OBJECTIVE: This randomized, double-blind, placebo- and positive-controlled 4-way crossover study evaluated the effects of tapentadol immediate release (IR) on the QT/QTc interval. MATERIALS AND METHODS:Healthy subjects received tapentadol IR 100 mg or 150 mg, or placebo, every 6 h on Days 1 and 2, with a >= 7-day washout between treatments. Moxifloxacin 400 mg was the positive control. Serial triplicate 12-lead electrocardiograms (ECGs) were performed; the Fridericia correction (QTcF) was the primary correction method. Serial blood sampling was performed for pharmacokinetic analyses. RESULTS: Of the 75 subjects who were randomized, 68 received at least 1 dose of study medication, and 59 completed the study. Upper limits of the 90% confidence intervals (CIs) for the difference in mean DeltaQTcF between tapentadol IR 100 or 150 mg and placebo were < 10 ms (non-inferiority criterion) for all time points. The lower limit of the 90% CI for mean DeltaQTcF between moxifloxacin and placebo exceeded 5 ms from 1 to 6 h after dosing, establishing assay sensitivity. No subject had a postdose QTc interval > 480 ms, change from baseline > 60 ms, or clinically relevant change in heart rate or other ECG variables. Steady-state concentrations were reached within 18 to 24 h. Common adverse events were vertigo (central nervous system (CNS) origin), headache, somnolence, nausea, vomiting, and feeling drunk. CONCLUSION: Therapeutic and supratherapeutic doses of tapentadol do not affect the QT/QTc interval.
RCT Entities:
OBJECTIVE: This randomized, double-blind, placebo- and positive-controlled 4-way crossover study evaluated the effects of tapentadol immediate release (IR) on the QT/QTc interval. MATERIALS AND METHODS: Healthy subjects received tapentadol IR 100 mg or 150 mg, or placebo, every 6 h on Days 1 and 2, with a >= 7-day washout between treatments. Moxifloxacin 400 mg was the positive control. Serial triplicate 12-lead electrocardiograms (ECGs) were performed; the Fridericia correction (QTcF) was the primary correction method. Serial blood sampling was performed for pharmacokinetic analyses. RESULTS: Of the 75 subjects who were randomized, 68 received at least 1 dose of study medication, and 59 completed the study. Upper limits of the 90% confidence intervals (CIs) for the difference in mean DeltaQTcF between tapentadol IR 100 or 150 mg and placebo were < 10 ms (non-inferiority criterion) for all time points. The lower limit of the 90% CI for mean DeltaQTcF between moxifloxacin and placebo exceeded 5 ms from 1 to 6 h after dosing, establishing assay sensitivity. No subject had a postdose QTc interval > 480 ms, change from baseline > 60 ms, or clinically relevant change in heart rate or other ECG variables. Steady-state concentrations were reached within 18 to 24 h. Common adverse events were vertigo (central nervous system (CNS) origin), headache, somnolence, nausea, vomiting, and feeling drunk. CONCLUSION: Therapeutic and supratherapeutic doses of tapentadol do not affect the QT/QTc interval.
Authors: Jørgen Matz; Claus Graff; Petri J Vainio; Antero Kallio; Astrid Maria Højer; Johannes J Struijk; Jørgen K Kanters; Mads P Andersen; Egon Toft Journal: Clin Drug Investig Date: 2011-11-01 Impact factor: 2.859
Authors: Nalini Vadivelu; Yili Huang; Brian Mirante; Michael Jacoby; Ferne R Braveman; Roberta L Hines; Raymond Sinatra Journal: Drug Healthc Patient Saf Date: 2013-07-03