Key result
Apremilast up to 50 mg twice daily does not prolong the QTc interval versus placebo.
Why the study?
This study was conducted to evaluate the effect of apremilast and its major metabolites on the placebo-corrected change-from-baseline QTc interval of an ECG.
Does apremilast prolong the QTc interval in healthy male volunteers?
RCT
Double-blind
crossover
Does apremilast prolong the QTc interval in healthy male volunteers?
Effect estimate: LS mean < 1 ms (95% CI upper limit < 10)
Apremilast at therapeutic and supratherapeutic doses does not prolong the QTc interval in healthy male volunteers.
Supports apremilast use without QTc monitoring; confirms cardiac safety in this RCT.
OBJECTIVE: This study was conducted to evaluate the effect of apremilast and its major metabolites on the placebocorrected change-from-baseline QTc interval of an electrocardiogram (ECG). MATERIALS AND METHODS: Healthy male subjects received each of 4 treatments in a randomized, crossover manner. In the 2 active treatment periods, apremilast 30 mg (therapeutic exposure) or 50 mg (supratherapeutic exposure) was administered twice daily for 9 doses. A placebo control was used to ensure doubleblind treatment of apremilast, and an openlabel, single dose of moxifloxacin 400 mg was administered as a positive control. ECGs were measured using 24-hour digital Holter monitoring. RESULTS: The two-sided 98% confidence intervals (CIs) for ΔΔQTcI of moxifloxacin completely exceeded 5 ms 2 - 4 hours postdose. For both apremilast dose studies, the least-squares mean ΔΔQTcI was < 1 ms at all time points, and the upper limit of two-sided 90% CIs was < 10 ms. There were no QT/QTc values > 480 ms or a change from baseline > 60 ms. Exploratory evaluation of pharmacokinetic/pharmacodynamic data showed no trend between the changes in QT/QTc interval and the concentration of apremilast or its major metabolites M12 and M14. CONCLUSIONS: Apremilast did not prolong the QT interval and appears to be safe and well tolerated up to doses of 50 mg twice daily.
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Palmisano et al. (2016) conducted an RCT in Healthy volunteers. Apremilast vs. Placebo was evaluated on placebo-corrected change-from-baseline QTc interval (ΔΔQTcI) (LS mean < 1 ms, 95% CI upper limit < 10). Apremilast at doses up to 50 mg twice daily did not prolong the QTc interval in healthy male volunteers, with the upper limit of the 90% CI for the placebo-corrected change from baseline <10 ms.
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