of care for chronic hepatitis B (CHB). In a bioequivalence study, ETV from Dong-A ST (Baracle®) was found to have a pharmacokinetic profile equivalent to ETV from Bristol-Myers Squibb (BMS) (Baraclude®). The present study was conducted to evaluate the antiviral activity and safety of ETV from Dong-A ST in comparison to ETV from BMS in patients with CHB. Methods: In this multicenter, double-blind, active-controlled, stratified-randomized, parallel group, comparative trial, 118 treatment-naïve patients with CHB were randomly assigned to receive either 0.5 mg of ETV from Dong-A ST or ETV from BMS once daily for 48 weeks. The primary efficacy endpoint was virologic improvement (a mean reduction from baseline in serum HBV DNA levels) at 24 weeks. Secondary efficacy endpoints included a mean reduction in serum HBV DNA levels at 48 weeks, proportion of patients with undetectable levels of serum HBV DNA, rates of hepatitis B e antigen (HBeAg) loss and seroconversion, rates of HBsAg loss and seroconversion, and rates of normalization of alanine aminotransferase (ALT) levels. Results: From baseline to week 24, HBV DNA levels (log10) decreased by 4.81 and 4.63 with ETV from Dong-A ST and with ETV from BMS, respectively. The upper limit of two-sided 95% confidence intervals (CI) (equivalent to one-sided 97.5% CIs) for the difference between the treatment groups was 0.208, which was below the noninferiority margin of 1, thus supporting the noninferiority of ETV from Dong-A ST in comparison to ETV from BMS. No statistically significant differences were noted between the treatment groups in all secondary and tertiary efficacy endpoints. Safety profiles were also similar between the two groups. Conclusion: In patients with previously untreated HBeAg-positive or negative HBV infection, the efficacy of ETV from Dong-A ST was noninferior to that of ETV from BMS, and there were no significant differences in efficacy or safety between two groups.
Bibliographical noteFunding Information:
This study was sponsored by Dong-A ST Co., the manufacturer of Baracle®. Dong-A ST Co. made significant contributions to the design and analysis of the study, and assisted in preparation of research grant applications. The following investigators and institutions participated in the study: Han Chu Lee (Asan Medical Center), Si Hyun Bae (The Catholic University of Korea Seoul St Mary’s Hospital), Ju Hyun Kim (Gachon University Gil medical Center), Jae Seok Hwang (Keimyung University Dongsan Medical Center), So Young Kwon (Konkuk University Medical Center), Won Young Tak (Kyungpook National University Hospital), Jong Eun Yeon (Korea University Guro Hospital), Sang Young Han (Dong-A University Hospital), Joon Hyeok Lee (Samsung Medical Center), Jung Hwan Yoon (Seoul National University Hospital), Do Young Kim (Severance Hospital Yonsei University), Neung Hwa Park (Ulsan University Hospital), Youn Jae Lee (Inje University Busan Paik Hospital), Sung Hoon Kim (Chonbuk National University Hospital), Byung Seok Lee (Chungnam National University Hospital), Byung Hoon Han (Kosin University Gospel Hospital), Yong Geun Cho (Presbyterian Medical Center), and Dae Won Chun (Hanyang University Medical Center). None of the investigators have a conflict of interest with regard to this study.
© 2017 Kim et al.
All Science Journal Classification (ASJC) codes
- Pharmaceutical Science
- Drug Discovery