Eltrombopag does not affect cardiac repolarization: Results from a definitive QTc study in healthy subjects

Categoría Estudio primario
RevistaBritish journal of clinical pharmacology
Año 2010
Cargando información sobre las referencias
AIM To evaluate the effect of eltrombopag on cardiac repolarization and to characterize the relationship between plasma eltrombopag concentrations and change in QTc. METHODS This was a double-blind, placebo- and active-controlled, randomized, balanced four-period, crossover study in healthy men and women. Subjects were randomized to receive eltrombopag 50 mg and 150 mg, moxifloxacin 400 mg (positive control) and placebo in one of four sequences. RESULTS Eighty-seven subjects entered the study and 48 completed. There was no prolongation of QTc (Fridericia) following eltrombopag treatment, as the upper limit of the 90% confidence interval (CI) for the time-matched change from baseline in QTcF between drug and placebo (ddQTcF) did not exceed 10 ms for eltrombopag at either dose. Maximum observed mean treatment difference was 2.29 ms (90% CI 0.34, 4.24) for eltrombopag 150 mg at 1 h post-dose and 11.64 ms (90% CI 9.64, 13.64) for moxifloxacin 400 mg at 4 h. Eltrombopag Cmax and AUC(0,24 h) increased in a dose proportional manner between 50 mg and 150 mg after 5 days' dosing. Proportions of subjects with adverse events were similar across treatments (52-66% of subjects). Most withdrawals (26/39 subjects) were due to elevated platelets. Three subjects were withdrawn for ventricular premature beats (one following each active treatment) reported as related to the study drug. CONCLUSIONS No clinically significant QTc prolongation was observed for eltrombopag at therapeutic and supratherapeutic doses. © 2010 The British Pharmacological Society.
Epistemonikos ID: b2d8302d0d1d0328914d500310d9df7a46c785c1
First added on: Mar 18, 2020