Muscle velocity recovery cycles as pharmacodynamic biomarker: Effects of mexiletine in a randomized double‐blind placebo‐controlled cross‐over study

Figures

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  FIGURE 1. Effects of mexiletine versus placebo on early supernormality after five conditioning stimuli (5ESN), shown as the estimated mean change from baseline at 3‐ and 5‐h postdose. Error bars indicate the 95% confidence interval of the estimated mean.

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  FIGURE 2. Effects of mexiletine versus placebo on the difference in late supernormality of five versus one conditioning stimuli (5XLSN), shown as the estimated mean change from baseline at 3‐ and 5‐h postdose. Error bars indicate the 95% confidence interval of the estimated mean.

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  FIGURE 3. Mean postdose recordings of recovery cycles with five conditioning stimuli (CS), for mexiletine (black, filled) and placebo (gray, empty). Error bars show the standard error. The upper graph shows the percentual latency change after five conditioning stimuli at different interstimulus intervals. The lower graph shows the additional change in latency of five versus one conditioning stimuli. Variables with significant effects (mexiletine vs. placebo) are visualized by indicating the name of the variable. Variable visualization is reproduced from ref. [11]. Note this graph is meant to visualize treatment effects, but does not fully reflect the statistical analysis, because the statistical model includes baseline as a covariate which is not reflected in the graph.

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  FIGURE 4. Effects of mexiletine versus placebo on the latency change after a 15 Hz train of stimuli (Lat[15 Hz]last), shown as the estimated mean change from baseline at 3‐ and 5‐ h postdose. Error bars indicate the 95% confidence interval of the estimated mean.

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  FIGURE 5. Effects of mexiletine versus placebo on the latency change at the end of a 30 Hz train of stimuli (Lat[30 Hz]last), shown as the estimated mean change from baseline at 3‐ and 5‐ h postdose. Error bars indicate the 95% confidence interval of the estimated mean.

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  FIGURE 6. Mean postdose recordings of frequency ramp, for mexiletine (black) and placebo (gray). Dotted lines show the standard error. The upper graph shows the percentual latency (compared to unconditioned latency) by a train of pulses (stimulation rate shown in the lowest graph). The middle graph shows the percentual amplitude change (compared to unconditioned amplitude values). Both graphs show the last‐in‐train values. Variables with significant effects (mexiletine vs. placebo) are visualized by indicating the name of the variable. Variable visualization is reproduced from ref. [11]. Note this graph is meant to visualize treatment effects, but does not fully reflect the statistical analysis, the statistical model includes baseline as a covariate which is not reflected in the graph.