A Statistical Assessment of QT Data Following Placebo and Moxifloxacin Dosing in Thorough QT Studies

Abstract

The ICH guidelines indicate that a single “thorough QT study” should be conducted to evaluate the effects of new drugs on cardiac repolarization. A positive control, such as moxifloxacin, is required to be assessed as part of the thorough QT study to validate the assay sensitivity of each study. In order to better understand the effect of moxifloxacin, a meta-analysis of nine thorough QT studies has been undertaken to assess the overall moxifloxacin effect. The data was analyzed using a repeated measures mixed model to test various covariance structures to identify the most suitable model for this and future meta-analyses of thorough QT studies.

Key Words:

• Bazett's
• Fridericia's
• Meta-Analysis
• Moxifloxacin
• QT prolongation
• Repeated measures analysis

ACKNOWLEDGMENTS

The authors would like to thank Ian Dixon (Senior Programmer/Analyst, Discovery Biometrics, GlaxoSmithKline, UK) for his contribution to this meta-analysis.

Notes

P: Parallel group.

C: Crossover.

P: Parallel group.

C: Crossover.

X _ij where i = period and j = timepoint.

Y _ij where i = period and j = timepoint.

Y _ij where i = period and j = timepoint.

∗Baseline is mean of 3 pre-dose timepoints.