Clinical–Liver, Pancreas, and Biliary TractEntecavir Therapy for up to 96 Weeks in Patients With HBeAg-Positive Chronic Hepatitis B
Section snippets
Study Design
This study was a double-blind, double-dummy, randomized, controlled trial comparing the safety and efficacy of entecavir 0.5 mg once daily and lamivudine 100 mg once daily in patients with HBeAg-positive CHB. The study had a 52-week blinded treatment phase, followed by an extended blinded treatment phase for up to 44 additional weeks (96 weeks total). A total of 715 patients were recruited into the first year of the study between December 2001 and September 2002 from 137 centers worldwide.
At
Study Population
Of the 709 patients randomized and treated in the first year of the study (entecavir, 354; lamivudine, 355), 74 entecavir-treated patients (21%) and 67 lamivudine-treated patients (19%) achieved response at week 48, discontinued therapy after week 52, and were followed for up to 24 weeks off-treatment.22 Nineteen entecavir-treated patients (5%) and 94 lamivudine-treated patients (26%) had nonresponse at week 48 and were to discontinue therapy at week 52. A total of 247 entecavir-treated
Discussion
The current study provided controlled data documenting the efficacy of entecavir compared with lamivudine, when each was continued for up to 96 weeks. Within the second-year treatment cohort (virologic responders at week 48), response rates to entecavir continued to improve during extended treatment. The proportion of patients achieving an undetectable HBV DNA level (<300 copies/mL) increased from 64% at week 48 to 74% at the end of dosing. This 10% increment in virologic response was
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The study was sponsored by Bristol-Myers Squibb. The sponsor designed the study in collaboration with expert hepatologists. The sponsor also collected the data, monitored study conduct, performed the statistical analyses, and coordinated writing of the manuscript with all authors. The study was conducted in accordance with the ethics principles of the Declaration of Helsinki and in line with Good Clinical Practice guidelines and applicable local regulatory requirements. Written informed consent was obtained from all participants, and financial disclosures were documented and submitted to the U.S. Food and Drug Administration. Statistical analyses were performed in accordance with the Good Clinical Practice guidelines, and the product was subsequently approved by the U.S. Food and Drug Administration. R.G.G. had full access to all the data and accepts full responsibility for the veracity of the data and analysis.
The authors declare the following conflicts of interest: R.G.G. received a research grant from, and is an advisor to, Bristol-Myers Squibb, A.S.L. received a research grant from Bristol-Myers Squibb, A.S.L., A.G., and K.-H.H. are advisors for Bristol-Myers Squibb, and M.H., J.Y., R.C., H.B.-S. are employees of Bristol-Myers Squibb. T.-T.C., R.A.D., J.S., Y.-C.C., and S.-D.L. have no financial arrangements to disclose.