Safety All adverse events (AEs) occurring during the study were recorded, and their possible link find more to the study treatment was assessed. Statistical Analysis The statistical analysis was carried out on the intent-to-treat (ITT) population, defined as all Batimastat cell line patients who took at least one dose of the study treatment and had a least one post-enrollment evaluation. In the case of missing data, the analysis took into account the last evaluation available according to the last-observation-carried-forward

(LOCF) technique. The safety analysis was carried out on all patients who took at least one dose of the study treatment. The sample size for the primary outcome was calculated on the basis of data from previous hot flash studies, as described by Sloan et al.[33] In these, data from the placebo arms showed differences in hot flash activity (between baseline and the end of the first treatment period) of a standard deviation (SD) of two

hot flashes and 5 score units per patient per day. From this, it was shown that 50 patients per group provided 80% power to detect differences Ganetespib price in average hot flash activity of 0.58 SDs, and that 50 patients per treatment arm provided 80% power to detect an average shift of 1.2 hot flashes per day or an HFS of 3 units per day.[33] With this approach and our hypothesis that there would be a (clinically relevant) difference of 3 points in the HFS in favor of the active (BRN-01) arm and an Erastin datasheet SD of 5, sample size estimates were calculated

using nQuery Advisor (version 6.01) software. We found that a sample size of 49 in each group was required to show this outcome with an α error rate of 5% in a unilateral situation and with a power of 90%. Quantitative data are described as the number, mean, and SD. Qualitative data are described as the absolute and relative frequencies with 95% confidence intervals (CIs). Comparisons of means were carried out by analysis of variance (ANOVA) or by using the Kruskal-Wallis test if the distribution was not normal. Comparisons of percentages were carried out using the χ2 test or Fisher’s exact test if the conditions for use of the χ2 test were not fulfilled. Where appropriate, comparisons over time were performed using the Student’s t-test. The evolution of the HFS in the two groups was assessed by analysis of the area under the curve (AUC) of the mean scores recorded weekly from each patient in each group over the duration of the study, including those at enrollment (before any treatment).