The effects of apremilast on the QTc interval in healthy male volunteers: a formal, thorough QT study.
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).


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.
Maria
M
Palmisano
Anfan
A
Wu
Mahmoud
M
Assaf
Liangang
L
Liu
C Hyung
CH
Park
Ishani
I
Savant
Yong
Y
Liu
Simon
S
Zhou
D000328:Adult; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004562:Electrocardiography / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D058988:Phosphodiesterase 4 Inhibitors / Q000494:pharmacology*; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000494:pharmacology
D058988:Phosphodiesterase 4 Inhibitors; D013792:Thalidomide; C505730:apremilast