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

This study has been completed.
Sponsor:
Information provided by:
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:
NCT00791622
First received: November 13, 2008
Last updated: May 17, 2011
Last verified: April 2010
  Purpose

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.


Condition Intervention Phase
Schizophrenia
Schizoaffective Disorder
Drug: Paliperidone ER
Phase 1

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

Resource links provided by NLM:


Further study details as provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:

Primary Outcome Measures:
  • To determine whether the effect on QTcLD is comparable between 12-mg paliperidone ER at steady state and that of 400-mg quetiapine at steady state with twice daily dose administration.

Secondary Outcome Measures:
  • To explore the relationship between the pharmacokinetics of paliperidone ER and ECG parameters of interest, to evaluate the cardiovascular safety and tolerability of 18-mg paliperidone ER at steady state, and to evaluate overall safety and tolerability

Enrollment: 110
Study Start Date: January 2006
Study Completion Date: June 2006
Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of schizophrenia or schizoaffective disorder as defined by DSM-IV-TR criteria, with stable symptoms. Symptom stability is based on the clinical judgment of the investigator but should include as a minimum: no exacerbation of psychotic symptoms or psychiatric hospitalization for at least 3 months before screening and a CGI-S score of < =4 (moderate) at screening and Day -1
  • Must have a normal 12-lead ECG at screening and on Days -1 and -2, including: Normal sinus rhythm (heart rate between 50 and 100 beats per minute
  • QTcB interval < = 430 milliseconds for men, < = 450 milliseconds for women
  • QRS interval < 110 milliseconds
  • PR interval < 200 milliseconds
  • Must weigh > = 50 kg ( > = 110 lb), with a BMI > = 18 and < = 35 kg/m2
  • If female, must be postmenopausal for at least 2 years, surgically sterile, abstinent, or agree to practice an effective method of birth control if they are sexually active before entry and throughout the study. Effective methods of birth control include: abstinence, prescription oral contraceptives, contraceptive injections, intrauterine device, double barrier method, contraceptive patch, and male partner sterilization. Women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline before receiving a dose of study drug

Exclusion Criteria:

  • Meets DSM-IV criteria for substance dependence in the 3 months before screening
  • Is at risk for suicidal or violent behavior, as judged by the investigator
  • Has a clinically significant abnormality on ECG at screening or on Days 2 and -1 of the study
  • Has a heart rhythm disturbance that is known or suggested by history or that is demonstrated on ECG at screening, or on Days -2 and -1 of the study
  • Has a blood pressure outside of the normal range (supine systolic blood pressure < 90 or > 140 mmHg or diastolic blood pressure < 60 or > 90 mmHg)
  • Has unusual T-wave morphology in a majority of leads of the ECG (such as bifid T waves, low T waves) or prominent U waves at screening
  • Has a history of additional risk factors for torsade de pointes, such as heart failure, hypokalemia, family history of known short or long QT syndrome, or sudden unexplained death at a young age (< = 40 years) in a first-degree relative (i.e., biological parent, sibling, or offspring)
  • Has a relevant history of any significant and/or unstable cardiovascular, respiratory (including bronchial asthma), neurologic (including seizures or significant cerebrovascular disease), renal, hepatic, endocrine, immunologic, ophthalmologic, hematologic, or other systemic disease
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00791622

Sponsors and Collaborators
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Investigators
Study Director: Johnson & Johnson Pharmaceutical Research and Development, L.L.C. Clinical Trial Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00791622     History of Changes
Other Study ID Numbers: CR011056
Study First Received: November 13, 2008
Last Updated: May 17, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:
Paliperidone ER
Schizophernia
Mood Disorders, Antipsychotic drugs
Cardiovascular
Schizoaffective Disorder

Additional relevant MeSH terms:
Schizophrenia
Disease
Psychotic Disorders
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Pathologic Processes
9-hydroxy-risperidone
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs

ClinicalTrials.gov processed this record on October 02, 2014