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

## TL;DR

This study tested if centanafadine, a drug for ADHD, affects heart rhythms and found it is safe with no significant impact on heart repolarization.

## Contribution

The study provides new evidence that centanafadine does not significantly affect cardiac repolarization in healthy adults.

## Key findings

- Centanafadine and its metabolite showed no statistically significant effect on QTc intervals.
- Moxifloxacin demonstrated expected QTc prolongation, confirming the trial's sensitivity.
- No serious adverse events or clinically meaningful heart changes were observed with centanafadine.

## Abstract

Centanafadine is a norepinephrine/dopamine/serotonin reuptake inhibitor in development for treatment of attention‐deficit/hyperactivity disorder. This double‐blind, placebo‐ and moxifloxacin‐controlled, 3‐period crossover trial evaluated the effects of centanafadine (EB‐1020) and its metabolite (EB‐10601) on cardiac repolarization in 30 healthy adults (18‐65 years). Dosing sequences included centanafadine sustained‐release 800 mg (supratherapeutic) total daily dose, placebo, and moxifloxacin 400 mg. Electrocardiogram parameters and heart rate (HR) were assessed. The primary endpoint was placebo‐corrected change from baseline QTc (ΔΔQTc), analyzed using concentration‐QTc (C‐QTc) analysis. The C‐QTc slopes for centanafadine (−0.001 ms/[ng/mL]) and EB‐10601 (−0.0003 ms/[ng/mL]) were not statistically significant. Assay sensitivity was confirmed by the statistically significant C‐QTc slope for moxifloxacin (0.004 ms/[ng/mL]) and a 2‐sided 90% confidence interval lower bound >5 milliseconds. No change from baseline in QTcF or placebo‐corrected QTcF ≥10 milliseconds for centanafadine was observed at any postdose time point. No centanafadine‐treated participants had QTcF increases of >30 milliseconds and no relevant PR/QRS interval or HR increases were observed. The predicted ΔΔQTcF values of centanafadine, EB‐10601, and moxifloxacin at the geometric mean Cmax were −2.72, −1.59, and 11.75 milliseconds, respectively. No serious treatment‐emergent adverse events or deaths were reported. Centanafadine was generally safe and well‐tolerated, with no clinically meaningful effect on cardiac repolarization.