A Trial Comparing Risperidone Long-Acting Injection With Oral Antipsychotic in the Treatment of Early Psychosis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effectiveness, safety and tolerability of risperidone long-acting injection (LAI) versus oral antipsychotics in participants with recent onset psychosis (abnormal thinking and/or hallucinations).

Detailed Description
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This is an open-label (all people know identity of intervention), randomized (the study drug is assigned by chance), multicenter (conducted in more than 1 center), and exploratory study in participants with schizophrenia (psychiatric disorder with symptoms of emotional instability, detachment from reality) or schizoaffective disorder (mixed psychiatric disorder relating to complex psychotic state that has features of both schizophrenia and mood disorder). Duration of this study will be 24 months. Study assessment visits will be conducted at Screening, Baseline, Week 2, every 4 weeks till Week 22, at Week 28, every 12 weeks till Week 88 and at Week 104. All eligible participants will receive either risperidone long acting injection 25 milligram (mg) intramuscularly (into the muscle) along with their current oral medication (atypical antipsychotic - risperidone, quetiapine, olanzapine) or only their current oral medication. Efficacy will be evaluated primarily by Positive and Negative Syndromes Scale (PANSS), time to relapse and Social and Occupational Functioning Assessment Scale (SOFAS). Participants's safety will be evaluated throughout the study mainly by Abnormal Involuntary Movement Scale (AIMS), Barnes Akathisia Rating Scale (BARS), and Simpson Angus Scale (SAS).

Official Title
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An Open-Label Randomized Trial Comparing Risperdal Consta With Oral Antipsychotic Care in the Treatment of Early Psychosis

Conditions
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Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder, Psychotic Disorders

Intervention / Treatment
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* Drug: Risperidone long-acting injection (LAI)
* Drug: Oral Antipsychotic


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: In-patients or out-patients Primary Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) diagnosis of schizophrenia, schizophreniform disorder or schizoaffective disorder for no longer than 3 years after diagnosis and treatment of a psychotic illness Positive and Negative Syndrome Scale (PANSS) score of 60-120 at Visit 1 and 2 Currently on monotherapy atypical antipsychotic treatment below local label guidelines or treatment naive Able to complete self-assessments in either English or French Exclusion Criteria: Current primary Axis-1 diagnosis other than schizophrenia, schizophreniform disorder or schizoaffective disorder, according to DSM-IV Current drug or alcohol dependence Treatment with a depot antipsychotic within 3 months of study start Confirmed or suspected history of lack of tolerability, hypersensitivity or allergy to risperidone Risperidone non-responders (based on evidence of adequate trial of treatment)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 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: Risperidone long-acting injection (LAI)<br>Risperidone LAI 25 mg, 37.5 mg or 50 mg intramuscular injection will be administered every 2 weeks as per Investigator's discretion. An oral atypical antipsychotic will also be administered in the first 3 weeks following initiation of Risperidone LAI, and for a maximum of 3 weeks following a dose increase. | Drug: Risperidone long-acting injection (LAI)<br>* Risperidone LAI 25 mg, 37.5 mg or 50 mg intramuscular injection will be administered every 2 weeks as per Investigator's discretion.<br>|
| Active Comparator: Oral Antipsychotic<br>Oral antipsychotic (new or current treatment) will be administered in which daily dose range permitted will be risperidone 6 mg; olanzapine 20 mg; quetiapine 800 mg. Participants will be switched to another oral therapy as per Investigator's discretion. | Drug: Oral Antipsychotic<br>* Oral antipsychotic (new or current treatment) will be administered in which daily dose range permitted will be risperidone 6 mg; olanzapine 20 mg; quetiapine 800 mg.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 104 or Last Reported Visit (LRV) | The PANSS provides a total score (sum of the scores of all 30 items) and scores for 3 subscales, the positive subscale (7 items), the negative subscale (7 items), and the general psychopathology subscale (16 items), each rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme). The PANSS total score consists of the sum of all 30 PANSS items and ranges from 30 to 210. Higher scores indicate worsening. | Baseline, Week 104 or LRV | 
| Time to Relapse | Time to relapse was calculated from the start of the maintenance phase to date of relapse according to Csernansky: Psychiatric hospitalization; increased level of psychiatric care from start of maintenance period and 25 percent increase in total PANSS score from first maintenance visit, or 10 points increase where PANSS at start of maintenance period was 40 or less; deliberate self-injury, suicidal or homicidal ideation; violent to others; property damage; or substantial clinical deterioration, defined as Clinical Global Impression of Change (CGI-C) score of 6 (much worse). | Week 10 (post-stability) up to Week 104 or LRV | 
| Change From Baseline in Social and Occupational Functioning Assessment Scale (SOFAS) at Week 104 or LRV | The SOFAS focused exclusively on participants' level of social and occupational functioning. The SOFAS is a 100 point single item scale that rates functioning of a participant. The scale values range from 1=most impaired to 100=healthiest individual. The scale also includes a rating point of 0=missing information. | Baseline, Week 104 or LRV | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Calgary Depression Symptom Scale (CDSS) Score at Week 104 or LRV | Co-morbid depressive symptoms are evaluated by change in CDSS Score which was developed to assess symptoms of depression in participants with schizophrenia (psychiatric disorder with symptoms of emotional instability, detachment from reality, often with delusions and hallucinations, and withdrawal into the self). It consists of 9 items, each scored from 0 (absent) to 3 (severe). The total score is a sum of the scores of each item and may range from 0 to 27. Higher score more severe pathology. Data presented here represents the change from baseline to endpoint. | Baseline, Week 104 or LRV | 
| Change From Baseline in Young Mania Rating Scale (YMRS) at Week 104 or LRV | Co-morbid symptoms of mania are evaluated by change in YMRS Score which is an 11-item scale to assess symptoms of mania, Four items are rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe). The remaining items are rated on a scale from 0 (symptom not present) to 4 (symptom extremely severe). The YMRS total score ranges from 0 (the least) to 60 (the worst). | Baseline, Week 104 or LRV | 
| Change From Baseline Hamilton Anxiety Scale (HAM-A) Total Score at Week 104 or LRV | The HAM-A is a 14-item scale designed to measure anxiety in individuals. Each question reflects a symptom of anxiety and physical as well as mental symptoms are represented. The answers range from 0 which signifies a complete lack of that symptom to 4, which indicates a very severe show of anxiety with that symptom. Total score ranges from 0 to 56. Lower score indicates less affected. | Baseline, Week 104 or LRV | 
| Percentage of Participants With Relapse | Relapse was defined according to Csernansky: Psychiatric hospitalization; increased level of psychiatric care from start of maintenance period and 25 percent increase in total PANSS score from first maintenance visit, or 10 points increase where PANSS at start of maintenance period was 40 or less; deliberate self-injury, suicidal or homicidal ideation; violent to others; property damage; or substantial clinical deterioration, defined as CGI-C score of 6 (much worse). | Week 10 (post-stability) up to Week 104 or LRV | 
| Number of Participants With Cognitive Assessment Using Trail A | Cognitive assessments were done using Trail test A which measured variety of functions, including motor speed, visual scanning, attention and visual motor integration. Participants must connect numbered circles in a variety of orders. | Week -2, 104 or LRV | 
| Number of Participants With Cognitive Assessments Using Trail B | Cognitive assessments were done using Trail test B, which measured variety of functions, including motor speed, visual scanning, attention and visual motor integration. In Trail B, 2 sets of circles contain numbers and letters, and the participant must connect them in alternating order. Trail B is also a measure of executive functions as it requires planning and decision-making. | Week -2, 104 or LRV | 
| Total Words Score Over Time | Controlled Word Association Test (COWAT) was used to assess verbal fluency. Participants are given 3 different letters of the alphabet and asked to say as many words beginning with each letter within a controlled time. Participants are then asked to identify as many words as possible in 3 different categories (animals, fruits and vegetables) within a specified period of time. The total score is a sum of all three categories scores. The total score ranges from 0-90, the higher the score the higher the verbal fluency. | Baseline, Week 104 or LRV | 
| Change From Baseline in Drug Attitude Inventory (DAI-10) Score at Week 104 or LRV | The DAI, a 10-item scale to assess how the attitude of schizophrenia participants toward their medications may affect compliance. Respondents indicate 'true' or 'false' for each item. An overall calculated score ranged from -10 to 10, where a positive score indicated a positive subjective response (compliant), a negative score indicated non-compliance. Change: score at observation minus score at baseline. | Up to Week 104 or LRV | 
| Change From Baseline in Standardized Mental Component Scale Score in Short Form 36 (SF-36) at Week 104 or LRV | The SF-36 is a survey of participant health. It calculates two standardized scales: the standardized mental component scale and the standardized physical component scale. The standardized scales are calculated as weighted sums of the 8 scores, which are: vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health. Each item is scored on a 0-100 range; and standardized mental component scale score is calculated as weighted average of individual item scores on a 0-100 range, where 100 signify highest level of functioning. The change from baseline in mental component scale score was reported. | Up to Week 104 or LRV | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia, Schizoaffective disorder, Schizophreniform disorder, Risperidone, Risperdal Consta