Key result
For drugs with a QTc effect of around 12-14 ms, exposure response analysis applied to simulated small studies with nine subjects on drug and six on placebo resulted in a false negative rate of 5% or less.
Why the study?
Can exposure response analysis applied to small First-in-Man studies replace the thorough QT study for detecting small QTc effects?
Population
Data from five thorough QT studies, subsampled to simulate studies with 6-18 subjects on drug and 6 on…
Comparison
Exposure response analysis applied to small… vs Placebo
Design
Other
Authors
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May support QTc assessment via exposure-response analysis in small First-in-Man studies; leaves open replacement of thorough QT studies.
Can exposure response analysis applied to small First-in-Man studies replace the thorough QT study for detecting small QTc effects?
Exposure response analysis in small First-in-Man studies with careful ECG assessment can reliably detect QTc effects of 12-14 ms, potentially replacing the thorough QT study.
Ferber et al. (2014) studied Healthy volunteers (n=245). Moxifloxacin, Ketoconazole, and an investigational drug vs. Placebo was evaluated on Fraction of false negative studies (failing to exclude a QTc effect >10 ms) with 9 subjects on drug and 6 on placebo. For drugs with a QTc effect of around 12-14 ms, exposure response analysis applied to simulated small studies with nine subjects on drug and six on placebo resulted in a false negative rate of 5% or less.
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