Evaluation of the effect of paliperidone extended release and quetiapine on corrected QT intervals: a randomized, double-blind, placebo-controlled study.
The effect of two atypical antipsychotics on QTc intervals (heart rate-corrected QT interval) was evaluated. Patients (N=109) with schizophrenia (79%) or schizoaffective disorder (21%) were randomly assigned in 2 : 2 : 1 ratio to paliperidone extended release (ER), quetiapine, or placebo. Doses of 12 and 18 mg/day of paliperidone ER were compared with quetiapine 800 mg/day. Least-squares mean change from baseline in population-specific linear-derived correction method from baseline to days 6-7 at individual tmax was 5.1 ms less [90% confidence interval: -9.2 to -0.9] with paliperidone ER 12 mg/day than with quetiapine 800 mg/day. On the basis of a prespecified 10-ms noninferiority margin, paliperidone ER was thus declared noninferior to quetiapine (primary analysis). Mean change in population-specific linear-derived correction method from baseline to days 11-12 at individual tmax was 2.3 ms less (90% confidence interval: -6.8 to 2.3) with paliperidone ER 18 mg/day than with quetiapine 800 mg/day. Treatment-emergent adverse events occurred in 36 (82%) patients treated with paliperidone ER, 41 (95%) patients treated with quetiapine, and 14 (64%) patients treated with placebo. No adverse events of a proarrhythmic nature were noted. The effect on the QTc interval in patients with schizophrenia or schizoaffective disorder was comparable between paliperidone ER 12 mg/day (maximum recommended dose), paliperidone ER 18 mg/day (supratherapeutic dose), and quetiapine 800 mg/day.
Hough
David W
DW
aJohnson & Johnson Pharmaceutical Research & Development, L.L.C., Raritan, New Jersey, USA bJohnson & Johnson Pharmaceutical Research & Development, Division of Janssen Pharmaceutica N.V., Beerse, Belgium.
Natarajan
Jaya
J
Vandebosch
An
A
Rossenu
Stefan
S
Kramer
Michelle
M
Eerdekens
Mariëlle
M
D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects*; D003692:Delayed-Action Preparations; D003987:Dibenzothiazepines / Q000494:pharmacology* / Q000627:therapeutic use; D004311:Double-Blind Method; D004562:Electrocardiography; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000494:pharmacology* / Q000627:therapeutic use; D008133:Long QT Syndrome / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D000068882:Paliperidone Palmitate; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use; D000069348:Quetiapine Fumarate; D012559:Schizophrenia / Q000188:drug therapy; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D003987:Dibenzothiazepines; D007555:Isoxazoles; D011743:Pyrimidines; D000069348:Quetiapine Fumarate; D000068882:Paliperidone Palmitate