Statistical considerations
Three patient populations were considered in analyses: (i) The per protocol (PP) population, including all randomized patients who received at least one treatment dose and had all primary endpoint measurements and no major protocol deviations; (ii) the intention-to-treat (ITT) population, including all randomized patients; (iii) and the safety population, with all randomized patients who received at least one dose of the study treatment. The PP population dataset was the only population considered for the primary analysis.For univariate analysis, the quantitative variables were described using central tendency and dispersion measures, including mean, standard deviation (SD), median and interquartile range (IQR). To define qualitative variables, total counts and percentages were used.For bivariate analysis between distinct subjects, quantitative variables were analyzed using the Student's t-test for independent samples or the Mann–Whitney U test when samples were not normally distributed. Qualitative variables were analyzed using the Chi-square test or the Fisher test. For intra-subject variables, quantitative variables were analyzed using the Student's t-test or the Wilcoxon signed-rank test, depending on whether the samples were or were not normally distributed.Missing data were discarded in the analyses, and a significance level of 0.05 was used in statistical testing. All statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS) version 22.0 (SPSS Inc, Chicago, USA).