A Study of QT and QTc Intervals in Patients Administered Extended Release Paliperidone or Quetiapine

Schizophrenia Clinical Trial

Official title: A Randomized, Double-blind, Placebo-controlled, Parallel-group Study Evaluating QT/QTc Intervals Following Administration of Extended-release Paliperidone and Quetiapine in Subjects With Schizophrenia or Schizoaffective Disorder

Status Completed

Clinical Trial Summary

The purpose of this study is to 1) determine whether the effect on QT interval corrected (QTcLD) for heart rate using the population specified linear derived method at steady state is comparable between 12 mg paliperidone extended-release (ER) once daily and that of 400-mg quetiapine administered twice daily, 2) to explore the relationship between the pharmacokinetics of paliperidone ER and electrocardiogram (ECG) parameters of interest, 3) to explore the cardiovascular safety and tolerability of 18 mg paliperidone ER at steady state, and 4) to evaluate the safety and tolerability of all treatments.

Clinical Trial Description

This multicenter, placebo- and positive-controlled, randomized study consists of 3 phases - a screening phase of up to 5 days, a 6-day placebo washout phase, and a treatment phase that includes 1-day of open-label moxifloxacin treatment (Day 1), 10 days of double-blind treatment (Days 2 to 11), and end of study evaluations (Day 12). On Day 1, all patients will receive open-label treatment with a single dose of 400 mg moxifloxacin administered in the morning. Moxifloxacin will be used to establish assay sensitivity on the QTc interval. Patients will then be randomly assigned to receive double-blind treatment with placebo, paliperidone ER, or quetiapine on Days 2 to 11. Two doses of paliperidone ER will be studied: 12 mg/day that is the maximum recommended dose and 18 mg/day that is a supratherapeutic dose (50% above the maximum recommended). Patients randomly assigned to paliperidone ER will be administered 12 mg on Days 2 to 6, 15 mg on Day 7, and 18 mg on Days 8 to 11. Patients randomly assigned to quetiapine will receive 100 mg bid on Day 2, 200 mg twice daily (bid) on Day 3, 300 mg bid on Day 4, and 400 mg bid on Days 5 to 11. Patients will receive double-blind study drug 30 minutes after having a standardized breakfast on Days 2 to 11. Serial time matched 12 lead ECG triplicate readings will be recorded on Days -2, -1, 6, and 11 (predose and 1, 1.5, 2.5, 3.5, 4.5, 6, and 12 hours postdose) as well as Day 1 (predose, 1, 1.5, 2.5, 3.5 hours postdose) and Days 7 and 12 (23.5 hours postdose). This study will explore the QTc and pharmacokinetic data from paliperidone ER (commercial formulation) and quetiapine (marketed atypical antipsychotic of the same therapeutic class) at the maximum recommended doses for both products and at a supratherapeutic dose (50% above the maximum proposed labeled dose) for paliperidone ER. Safety and tolerability will be monitored throughout the study.

A single oral dose of moxifloxacin 400 mg tablet on Day 1; Oral paliperidone ER 12 mg on Days 2 to 6; 15 mg on Day 7, and 18 mg on Days 8 to 11; Oral quetiapine 100 mg twice daily (bid) on Day 2; 200 mg bid on Day 3; 300 mg bid on Day 4; and 400 mg bid on Days 5 to 11. ;

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Psychotic Disorders
• Schizoaffective Disorder
• Schizophrenia

• NCT number: NCT00791622
• Study type: Interventional
• Source: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• Status: Completed
• Phase: Phase 1
• Start date: January 2006
• Completion date: June 2006