SchizophreniaPhase 3NCT00216476
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
A Phase 3 study testing Aripiprazole, Risperidone Long Acting Injectable (LAI) and Quetiapine in people with Schizophrenia and Psychotic Disorders, run by Janssen-Cilag International NV at 96 sites in 24 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Schizophrenia, Psychotic Disorders
- What is being tested?
- Aripiprazole, Risperidone Long Acting Injectable (LAI) and Quetiapine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 753 participants
- Where
- 96 sitesin 24 countries
- Study dates
- Oct 2004to Nov 2007
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
96 sites in 24 countries.
96 sites in 24 countries
France10 sites
Study site
Bron
Study site
Brumath
Study site
Créteil
Study site
Dieppe
Study site
Hénin-Beaumont
Study site
Mont-Saint-Martin
Study site
Poitiers
Study site
Reims
Study site
Roubaix
Study site
Toulouse
Germany10 sites
Study site
Augsburg
Study site
Berlin
Study site
Bochum
Study site
Duisburg
Study site
Düsseldorf
Study site
Karlstadt am Main
Study site
Krefeld
Study site
München
Study site
Oranienburg
Study site
Stralsund
Czechia9 sites
Study site
Brno
Study site
Lnáře
Study site
Opava
Study site
Pardubice
Study site
Plzen Czechia
Study site
Prague
Study site
Praha 2 N/A
Study site
Uherský Brod
Study site
Ústí nad Labem
Hungary6 sites
Study site
Budapest
Study site
Gyõr
Study site
Gyula
Study site
Kistarcsa
Study site
Szeged
Study site
Vác
Lithuania5 sites
Study site
Alytus
Study site
Kaunas
Study site
Klaipėda
Study site
Šiauliai
Study site
Vilnius
United Kingdom5 sites
Study site
Barnet
Study site
Barnsley
Study site
Hull
Study site
Llantrissant
Study site
Swansea
Croatia4 sites
Study site
Osijek
Study site
Rijeka
Study site
Split
Study site
Zagreb
Ireland4 sites
Study site
Cork
Study site
Dublin
Study site
Kerry
Study site
Sligo
Poland4 sites
Study site
Choroszcz
Study site
Gdynia Na
Study site
Poznan
Study site
Warsaw
Spain4 sites
Study site
Madrid
Study site
Oviedo (Asturias)
Study site
Seville
Study site
Valencia
Turkey (Türkiye)4 sites
Study site
Ankara Turkey
Study site
Bakirkoy/Istanbul N/A
Study site
Istanbul
Study site
Izmir
Slovenia3 sites
Study site
Begunje na Gorenjskem
Study site
Ljubljana
Study site
Ormoz
About this study
Official title: CONSTATRE: Risperdal Consta Trial Of Relapse Prevention And Effectiveness
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.
Read the 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.
- Conditions
- Schizophrenia, Psychotic Disorders
- Being tested
- Aripiprazole, Risperidone Long Acting Injectable (LAI), Quetiapine
- Keywords
- Schizophrenia, relapse prevention, Antipsychotic agents, Long-acting risperidone, Quetiapine, Aripiprazole
- Medical subject headings
- Schizophrenia, Psychotic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AripiprazoleDrug
10-30 mg oral once daily for 104 weeks
Risperidone Long Acting Injectable (LAI)Drug
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.
QuetiapineDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 001 | Experimental | 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. Receives: Drug: Risperidone Long Acting Injectable (LAI) |
| 002 | Active comparator | 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. Receives: Drug: Quetiapine |
| 003 | Other | Aripiprazole 10-30 mg oral once daily for 104 weeks Receives: Drug: Aripiprazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Relapse Free Period(Risperidone LAI Versus 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. The relapse rate in each treatment arm was estimated using the Kaplan-Meier method.
Measured: 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)
Secondary outcomes (4)
Mean Relapse Free Period (Exploratory/Aripiprazole)
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.
Measured: 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)
Change From Baseline to Endpoint in Total Positive and Negative Syndrome Scale (PANSS) Score
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).
Measured: 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)
Change From Baseline to Endpoint in Clinical Global Impression Scale (CGI) Score
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).
Measured: 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)
Change From Baseline to Endpoint in Short-Form Health Survey 12 (SF-12) Scores
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.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2005 (estimated)
- Study startOct 2004
- Primary completionNov 2007
- Study completionNov 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 753 participants (actual)
Sponsor and investigators
- Lead sponsor
- Janssen-Cilag International NV
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Janssen-Cilag International NV Clinical Trial, Study director, Janssen-Cilag International NV
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00216476
- Sponsor's protocol ID
- CR002269
- Status last verified
- Mar 2014
- First submitted
- 13 Sep 2005
- Last updated
- 16 Apr 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CONSTATRE: Risperdal Consta Trial Of Relapse Prevention And Effectiveness
- ClinicalTrials.gov ID
- NCT00216476
- Acronym / sponsor ID
- CR002269
- Conditions
- Schizophrenia, Psychotic Disorders
- Keywords
- Schizophrenia, relapse prevention, Antipsychotic agents, Long-acting risperidone, Quetiapine, Aripiprazole
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 753 participants (actual)
- Lead sponsor
- Janssen-Cilag International NVIndustry (pharma, biotech, devices)
- Study start
- Oct 2004
- Primary completion
- Nov 2007 (actual)
- Study completion
- Nov 2007 (actual)
- First posted
- 22 Sep 2005 (estimated)
- Results
- Posted 10 Aug 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 001 | Experimental | Drug: Risperidone Long Acting Injectable (LAI)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. |
| 002 | Active comparator | Drug: QuetiapineQuetiapine 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 | Other | Drug: AripiprazoleAripiprazole 10-30 mg oral once daily for 104 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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)
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Aripiprazole10-30 mg oral once daily for 104 weeks | Drug | 003 |
| 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 | 001 |
| QuetiapineOral 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 | 002 |
Primary outcome
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)
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.
4 secondary outcomes
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)
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)
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)
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Apr 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- CONSTATRE: Risperdal� Consta� Trial of Relapse Prevention and Effectiveness RIS-SCH-3001 Study Results SynopsisLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Janssen-Cilag International NV Clinical Trial study director
Janssen-Cilag International NV
96 sites in 24 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Aripiprazole, Risperidone Long Acting Injectable (LAI) and Quetiapine in people with Schizophrenia and Psychotic Disorders, run by Janssen-Cilag International NV at 96 sites in 24 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 96 sites in France, Germany, Czechia, Hungary, Lithuania and 19 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Aug 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Apr 2014.