Primary analysis The primary efficacy analysis population will be

Primary analysis The primary efficacy analysis population will be the ITT population, comprising all randomized patients with at least selleck chemical Alisertib one baseline calculated LDL C value available and at least one calculated LDL C value available at one of the planned time points from weeks 4 to 24. The percentage change in calculated LDL C from baseline to week 24 will be analyzed using a mixed effect model with repeated measures approach to account for missing data. All available post baseline data at planned time points from week 4 to 52 regardless of status on or off treatment will be used in the MMRM for the ITT analysis, with the model used to provide least squares means estimates and comparison between treatment arms of LDL C reductions at week 24.

The models will include fixed categorical effects of treatment group, randomization strata, time point, treatment by time point interaction, and strata by time point interaction, as well as the continuous fixed covari ates of baseline LDL C value and baseline value by time point interaction. Although both trials have the LDL C differences at week 24 as the primary endpoint, they ex tend beyond 24 weeks so as to maximize available safety data and to generate further data on durability of lipid lowering effects. The studies will extend to the planned duration regardless of any efficacy data from the week 24 timepoint. Secondary analysis A hierarchical procedure will be used to control type I error and handle multiple secondary endpoint analyses. If the primary endpoint analysis is significant at 5% alpha level, key secondary efficacy endpoints will be tested sequentially in the order given in Table 2.

In par ticular, LDL C reduction at week 24 will be analyzed on treatment in the modified ITT population if the primary analysis is significant in the ITT population. The mITT population will exclude those patients from the ITT population who do not have a calculated LDL C value available while on treatment. For the on treatment analysis, all available on treatment measurements at planned time points from weeks 4 to 52 will be used in the MMRM. Continuous secondary endpoints, except Lp and TGs, will be analyzed using the same MMRM model as for the primary endpoint. Lp and TGs and the binary secondary endpoints will be analyzed using a multiple imputation approach for handling of missing values followed by robust regression or lo gistic regression.

Safety analysis AEs, la boratory parameters, and vital signs will be reported descriptively, based on the safety population. The safety analysis will focus on the treatment emergent AE period, defined as the time from the first double blind dose to the last double blind dose of the investigational product 70 days. The studies are not powered http://www.selleckchem.com/products/MG132.html to assess the im pact on cardiovascular outcomes, which will be assessed in a separate, large outcomes study.

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