Efficacy Study Exploring the Effects on Cognition of Sertindole Versus Comparator in Patients With Schizophrenia

Study Overview
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Brief Summary
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The objective of this study is to explore the neurocognitive efficacy of Sertindole versus comparator in patients with schizophrenia using the MCCB.

Detailed Description
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Sertindole is an atypical antipsychotic approved in the European Union (EU) for use in patients with schizophrenia who are intolerant to at least one other antipsychotic agent. During clinical development sertindole was found to be as effective in the treatment of schizophrenia as the first-generation antipsychotic haloperidol and as the second-generation antipsychotic risperidone. Sertindole is generally well tolerated and has a benign side-effect profile, including an absence of sedation, no effect on plasma prolactin levels, moderate weight gain, no anticholinergic-mediated cognitive impairment and a low rate of extrapyramidal symptoms (EPS). Sertindole has been shown to prolong the QT interval and is contraindicated in patients with prolonged QT interval and in patients receiving drugs known to significantly prolong the QT interval. The study is designed to provide data on the neurocognitive properties of sertindole versus quetiapine in patients with schizophrenia. Efficacy for cognitive impairment is assessed in patients who are in a stable phase of their illness, with a predefined maximum level of symptoms that will allow them to be included in the study. Prior antipsychotic medication will be withdrawn (down-tapered) and patients will be randomly assigned to one of the study drugs. Cognitive deficiencies are an important feature of schizophrenia and correlate strongly with functional impairment. Improving functional outcomes in schizophrenia has a high priority and has resulted in the initiation of a program called Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) leading to the development of a neuropsychological test battery, the MCCB which is used in this study.

Official Title
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A Randomised, Double-Blind, Parallel-Group, Flexible-Dose Study Exploring the Neurocognitive Effect of Sertindole Versus Comparator in Patients With Schizophrenia Using the MATRICS Consensus Cognitive Battery (MCCB)

Conditions
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Schizophrenia, Cognition

Intervention / Treatment
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* Drug: Sertindole
* Drug: Quetiapine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary diagnosis of schizophrenia Man or woman, aged between 18 and 55 years Exclusion Criteria: Current Axis I primary psychiatric diagnosis other than schizophrenia Not previously received antipsychotic drugs for schizophrenia Acute exacerbation requiring hospitalisation within the last 3 months Clinically significant extrapyramidal symptoms Clinically significant cardiovascular disease, congestive heart failure, cardiac hypertrophy, arrhythmia or bradycardia Congenital long QT syndrome or a family history of this disease, or known acquired QT interval prolongation Significant ECG abnormalities Hypokalaemia or hypomagnesaemia In concurrent treatment with drugs inhibiting the P450 enzymes system CYP3A

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sertindole<br> | Drug: Sertindole<br>* Once daily oral dose. Day 1-20: 4-16 mg/day (titration period). Day 21-84: 12, 16 or 20 mg/day (flexible treatment period).<br>|
| Active Comparator: Quetiapine<br> | Drug: Quetiapine<br>* Twice daily oral dose. Day 1-20: 50-500 mg/day (titration period). Day 21-84: 400, 500 or 600 mg/day (flexible treatment period).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurocognitive effect of treatment based on the overall composite score on the MCCB |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Domain specific scores on MCCB; PANSS total score, PANSS positive symptom subscale score, PANSS negative symptom subscale score, and PANSS general psychopathology subscale score; CGI-S, CDSS and GAF scores; QLS and UPSA total and subscale scores; ECGs |  | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia, Cognition, MATRICS Consensus Cognitive Battery