A Study of the Cataractogenic Potential of Seroquel and Risperdal in the Treatment of Participants With Schizophrenia or Schizoaffective Disorder

Study Overview
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Brief Summary
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This Phase IV, randomized, parallel-group study is designed to evaluate the cataractogenic potential of quetiapine fumarate (SEROQUEL) compared with that of a putative non-cataractogenic antipsychotic medication risperidone (RISPERDAL). This study is being conducted to fulfill the SEROQUEL Phase IV commitment regarding evaluation of cataractogenic potential.

Official Title
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A Multicenter, Open Label, Flexible-dose, Parallel-group Evaluation of the Cataractogenic Potential of Quetiapine Fumarate (Seroquel) and Risperidone (Risperdal) in the Long Term Treatment of Participants With Schizophrenia or Schizoaffective Disorder

Conditions
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Schizophrenia, Schizoaffective Disorder

Intervention / Treatment
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* Drug: quetiapine fumarate
* Drug: risperidone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women age 18 to 65 Both Eyes present with lenses intact (no previous cataract extractions) Stable place of residency Exclusion Criteria: History of corneal surgery Legal blindness (defined as best corrected visual acuity of 20/200 or worse in one or both eyes Previous participation in this study

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: 1<br>Quetiapine fumarate | Drug: quetiapine fumarate<br>* flexible dose oral<br>* Other names: ICI 204,636;|
| Active Comparator: 2<br>Risperidone | Drug: risperidone<br>* flexible dose oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence of a Cortical (C) Type of Cataractogenic Potential Events in Participants as Assessed and Agreed by 2 Independent, Treatment-masked Ophthalmologists Using the Lens Opacities Classification System II (LOCS II ) Grading Scale | Presence of C type of cataractogenic potential event in participant was defined if any LOCS II grades of 2, 3, 4, 5 (with any grade of 0, trace,1 at randomization) assessed and agreed by 2 independent, treatment-masked ophthalmologists at any post-randomization assessment in one or both eyes. 0= no cataract; 5 is worst. There are no subscales. 0 is the best, 5 is the worst. | Randomization to Month 24 | 
| Presence of a Nuclear Opalescence (N) Type of Cataractogenic Potential Events in Participants as Assessed and Agreed by 2 Independent, Treatment-masked Ophthalmologists Using the LOCS II Grading Scale | Presence of N type of cataractogenic potential event in Participants was defined if any LOCS II grades of 2, 3, 4 (with grade at rand equals 0,1), or if the LOCS II grades of 3,or 4 (with grade at randomization=2) assessed and agreed by 2 independent, treatment-masked ophthalmologists at any post-randomization assessment in one or both eyes. 0 is the best, 4 is the worst. | Randomization to Month 24 | 
| Presence of a Posterior Subcapsular (P) Type Cataractogenic Potential Events in Participants as Assessed and Agreed by 2 Independent, Treatment-masked Ophthalmologists Using the LOCS II Grading Scale | Presence of P type of cataractogenic potential event in participant was defined if any LOCS II grades of 1, 2, 3 , 4 (with grade=0 at randomization) assessed and agreed by 2 independent, treatment-masked ophthalmologists at any post-randomization assessment in one or both eyes. 0 is the best, 4 is the worst. | Randomization to Month 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Positive and Negative Syndrome Scale (PANSS) Total Score | PANSS total score equals sum of the 30-items scores (range: 30-210). Each item has ( 1-7 units), 1 indicates absent psychosis symptom, and 7 - extreme symptom degree. Change in PANSS total score : total score at month 24 minus total score at randomization.Alleviation of psychotic symptoms are indicated by a negative change in PANSS total score. | Randomization to Month 24 | 
| Change in the PANSS Positive Subscale Score | PANSS Positive subscale score equals sum of the 7-items scores(range:7-49). Each item has ( 1-7 units), 1 indicates absent psychosis symptom, and 7 - extreme symptom degree. | Randomization to Month 24 | 
| Change in the PANSS Negative Subscale Score | PANSS Negative subscale score equals sum of the 7-items scores(range:7-49). Each item has ( 1-7 units), 1 indicates absent psychosis symptom, and 7 - extreme symptom degree. Change in PANSS Negative subscale score:score at month 24 minus score at randomization. Alleviation of negative psychotic symptoms are indicated by a negative change score. | Randomization to Month 24 | 
| Change in the PANSS Psychopathology Subscale Score | PANSS psychopathology subscale score equals sum of the 16-items scores(range:16-112). Each item has ( 1-7 units),1= absent psychosis symptom, 7= extreme symptom degree.Change in PANSS psychopathology subscale:score at month 24 minus score at randomization. Alleviation of general psychopathology symptoms are indicated by a negative change score. | Randomization to Month 24 | 
| Change in the Clinical Global Impression - Severity of Illness (CGI-S) Score | CGI-S score is accessed on a seven-graded scale ranging from most extremely ill/ very much worse (7) to normal/very much improved (1) , 1 is best. Change : score at month 24 minus score at randomization. | Randomization to Month 24 | 
| Change in Health-related Quality of Life as Measured by Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q SF) Total Score | Q-LES-Q total score is the sum of the 16 times of Q-LES-Q SF(range:16-80).Each item has a 5 point satisfaction level scale:from 1=very poor(worst value) to 5=very good(best).Larger values indicate a higher perceived quality of life enjoyment and satisfaction.Change in Q-LES-Q total score:total score at month 24 minus total score at randomization | Randomization to Month 24 | 
| Change in Personal Evaluation of Transitions in Treatment (PETiT) Total Score | PETiT total score is the sum of the 30 items of PETiT questionnaire(range:0-60) on subjects perceived well-being, adherence, tolerability, satisfaction with treatment. Each item is rated by participant with a 3 point frequency scale:2=often, 1=sometimes, 0=never.Change in PETiT total score: total score at month 24 minus total score at randomization | Randomization to Month 24 | 
| Number of Relapses of Schizophrenia or Schizoaffective Disorder | Relapse is defined as a hospital stay for psychiatric symptoms or a 2-point increase from baseline in the CGI severity score. CGI-S score ranges from 0-7 with 0 = Not Assessed, 1 = Normal, not at all and 7 = Among the most extremely ill subjects. | At Month 24 | 
| Change in Simpson-Angus Scale (SAS) Total Score | SAS total score is the sum of the 10 individual-item scores (range:0-40), with the score for each item ranging from 0 to 4, higher scores indicate greater severity of Parkinsonian symptoms. Change : total score at month 24 minus total score at randomization. Increase in Change of total score indicates an increase in extrapyramidal motor symptoms. | Randomization to Month 24 | 
| Change in Barnes Akathisia Rating Scale (BARS) Global Score | BARS global score is the 4th individual-item score on the BARS scale, the Global Assessment of Akathisia, with the score ranging from 0 (no evidence of akathisia) to 5 (severe akathisia). Change : score at month 24 minus score at randomization. Increase in Change of BARS global score indicates an increase in akathisia. | Randomization to Month 24 | 
| Change in Abnormal Involuntary Movement Scale (AIMS) Total Score | AIMS total score is the sum of the 10 individual-item scores(range:0-40), with the score for each item ranging from 0 to 4. Change : total score at month 24 minus total score at randomization. Increase in Change of total score indicates an increase in abnormal voluntary movements. The lower score means lower intensity of abnormal voluntary Movements. 0 is best, 4 is worst. Increase in Change of total score indicates an increase in abnormal voluntary Movements. | Randomization to Month 24 | 
| Number of Participants With Potential Extrapyramidal Symptoms (EPS) | Number of participants with adverse events potentially associated with EPS collected by MedDRA Preferred Terms as akathisia, bradykinesia, drooling, dyskinesia, dystonia, extrapyramidal disorder, grimacing, muscle rigidity, parkinsonism, restlessness, tardive dyskinesia, tremor | From start of the study treatment to last dose plus 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia, Schizoaffective Disorder