Fig. 4
Concentration-QTc analysis. A linear model with a treatment effect-specific intercept was fitted for lucerastat and moxifloxacin plasma concentrations. For lucerastat, a QTcF effect above 10 ms could be excluded up to a plasma concentration of approximately 34 μg/mL, whereas moxifloxacin caused a clear QTc prolongation. a Lucerastat and b moxifloxacin. Left panel: scatter plots of observed plasma concentrations and estimated placebo-adjusted ΔQTcF by subject. The solid red lines with dashed red lines denote the predicted mean ΔΔQTcF with 90% CI. The blue squares, red triangles, and black circles denote the pairs of observed lucerastat plasma concentrations and estimated placebo-adjusted ΔQTcF by subject for lucerastat 1000 mg, lucerastat 4000 mg, and placebo, respectively (a). The green diamonds and black circles denote the pairs of observed moxifloxacin plasma concentrations and estimated placebo-adjusted ΔQTcF by subject for moxifloxacin and placebo, respectively (b). Right panel: relationship between lucerastat (a) and moxifloxacin (b) plasma concentrations and predicted ΔΔQTcF. The solid black lines with gray shaded area denote the predicted mean (90% CI) ΔΔQTcF. The blue, red, and green areas denote the predicted mean (90% CI) ΔΔQTcF with blue square, red triangle, and green diamond at the geometric mean (90% CI) Cmax of lucerastat 1000 mg, lucerastat 4000 mg, and moxifloxacin 400 mg, respectively. The dashed black lines represent the thresholds for clinically concerning QTc prolongation (a) and for demonstrating assay sensitivity (b). CI, confidence interval; Cmax, maximum plasma concentration; Δ, change-from-baseline; ΔΔ, placebo-corrected change-from-baseline; QTcF, Fridericia-corrected QTc