This difference was driven largely by the increased incidence of hepatic flares in the placebo group. Serious adverse events that were considered by the investigator to be related to study medication occurred in four patients, one in the tenofovir DF group (hepatitis) and three in the placebo group (two with

increased ALT and one with abdominal pain). No deaths occurred during the study. All adverse events occurring in ≥5% of patients are listed in Table 3. The most common adverse events were pharyngitis, nasopharyngitis, increased ALT, acne, and upper respiratory tract infection. The only adverse events for which there was a statistically significant between-group difference (all higher in the placebo group) were increased ALT (tenofovir DF, 6%; placebo, 22%; P = 0.024), acne (tenofovir DF, 4%; placebo, 19%; P = 0.029), and lymphadenopathy (tenofovir DF, 0%; placebo, 11%; P = 0.027). One patient in the tenofovir DF group discontinued the study Selleckchem LBH589 due to syncope. This patient had a history of syncope, and this adverse event was not considered to be related to study medication. Two patients in the placebo group were discontinued due to sustained grade 4 ALT elevation for ≥16 weeks and were enrolled in the open-label phase of the study at week 40 (Fig. 1). No patients in either group experienced Luminespib a ≥6% decrease in lumbar spine BMD at any time

during the study. Five patients, three in the tenofovir DF group and two in the placebo group, had a decrease

of >4% in lumbar spine BMD. None of these patients experienced a bone fracture or other bone-related adverse event. The mean change in lumbar spine BMD z score from baseline to week 72 was −0.05 in the tenofovir DF group and 0.07 in the placebo group. Corresponding mean change in whole-body BMD z scores from baseline to week 72 were −0.15 and 0.06, respectively. Both treatment groups experienced an overall increase in mean lumbar spine BMD. There was a greater increase in mean BMD in the placebo group than the tenofovir DF group at all visits at which BMD was measured: weeks 24 (tenofovir DF, 2%; placebo, 3%; P = 0.005), 48 selleck inhibitor (tenofovir DF, 4%; placebo, 6%; P = 0.046), and 72 (tenofovir DF, 5%; placebo, 8%; P = 0.053). There were no observed grade 3 or 4 increases in serum creatinine or decrease in serum phosphorus, and no patient had a confirmed increase from baseline creatinine of ≥0.5 mg/dL. Eight patients, six in the tenofovir DF group and two in the placebo group, had a confirmed increase in serum creatinine of 0.3 mg/dL. All of these elevations were transient or within the normal range. The mean change in creatinine from baseline to week 72 was 0.1 mg/dL in both treatment groups. Hepatobiliary adverse events were reported in three patients in the tenofovir DF group (all cases of hepatitis) and 10 patients in the placebo group (eight cases of hypertransaminasemia and two cases of hepatomegaly).