Clinical trial NCT00216476: 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
Official title: CONSTATRE: Risperdal Consta Trial Of Relapse Prevention And Effectiveness
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Schizophrenia
Psychotic Disorders
Keywords: Schizophrenia, relapse prevention
Antipsychotic agents
Long-acting risperidone
Quetiapine
Aripiprazole
Lead sponsor: Janssen-Cilag International NV
Sponsor class: INDUSTRY
First posted: 2005-09-22
Enrollment: 753
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: Mean Relapse Free Period(Risperidone LAI Versus Quetiapine)
timeFrame: 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:
measure: Mean Relapse Free Period (Exploratory/Aripiprazole)
timeFrame: 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)
measure: Change From Baseline to Endpoint in Total Positive and Negative Syndrome Scale (PANSS) Score
timeFrame: 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)
measure: Change From Baseline to Endpoint in Clinical Global Impression Scale (CGI) Score
timeFrame: 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)
measure: Change From Baseline to Endpoint in Short-Form Health Survey 12 (SF-12) Scores
timeFrame: 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
Other outcomes:
Locations:
city: Hall In Tirol
country: Austria
city: Linz
country: Austria
city: Neunkirchen
country: Austria
city: Pleven
country: Bulgaria
city: Sofia Sofia
country: Bulgaria
city: Sofia
country: Bulgaria
city: Osijek
country: Croatia
city: Rijeka
country: Croatia
city: Split
country: Croatia
city: Zagreb
country: Croatia
city: Brno
country: Czech Republic
city: Lnare
country: Czech Republic
city: Opava N/A
country: Czech Republic
city: Pardubice
country: Czech Republic
city: Plzen Czechia
country: Czech Republic
city: Praha 2 N/A
country: Czech Republic
city: Praha 8
country: Czech Republic
city: Uhersky Brod
country: Czech Republic
city: Usti Nad Labem N/A
country: Czech Republic
city: Middelfart N/A
country: Denmark
city: Vordingborg N/A
country: Denmark
city: Pÿrnu N/A
country: Estonia
city: Tallinn N/A
country: Estonia
city: Tartu N/A
country: Estonia
city: Bron N/A
country: France
city: Brumath Cedex
country: France
city: Creteil
country: France
city: Dieppe N/A
country: France
city: Henin Beaumont
country: France
city: Mont St Martin
country: France
city: Poitiers N/A
country: France
city: Reims
country: France
city: Roubaix
country: France
city: Toulouse N/A
country: France
city: Augsburg
country: Germany
city: Berlin
country: Germany
city: Bochum
country: Germany
city: Duisburg
country: Germany
city: Düsseldorf
country: Germany
city: Karlstadt
country: Germany
city: Krefeld
country: Germany
city: München
country: Germany
city: Oranienburg
country: Germany
city: Stralsund
country: Germany
city: Heraklion -Crete
country: Greece
city: Thessalonikis
country: Greece
city: Budapest N/A
country: Hungary
city: Budapest
country: Hungary
city: Gyula
country: Hungary
city: Gyõr
country: Hungary
city: Kistarcsa
country: Hungary
city: Szeged N/A
country: Hungary
city: Vac N/A
country: Hungary
city: Cork
country: Ireland
city: Dublin N/A
country: Ireland
city: Kerry
country: Ireland
city: Sligo N/A
country: Ireland
city: Jerusalem
country: Israel
city: Ramat-Gan
country: Israel
city: Tel Aviv
country: Israel
city: Jelgava
country: Latvia
city: Riga
country: Latvia
city: Alytus
country: Lithuania
city: Kaunas
country: Lithuania
city: Klaipeda
country: Lithuania
city: Siauliai
country: Lithuania
city: Vilnius
country: Lithuania
city: Choroszcz
country: Poland
city: Gdynia Na
country: Poland
city: Poznan
country: Poland
city: Warszawa
country: Poland
city: Coimbra
country: Portugal
city: Porto N/A
country: Portugal
city: Bucharest
country: Romania
city: Bucuresti
country: Romania
city: Craiova
country: Romania
city: Iasi
country: Romania
city: Al Khobar
country: Saudi Arabia
city: Kosice
country: Slovakia
city: Zvolen
country: Slovakia
city: Begunje
country: Slovenia
city: Ljubljana
country: Slovenia
city: Ormoz
country: Slovenia
city: Madrid
country: Spain
city: Oviedo (Asturias)
country: Spain
city: Sevilla N/A
country: Spain
city: Valencia N/A
country: Spain
city: Göteborg
country: Sweden
city: Trollhättan
country: Sweden
city: Ankara Turkey
country: Turkey
city: Bakirkoy/Istanbul N/A
country: Turkey
city: Istanbul
country: Turkey
city: Izmir
country: Turkey
city: Barnet
country: United Kingdom
city: Barnsley
country: United Kingdom
city: Hull
country: United Kingdom
city: Llantrissant
country: United Kingdom
city: Swansea
country: United Kingdom
Study officials:
affiliation: Janssen-Cilag International NV
name: Janssen-Cilag International NV Clinical Trial
role: STUDY_DIRECTOR
References: