New therapeutic options for persistent low-level viremia in patients with chronic hepatitis B virus infection: Increase of entecavir dosage

Table 2 Summary of principal findings from Bergman’s review on the Food and Drug Administration website

Research project in Bergman’s review	Content of research project	Registration number of clinic studies	Page in Bergman’s review
(a) Treatment of emergent adverse events	Treatment of emergent adverse events in the clinical studies in which entecavir doses from 0.5 to 40 mg/d were used to select the pivotal doses of entecavir	A 1463004, A1463005	Pages 17 and18
(b) Entecavir 0.5 and 1.0 mg/d for current treatment	The dose and dose regimen of 0.5 mg/d for NA naïve patients and 1 mg/d for lamivudine refractory patients were determined to treat CHB	A1463002, A1463005, A1463014, A1463022, A1463027	Pages 23 and 24
(c) Exposure-response: HBV DNA changes for 0.1 up to 1.0 mg/d	HBV DNA changes for 0.1, 0.5, and 1.0 mg/d were reported	A1463004, A143005, A1463014, A1463017	Pages 11-17
(d) Pharmacokinetics of multiple doses	Entecavir multiple dose pharmacokinetic parameters from 0.5 to 20 mg/d were presented	A1463002, A1463033	Page 25
(e) Overall incidence of adverse events for doses 0.5 and 1.0 mg/d	No apparent dose-response relationship in the overall incidence of adverse events for doses of 0.5 and 1.0 mg/dwasfound	A 1463004, A1463005, A1403014,	Pages 18 and 19
(f) Doses and adverse events for multiple dose therapy, 0.5 mg up to 20 mg/d	The dose and adverse events with entecavir multiple doses, 0.5 mg up to 20 mg daily, were reported in nine clinical trials	A 1463001, A1463002, A1463003, A 1463004, A1463005, A1463010, A1463033, A1463034, A1463041	Pages 17, 21, and 23
(g) Cardiovascular safety	The studies for cardiovascular safety included in vitro investigations and six clinical studies, in which the safety of entecavir was assessed at doses of 0.5 mg/d to 20 mg/d and a single dose of 40 mg	A1463001, A1463002, A1463010, A1463033, A1463034, A1463041	Pages 21 and 23

NA: Nucleos(t)ide analogs; CHB: Chronic hepatitis B virus infection; HBV: Hepatitis B virus.