br Methods br Results Between August and November

Methods
Results Between August and November 2011, one hundred eighteen (118) males were recruited from the toll like receptor (Fig. 1). The baseline characteristics are presented in Table 1. From all participants, who received placebo or trastuzumab (Fig. 1), 261 routine chemistry and haematology follow-up observations were included in the analysis, as well as 30 follow-up echocardiographic examinations, 259 body weights, and 316 measurements for NT-proBNP (1373kg from baseline to 63days post-dose, without changes in laboratory parameters. Creatinine concentration and NT-proBNP did not differ significantly from placebo. The total protein time profile (Fig. 3) seems to suggest that the difference between the trastuzumab group and placebo is solely attributable to an absolute change from baseline in the placebo group. Interestingly, however, at 8days post-administration the total protein concentration in both groups had increased in a comparable fashion. The protein concentration-time profile in the trastuzumab group was thus characterised by a minor decrease and/or lag time of multiple days before increasing, whereas the profile in the placebo group could be described by a linear increase. Albumin and thrombocyte concentrations displayed a similar phenomenon of a minor decrease and/or lag time in the trastuzumab group. Clinically significant changes or trends on either individual or group level could not be discerned for any of the other laboratory parameters. All participants had returned to baseline by either 8 or 63±7days post-treatment (Fig. 3). Treatment effects on the echocardiographic parameters were less straightforward (Table 4). The LVEF increased relatively by 1·9% compared to placebo. Fractional shortening (FS) followed the LVEF closely. The deceleration time (DT) and TAPSE values increased with a mean difference versus placebo of respectively 31·0% and 9·9%, whereas S′ and E′ values remained stable (Fig. 4). The only echocardiographic parameter that changed significantly was the E/A-ratio, which differed from placebo 0·57 (0·21–0·93, p=0·0034) at 3–5days post-dose. In the analysis on the extended dataset, including also the baseline effects of participants who received the biosimilar product, all contrasts between trastuzumab and placebo remained virtually unaltered (Tables 3 and 4), with the exception of the contrast for DT. Probably the baseline variability on this parameter was greater in the entire study population than in the trastuzumab arm (Table 1). Treatment effects on other echocardiographic parameters (e.g. LVEF, E/A-ratio, TAPSE) also became less pronounced.