A Study of Relapse Prevention and the Effectiveness of Long-acting Injectable Risperidone and Quetiapine Tablets in the Treatment of Patients With Schizophrenia or Schizoaffective Disorder

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen-Cilag International NV
ClinicalTrials.gov Identifier:
NCT00216476
First received: September 13, 2005
Last updated: March 25, 2014
Last verified: March 2014
  Purpose

The purpose of this study is to investigate whether a long-acting injectable formulation of risperidone provides better effectiveness over 2 years, as measured by the time to relapse, compared with quetiapine tablets in a routine psychiatric care setting. Aripiprazole will be investigated in a descriptive manner.


Condition Intervention Phase
Schizophrenia
Psychotic Disorders
Drug: Aripiprazole
Drug: Risperidone Long Acting Injectable (LAI)
Drug: Quetiapine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: CONSTATRE: Risperdal Consta Trial Of Relapse Prevention And Effectiveness

Resource links provided by NLM:


Further study details as provided by Janssen-Cilag International NV:

Primary Outcome Measures:
  • Mean Relapse Free Period(Risperidone LAI Versus Quetiapine) [ Time Frame: Assessed at each visit from the moment the subject was randomized to a treatment arm (baseline visit) until the end of treatment (Week 104 or earlier) ] [ Designated as safety issue: No ]
    Relapse was defined as meeting any of the predefined criteria (adapted from Csernansky et al., 2002) on 2 consecutive evaluations during treatment, 3 to 5 days apart. The relapse rate in each treatment arm was estimated using the Kaplan-Meier method.


Secondary Outcome Measures:
  • Mean Relapse Free Period (Exploratory/Aripiprazole) [ Time Frame: Assessed at each visit from the moment the subject was randomized to a treatment arm (baseline visit) until the end of treatment (Week 104 or earlier) ] [ Designated as safety issue: No ]
    As for risperidone and quetiapine, relapse was defined as meeting any of the predefined criteria (adapted from Csernansky et al., 2002) on 2 consecutive evaluations during treatment, 3 to 5 days apart. Since aripiprazole was new on the market at the time the study was conducted, this aripiprazole analysis was exploratory.

  • Change From Baseline to Endpoint in Total Positive and Negative Syndrome Scale (PANSS) Score [ Time Frame: Assessed at each visit from the moment the subject was randomized to a treatment arm (baseline visit) until the end of treatment (Week 104 or earlier) ] [ Designated as safety issue: No ]

    The neuropsychiatric symptoms of schizophrenia were assessed by means of the 30-item PANSS scale. The PANSS scale provides a total score (sum of the scores of all 30 items) and scores for 3 subscales, i.e., the positive subscale (7 items), the negative subscale (7 items), and the general psychopathology subscale (16 items).

    Each item of the scale is to be scored on a scale of 1 (absent) to 7 (extreme).


  • Change From Baseline to Endpoint in Clinical Global Impression Scale (CGI) Score [ Time Frame: Assessed at each visit from the moment the subject was randomized to a treatment arm (baseline visit) until the end of treatment (Month 24 or earlier) ] [ Designated as safety issue: No ]
    The 7-point CGI scale of Severity (CGI-S) was used to assess the severity of a subject's psychotic condition (0= normal, not at all ill, 1= borderline, etc. and 6= among the most extremely ill subjects).

  • Change From Baseline to Endpoint in Short-Form Health Survey 12 (SF-12) Scores [ Time Frame: Assessed at the moment the subject was randomized to a treatment arm (baseline visit) and after 1, 3, 6, 12, 18, and 24 months of treatment ] [ Designated as safety issue: No ]
    Quality of life was assessed by means of the 12-item SF-12® survey. Two parameters, i.e., PCS (physical component summary) and MCS (mental component summary) were calculated. Both components scores range from 0 to 100 with higher scores indicating better QOL.


Enrollment: 753
Study Start Date: October 2004
Study Completion Date: November 2007
Primary Completion Date: November 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 001
Risperidone Long Acting Injectable (LAI) 25 mg injection every 2 weeks until week 104. Dosage may be increased or decreased in steps of 12.5 mg. Additional oral risperidone can be administered as required until a dose increase becomes effective.
Drug: Risperidone Long Acting Injectable (LAI)
25 mg injection every 2 weeks until week 104. Dosage may be increased or decreased in steps of 12.5 mg. Additional oral risperidone can be administered as required until a dose increase becomes effective.
Active Comparator: 002
Quetiapine Oral tablets are titrated from 50 mg daily to 300-400 mg daily in first 4 days. Subsequently treatment is maintained for 104 weeks and dosage can be adjusted with increments or decrements of 25 to 50 mg.
Drug: Quetiapine
Oral tablets are titrated from 50 mg daily to 300-400 mg daily in first 4 days. Subsequently treatment is maintained for 104 weeks and dosage can be adjusted with increments or decrements of 25 to 50 mg.
003
Aripiprazole 10-30 mg oral once daily for 104 weeks
Drug: Aripiprazole
10-30 mg oral once daily for 104 weeks

Detailed Description:

Although many schizophrenia patients currently take oral antipsychotic medications, it is estimated that up to 75% of them have difficulty adhering to the daily oral regimen. Long-acting injectable formulations may eliminate the need for daily medication and enhance patient compliance with the treatment regimen. This is an open-label (all people involved know the identity of the intervention), randomized (study drug assigned by chance) study of a formulation of risperidone (coated microspheres) injected into the muscle at 2 week intervals over 104 weeks in stable patients with schizophrenia or schizoaffective disorder, who are being treated with oral risperidone, olanzapine, or other conventional antipsychotic agents. A comparator group will receive tablets of quetiapine to be taken 2 or 3 times daily, depending on the optimal dosage. In countries where aripiprazole is available, aripiprazole was also included in a descriptive manner. Reasons for switching symptomatically stable patients from their current antipsychotic treatment include insufficient effectiveness of the medication on symptoms, adverse events, or a patient's request. The principal measure of effectiveness of the drug is the time to relapse. Assessments of effectiveness also include: Positive and Negative Syndrome Scale (PANSS), which measures the symptoms of schizophrenia; overall severity of illness measured by the Clinical Global Impression subscale (CGI-S); patient's condition measured by the Clinical Global Impression condition subscale (CGI-C); quality of life assessed by the SF-12 survey. Safety evaluations include incidence of adverse events, Extrapyramidal Symptoms Rating Scale (ESRS), clinical laboratory tests (biochemistry, haematology, and urinalysis), and vital signs (pulse, blood pressure). The study hypothesis is that treatment with long-acting risperidone injected intramuscularly every 2 weeks provides better effectiveness than quetiapine, as measured by time to relapse, in patients with schizophrenia or schizoaffective disorder. Risperidone injections 25mg biweekly for 104 weeks, increasing or decreasing (increments of 12.5mg) at investigator's discretion. Risperidone tablets (2mg daily for 2 days) for patients starting on risperidone. Quetiapine and Aripiprazole used according to package insert.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of schizophrenia or schizoaffective disorder according to the Diagnostic and Statistical Manual of Mental Diseases, 4th edition (DSM-IV)
  • Patients currently treated with oral risperidone, olanzapine or a conventional neuroleptic monotherapy at doses not exceeding 6 mg risperdal, 20 mg olanzapine, or a conversion dose of 10 mg haloperidol for oral conventional agents
  • Patients who are stable (judged clinically stable by the investigator and on a stable dose of medication for 4 weeks or longer) but not optimally treated (non-satisfactory treatment regarding symptoms or adverse events)

Exclusion Criteria:

  • Diagnosis other than schizophrenia or schizoaffective disorder by DSM-IV Axis I criteria
  • Patients being treated with antipsychotic agents other than oral risperidone, olanzapine or conventional oral neuroleptic agents
  • Patients with known hypersensitivity to oral risperidone, quetiapine, aripiprazole, or who are known non-responders to oral risperidone, quetiapine, aripiprazole or to previous treatment with at least 2 antipsychotic agents
  • Patients treated with mood stabilizers or antidepressants who are not on stable dose for at least 3 months before study initiation
  • Pregnant or nursing females, or those lacking adequate contraception
  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: NCT00216476

  Show 98 Study Locations
Sponsors and Collaborators
Janssen-Cilag International NV
Investigators
Study Director: Janssen-Cilag International NV Clinical Trial Janssen-Cilag International NV
  More Information

Additional Information:
No publications provided

Responsible Party: Janssen-Cilag International NV
ClinicalTrials.gov Identifier: NCT00216476     History of Changes
Other Study ID Numbers: CR002269
Study First Received: September 13, 2005
Results First Received: July 8, 2010
Last Updated: March 25, 2014
Health Authority: Belgium: Ministry of Social Affairs, Public Health and the Environment
Germany: Ethics Commission

Keywords provided by Janssen-Cilag International NV:
Schizophrenia, relapse prevention
Antipsychotic agents
Long-acting risperidone
Quetiapine
Aripiprazole

Additional relevant MeSH terms:
Psychotic Disorders
Mental Disorders
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Antipsychotic Agents
Risperidone
Quetiapine
Aripiprazole
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Dopamine Antagonists
Dopamine Agents

ClinicalTrials.gov processed this record on July 22, 2014