Key result
Agomelatine at single doses up to 400 mg did not prolong the QTc interval, with the upper bound of the difference from placebo remaining strictly below the 10 millisecond regulatory threshold.
Why the study?
Does agomelatine at therapeutic and supratherapeutic doses prolong the QT/QTc interval in healthy volunteers?
RCT (n=60)
double-blind
crossover
Does agomelatine at therapeutic and supratherapeutic doses prolong the QT/QTc interval in healthy volunteers?
Agomelatine at therapeutic and supratherapeutic doses does not prolong the QTc interval, indicating cardiac safety regarding repolarization.
Agomelatine up to 400 mg does not prolong QTc; confirms cardiac safety in this regulatory TQT study.
: The effects of the antidepressant agomelatine up to a supratherapeutic dose (400 mg, single dose) on the QT corrected (QTc) interval were assessed in a randomized, double-blind, placebo- and positive-controlled, crossover thorough QT/QTc study in young healthy volunteers (29 males and 31 females). The primary criterion was the study of male or female population-derived QT-corrected interval (QTcP). The main analysis on the QTcP demonstrated that among the 10 postdose measurement times planned, the largest 1-sided 95% confidence interval upper bound of the difference between agomelatine 50 mg and placebo-adjusted means, and 1 of the differences between agomelatine 400 mg and placebo-adjusted means were both strictly inferior to the 10 millisecond upper-bound threshold of regulatory concern. The assay sensitivity was established with the positive control moxifloxacin (400 mg) and detected an effect on the mean QTcP interval that is around the threshold of regulatory concern (5 milliseconds). No relationship between QTcP and plasma concentrations of agomelatine was observed. In conclusion, agomelatine up to 400 mg has no effect on the QTc interval as demonstrated in the present regulatory thorough QT/QTc study.
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Donazzolo et al. (2014) conducted an RCT in healthy volunteers (n=60). Agomelatine vs. Placebo and moxifloxacin (400 mg) was evaluated on male or female population-derived QT-corrected interval (QTcP). Agomelatine at single doses up to 400 mg did not prolong the QTc interval, with the upper bound of the difference from placebo remaining strictly below the 10 millisecond regulatory threshold.
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