ALT flares were defined according to AASLD criteria [18]. Glomerular filtration rates (GFR) at each visit were estimated using both the Cockcroft-Gault [19] and the Modification Of Diet In Renal Disease Study (MDRD) equations [20], [21]. Statistical Analysis The primary efficacy Vorinostat endpoint was analyzed as a binary variable using last-observation-carried-forward (LOCF) imputation. The primary endpoint and all binary secondary endpoints were summarized at each visit, with the 95% confidence interval calculated using the normal approximation method for binomial proportion. Differences in baseline demographics and disease characteristics between patients who remained on telbivudine monotherapy through Week 52 and those who added tenofovir after Week 24 were assessed for significance using Fisher��s exact test for categorical variables and two-sided t-tests for continuous variables.

Changes from baseline in GFR at Week 52 were assessed for significance using two-sided, paired t-tests. Statistical analyses were carried out using SAS ver 1.3 (SAS Institute, Inc. Carey, NC, USA). The full intention-to-treat (ITT) population comprised all patients who received at least one dose of telbivudine. As this was a study of a specific therapeutic algorithm, a per-protocol population was derived for efficacy assessments �C i.e. the efficacy population �C which excluded one patient with a confirmed baseline rtM204I resistance mutation to telbivudine/lamivudine, 2 patients lost to follow-up before Week 24, and 2 protocol violators who did not receive tenofovir despite detectable Week 24 HBV DNA.

The safety population for adverse event monitoring comprised the full ITT population as defined. This was a single-arm study, hence the sample size was not based on power for statistical comparison between treatment groups. The primary objective was Brefeldin_A to demonstrate antiviral efficacy by estimating the proportion of patients with HBV DNA <300 copies/mL at Week 52. Based on the pivotal phase III GLOBE study (NCT00057265) [15], approximately 44% of patients treated with telbivudine were anticipated to have HBV DNA <300 copies/mL at Week 24, of whom 95% would still be <300 copies/mL at Week 52. By contrast, it was assumed from GLOBE data that only 34% of patients with HBV DNA of 300 copies/mL or above at Week 24 would fall to below 300 copies/mL by Week 52 on telbivudine monotherapy, giving an overall proportion of 60% with <300 copies/mL at Week 52. It was assumed that adding tenofovir at Week 24 for those with ��300 HBV DNA copies/mL would increase the proportion who subsequently fell to <300 copies/mL at Week 52 to at least 50%.