Comparison of the Subjective Well-being and Tolerability of Quetiapine XR to Risperidone

Study Overview
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Brief Summary
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The trial is designed to assess the long term subjective well-being in schizophrenic outpatients treated with quetiapine XR (extended release) or oral risperidone at flexible dose in a naturalistic setting over a period of one year. Secondary outcome measures have been selected for helping in the differentiation of the compared atypical antipsychotics. The primary objective of this study is to demonstrate the non-inferiority of quetiapine XR to risperidone assessed at month 6 in terms of responder rate using the self-report instrument SWN-K

Official Title
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A One-Year Randomized, Prospective, Parallel, Open Comparison of Subjective Well-being in Schizophrenic Out-patients Treated With Quetiapine XR (SEROQUEL XR™) or Oral Risperidone at Flexible Dose in a Naturalistic Setting

Conditions
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Schizophrenic Disorders

Intervention / Treatment
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* Drug: Quetiapine XR
* Drug: Risperidone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Treated for symptomatic schizophrenia (DSM-IV-TR codes: 295.10, 295.20, 295.30,295.60, 295.90) or schizoaffective disorder (DSM-IV-TR code:295.70) or schizophreniform disorder (DSM-IV-TR code: 295.40). Patients with co-morbid depressive symptoms may be enrolled Patient with first episode of the above mentioned disease (item 3) or patient requiring a medication change for clinical reasons (effectiveness, tolerability, compliance, patient preference), i.e. switch from typical to atypical neuroleptics, switch from other atypical neuroleptics, excluding patients treated with risperidone or quetiapine at the time of enrolment. Exclusion Criteria: Patients with a baseline SWN-K total score of >75 Patients with previous treatment with risperidone or quetiapine may be enrolled if change of treatment has not been dictated by major lack of tolerability and efficacy and if date of last dose has been at least 3 months prior to enrolment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Quetiapine XR<br> | Drug: Quetiapine XR<br>* Oral, once daily, tablets of 400 mg to 800 mg<br>* Other names: Seroquel XR;|
| Active Comparator: Risperidone<br> | Drug: Risperidone<br>* Oral, once daily, tablets of 2 mg to 6 mg<br>* Other names: Risperdal;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Responder Rate at Month 6 in the Per Protocol Population Using the Subjective Well-being Under Neuroleptics Scale, Short Version (SWN-K) Total Score | The SWN-K is comprised of 20 questions, rated on a 6-point scale from 1 (not at all) to 6 (very much). Scores range from 20 to 120, with higher scores implying higher subjective well-being. A responder is defined as a subject with an increase of 10 points or 20% from baseline in SWN-K total score (non-inferiority limit of -9.7% in responder rate) | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean Subjective Well-Being Under Neuroleptic Treatment Scale (SWN-K) Total Score at Month 12 in the Per Protocol Population | The SWN-K is comprised of 20 questions, each of which is rated using a 6-point scale ranging from 1 (not at all) to 6 (very much). Possible scores range from 20 to 120, with higher scores implying higher subjective well-being. | Baseline and Month 12 | 
| Change From Baseline in Mean Subjective Well-Being Under Neuroleptic Treatment Scale (SWN-K) Total Score at Month 12 in the Intent-to-Treat (ITT) Population | The SWN-K is comprised of 20 questions, each of which is rated using a 6-point scale ranging from 1 (not at all) to 6 (very much). Possible scores range from 20 to 120, with higher scores implying higher subjective well-being. | Baseline and Month 12 | 
| Change From Baseline in the Subjective Well-Being Under Neuroleptic Treatment Scale (SWN-K) Subscale Score: Physical Functioning at Month 12 in the ITT Population. | The SWN-K total score is the sum of 5 subscores (4 questions each): physical functioning, social integration, mental functioning, self-control, and emotional regulation. The subscores are rated using a 6-point scale (the higher the grade, the better the response). Possible subscores range from 4 to 24. | Baseline and 12 months | 
| Change From Baseline in the Subjective Well-Being Under Neuroleptic Treatment Scale (SWN-K) Subscale Score: Social Integration at Month 12 in the ITT Population. | The SWN-K total score is the sum of 5 subscores (4 questions each): physical functioning, social integration, mental functioning, self-control, and emotional regulation. The subscores are rated using a 6-point scale (the higher the grade, the better the response). Possible subscores range from 4 to 24. | Baseline and 12 months | 
| Change From Baseline in the Subjective Well-Being Under Neuroleptic Treatment Scale (SWN-K) Subscale Score: Mental Functioning at Month 12 in the ITT Population. | The SWN-K total score is the sum of 5 subscores (4 questions each): physical functioning, social integration, mental functioning, self-control, and emotional regulation. The subscores are rated using a 6-point scale (the higher the grade, the better the response). Possible subscores range from 4 to 24. | Baseline and 12 months | 
| Change From Baseline in the Subjective Well-Being Under Neuroleptic Treatment Scale (SWN-K) Subscale Score: Self-control at Month 12 in the ITT Population. | The SWN-K total score is the sum of 5 subscores (4 questions each): physical functioning, social integration, mental functioning, self-control, and emotional regulation. The subscores are rated using a 6-point scale (the higher the grade, the better the response). Possible subscores range from 4 to 24. | Baseline and 12 months | 
| Change From Baseline in the Subjective Well-Being Under Neuroleptic Treatment Scale (SWN-K) Subscale Score: Emotional Regulation at Month 12 in the ITT Population. | The SWN-K total score is the sum of 5 subscores (4 questions each): physical functioning, social integration, mental functioning, self-control, and emotional regulation. The subscores are rated using a 6-point scale (the higher the grade, the better the response). Possible subscores range from 4 to 24. | Baseline and 12 months | 
| The Remission Rate in Both the Quetiapine XR Group and the Risperidone Group at Month 12 in the ITT Population | Remission was defined as a SWN-K total score greater than or equal to 80. The reported population is participants who showed remission over, time from baseline to Month 12 | 12 months | 
| The Effect of Quetiapine XR Versus Risperidone at Month 12 in the ITT Population on Core Schizophrenic and Depressive Symptoms by Evaluating the Change From Baseline in CGI-SCH Overall Severity Score (Improved). | For the CGI-SCH overall severity of illness, the score ranged from 1 (normal, not ill) to 7 (among the most severely ill). CGI-SCH score was divided into 3 classes: worsening (change score>0), stable (change score=0) and improved (change score<0). Change from baseline in CGI-SCH overall severity of illness in number of participants with CGI-SCH overall severity score improvement. | 12 months | 
| The Effect of Quetiapine XR Versus Risperidone at Month 12 in the ITT Population on Core Schizophrenic and Depressive Symptoms by Evaluating the Change From Baseline in CGI-SCH Overall Severity Score | For the CGI-SCH (Clinical Global Impression-Schizophrenia severity of illness scale) overall severity of illness, the score ranged from 1 (normal, not ill) to 7 (among the most severely ill). Change from baseline in CGI-SCH score was divided into 3 classes: worsening (change score>0), stable (change score=0) and improved (change score<0). | 12 months | 
| The Effect of Quetiapine XR Versus Risperidone at Month 12 in the ITT Population on Core Schizophrenic and Depressive Symptoms by Evaluating the Change From Baseline in the Calgary Depression Scale for Schizophrenia (CDSS) Total Score | The CDSS total score is the sum of 9 questions and ranges from 0 to 27. The higher the score, the more severe are the symptoms. | 12 months | 
| The Effect of Quetiapine XR Versus Risperidone by Evaluating the Relapse Rate at Month 12 in the ITT Population | Relapse is defined as at least one increase of greater than or equal to 2 points on the CGI-SCH overall severity score during the treatment period or at least one hospitalization due to psychiatric disorders during the treatment period. | 12 months | 
| Evaluation of Effect of Quetiapine XR Versus Risperidone on the Health-related Quality of Life of Patients With Schizophrenia by Evaluating the Change From Baseline in EQ-5D(Euro Quality of Life-5 Dimension) Index Score at Month 12 in the ITT Population. | The Euro Quality of Life - 5 dimension index (EQ-5D) is the result of the application of a formula that essentially attaches values (also called weights) to each of the levels (no, some, or heavy problems) in each dimension (mobility, self-care, usual activities, pain/discomfort, anxiety/depression). These weights are issued from a representative sample of the general population. The total possible maximum value was 1 (healthy life) and the minimum value was 0 (death). | 12 months | 
| To Evaluate the Effect of Quetiapine XR Versus Risperidone at Month 12 in the ITT Population Regarding Health Economics Outcomes by Evaluating the Functional Improvement Rate of the Modified Vocational Status Index/ Location Code Index: Stable State | Stable State was defined as having the same status in occupational and residential status as at Baseline. | 12 months | 
| The Effect of Quetiapine XR Versus Risperidone Regarding Health Economics Outcomes by Evaluating the Mean Number of Lost School/Work Days at Month 12 in the ITT Population | Workers and students are defined from the modified vocational status index excluding subjects Retired or Unemployed, whether or not expected to work. | 12 months | 
| The Effect of Quetiapine XR Versus Risperidone Regarding Health Economics Outcomes by Evaluating the Participants With at Least 1 Hospitalization Due to Psychiatric Disorders at Month 12 in the ITT Population | All hospitalizations due to psychiatric disorders during the study (i.e. from Visit 1 to Termination date + 30 days) in inpatients units, in emergency wards, and in day clinics. | 12 months | 
| Number of Subjects Who Had an Unscheduled Visits Due to Worsening of Schizophrenia, Dose Change, or Adverse Event at Month 12 in the ITT Population | Unscheduled visits due to worsening of schizophrenia, dose change or adverse event including the hospitalizations due to psychiatric disorders during the study (i.e. from Visit 1 to Termination date + 30 days) in inpatients units, in emergency wards and in day clinics. | Month 12 | 
| The Effect of Quetiapine XR Versus Risperidone Regarding Health Economics Outcomes by Evaluating the Time Between First Study Drug Intake and First Hospitalization for Patients With 1 Hospitalization in the ITT Population |  | 12 months | 
| Number of Participants Using Antidepressants at Month 12 in the ITT Population | The number of participants who were taking at least 1 antidepressant at Month 12. Antidepressants are all concomitant medications classified in the Anatomical Therapeutic Chemical(ATC)Subgroup N06-Antidepressants. | 12 months | 
| The Effect of Quetiapine XR Versus Risperidone Regarding Health Economics Outcomes by Evaluating the Number of Participants Using Other Psychotropic Medications at Month 12 in the ITT Population | Other psychotropic medications include antiepileptics, anti-parkinson drugs, antipsychotics, and antidepressants. | 12 months | 
| The Compliance of Patients Taking Quetiapine XR Versus Risperidone at Month 12 by Evaluating the Number of Participants Who Returned Study Drug at Month 12 in the ITT Population |  | 12 months | 
| The Safety and Tolerability of Quetiapine XR Versus Risperidone by Evaluating the Number of Participants With a Treatment-emergent Adverse Event (TEAEs) at Month 12 in the Safety Population | Treatment-emergent adverse events are defined as adverse events that occurred after the first intake of the study medication (or on the same day). | 12 months | 
| The Safety and Tolerability of Quetiapine XR Versus Risperidone by Evaluating the Number of Participants Who Discontinued the Study Because of an TEAE at Month 12 in the Safety Population | Treatment-emergent adverse events are defined as adverse events that occurred after the first intake of the study medication (or on the same day). | 12 months | 
| The Safety and Tolerability of Quetiapine XR Versus Risperidone by Evaluating the Number of Participants Who Had at Least 1 Extra-pyramidal TEAE at Month 12 in the Safety Population | Treatment-emergent adverse events are defined as adverse events that occurred after the first intake of the study medication (or on the same day). | 12 months | 
| The Safety and Tolerability of Quetiapine XR Versus Risperidone by Evaluating the Number of Extra-pyramidal Events at Month 12 in the Safety Population | Extra-pyramidal events include tremor, hypokinesia, muscle rigidity, hyperkinesia, and extrapyramidal disorder. | 12 months | 
| The Safety and Tolerability of Quetiapine XR Versus Risperidone by Evaluating the Number of Participants Who Had at Least 1 Cardiac TEAE at Month 12 in the Safety Population | Treatment-emergent adverse events are defined as adverse events that occurred after the first intake of the study medication (or on the same day). | 12 months | 
| The Safety and Tolerability of Quetiapine XR Versus Risperidone by Evaluating the Mean Change From Baseline to Month 12 in Prolactin Levels in the Safety Population | The normal range for men is 0 to 14, and for women is 0 to 24. | 12 months | 
| The Safety and Tolerability of Quetiapine XR vs Risperidone by Evaluating the Number of Participants at Month 12 in Safety Population With Individual Symptoms Assessed by the Modified Udvalg for Kliniske Undersogelser, Side Effect Rating Scale: Neurologic | Symptoms are graded according to degree (not present to severe) and causal relationship (improbable, possible, probable). An individual AE is defined as an AE with a worse degree compared with Baseline and with a possible or probable relationship to study drug. | 12 months | 
| The Safety and Tolerability of Quetiapine XR Versus Risperidone by Evaluating the Number of Participants at Month 12 in the Safety Population With Individual Symptoms Assessed by the Modified UKU: Hyperprolactinaemia in Women | Symptoms are graded according to degree (not present to severe) and causal relationship (improbable, possible, probable). Hyperprolactinaemia in women is defined as number of women who show the individual adverse event (AE) hyperprolactinaemia. An individual AE Hyperprolactinaemia is defined as an AE with a worse degree of hyperprolactinaemia compared with baseline and with a possible or probable relationship to study drug. | Month 12 | 
| The Safety and Tolerability of Quetiapine XR Versus Risperidone by Evaluating the Number of Participants at Month 12 in the Safety Population With Individual Symptoms Assessed by the Modified UKU: Sexual Dysfunction in Men | Symptoms are graded according to degree (not present to severe) and causal relationship (improbable, possible, probable). Sexual dysfunction in men is defined as number of men who show the individual adverse event (AE) sexual dysfunction. An individual AE sexual dysfunction is defined as an AE with a worse degree of sexual dysfunction compared with baseline and with a possible or probable relationship to study drug. | Month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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schizophrenia, SWNK