A Randomized, Double-Blind, Parallel Design Thorough QT Study With a Nested Crossover to Compare the Cardiac Safety of Amiselimod With Placebo and Positive Control in Healthy Volunteers
Abstract
This double-blind study evaluated the cardiac safety of amiselimod. Healthy adults (n = 190) were randomized (2:1:1) to receive (1) oral placebo (day -1), followed by oral amiselimod (days 1-26), which was upwardly titrated from 0.4 to 1.6 mg once daily to achieve steady-state concentrations comparable with 0.4 (therapeutic) and 0.8 mg (supratherapeutic) once daily, and placebo (day 27); (2) placebo (day -1), oral moxifloxacin 400 mg (day 1; positive control), followed by placebo (days 1-27); or (3) placebo (days -1 to 26), followed by moxifloxacin 400 mg (day 27). No participant had a corrected QT interval by Fredericia (QTcF) >500 milliseconds or a change from baseline (dQTcF) >60 milliseconds. The upper limits of the 90%CIs for the differences in least-squares mean difference in dQTcF between amiselimod and placebo on days 13 and 26 were <10 milliseconds. Area under the concentration-time curve from 0 to 23.5 hours after dosing and maximum plasma concentration of amiselimod and amiselimod-P (active metabolite) at steady-state concentrations for the 0.8-mg dose on day 26 were approximately double that observed with the 0.4-mg dose on day 13. All adverse events were mild to moderate in severity, and no deaths occurred. Amiselimod did not have any clinically relevant effect on the QTcF interval.
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 190 participants or records.
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