A Randomized Thorough QT Trial Using Concentration‐QT Analysis to Evaluate the Effects of Centanafadine on Cardiac Repolarization

Figures

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  Figure 1. Structure of centanafadine (EB‐1020) and its metabolite EB‐10601.

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  Figure 2. Mean (SD) plasma concentrations of centanafadine (A) and EB‐10601 (B) after a 800‐mg TDD of centanafadine SR and of moxifloxacin (C) after a 400‐mg single dose of moxifloxacin to healthy adults, n = 29 for centanafadine and EB‐10601 and n = 30 for moxifloxacin; lower limit of quantification in plasma was 5.00 ng/mL for centanafadine and the EB‐10601 metabolite, and 10.0 ng/mL for moxifloxacin. SD, standard deviation; SR, sustained release; TDD, total daily dose.

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  Figure 3. LS mean difference (90% CI) for time‐matched ΔQTcF by treatment, ΔQTcF, change from baseline in QTcF; CI, confidence interval; CTN SR 800 mg TDD, centanafadine sustained release tablet 800 mg total daily dose; LS, least squares.

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  Figure 4. Observed data and quantiles overlaid with linear mixed‐effects model predicted ΔΔQTcF for centanafadine (A) and EB‐10601 metabolite (B). Solid lines are linear mixed regression lines and shaded areas are the 90% CI. Solid circles denote individual data. Quantiles denote mean concentration and mean ΔΔQTcF (90% CI) for each bin. ΔΔQTcF, placebo‐corrected change from baseline in QTcF (ie, QT interval corrected using the Fridericia correction formula); CI, confidence interval.

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  Figure 5. Predicted ΔΔQTcF (primary endpoint) based on linear mixed‐effects model for centanafadine (A) and the EB‐10601 metabolite (B), maximum plasma concentration (Cmax) values obtained from PK data set. Solid red lines indicate the ΔΔQTcF at the geometric mean Cmax; ΔΔQTcF, placebo‐corrected change from baseline in QTcF (ie, QT interval corrected using the Fridericia correction formula); CI, confidence interval.