Statistical analyses
CIBIC+).Safety
SECONDARY
Based on one-sided The treated set was defined as all patients treated with at least one dose of the trial medication; these patients’ data were analyzed based on the treatment received at randomization. The full analysis set (FAS) was defined as all of the randomized patients who were treated with at least one dose of the trial medication and had a baseline and at least one corresponding post-baseline on-treatment assessment for any efficacy endpoint. These patients were analyzed based on intent-to-treat (i.e., planned treatment assigned at randomization).An MCPMod approach, in combination with a mixed model of repeated measures (MMRM), was performed for the primary analysis of the primary endpoint. This approach involved the simultaneous comparison of several plausible dose–response models, to evaluate improvements in cognition and to select the best-fitting model(s) for the dose–response relationship for ADAS-CogSix pre-defined models were tested: betaMod, Emax, sigEmax, linear, linear in log, and logistic. Except for the betaMod, the maximum effect was assumed to be achieved at the maximum dose tested. If the null hypothesis was rejected, the best-fitting model(s) was refitted to the data without assumptions to generate new estimates of the model parameters. The best-fitting model was identified based on the Akaike Information Criterion. PoCC was established if at least one model was significant.The secondary analysis of change from baseline in ADAS-CogAnalysis of covariance (ANCOVA) based on observed cases and the last observation carried forward was used for the sensitivity analysis of the primary endpoint. The model included the baseline value for the primary endpoint measure, MMSE stratification factor (≥ 20, < 20) at baseline, and treatment. Similar ANCOVA models based on observed cases were also used for the primary analysis of the secondary endpoints (ADCS-ADL and CIBIC+).Safety outcomes were analyzed descriptively.Statistical analyses were conducted using SAS version 9.4 (SAS Institute Inc., Cary, NC, USA).