Back to resultsA Study of QT and QTc Intervals in Patients Administered Extended Release Paliperidone or Quetiapine
Primary Purpose
Schizophrenia, Schizoaffective Disorder
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Paliperidone ER
Sponsored by
About this trial
This is an interventional treatment trial for Schizophrenia focused on measuring Paliperidone ER, Schizophernia, Mood Disorders, Antipsychotic drugs, Cardiovascular, Schizoaffective Disorder
Eligibility 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
Sites / Locations
Outcomes
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
Full Information
NCT ID
NCT00791622
First Posted
November 13, 2008
Last Updated
May 17, 2011
Sponsor
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
1. Study Identification
Unique Protocol Identification Number
NCT00791622
Brief Title
A Study of QT and QTc Intervals in Patients Administered Extended Release Paliperidone or Quetiapine
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2010
Overall Recruitment Status
Completed
Study Start Date
January 2006 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
June 2006 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
4. Oversight
5. Study Description
Brief 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia, Schizoaffective Disorder
Keywords
Paliperidone ER, Schizophernia, Mood Disorders, Antipsychotic drugs, Cardiovascular, Schizoaffective Disorder
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
Double
Allocation
Randomized
Enrollment
110 (Actual)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
Paliperidone ER
Primary Outcome Measure Information:
Title
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 Measure Information:
Title
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Johnson & Johnson Pharmaceutical Research and Development, L.L.C. Clinical Trial
Organizational Affiliation
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Official's Role
Study Director
12. IPD Sharing Statement
Links:
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_JNJ_6051&studyid=725&filename=CR011056_CSR.pdf
Description
A study of QT and QTc intervals in patients administered extended release paliperidone or quetiapine
Learn more about this trial
A Study of QT and QTc Intervals in Patients Administered Extended Release Paliperidone or Quetiapine
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