Safety and Efficacy of Zicronapine in Patients With Schizophrenia

Study Overview
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Brief Summary
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To assess the effect of zicronapine versus risperidone on metabolic parameters comprising body weight, body mass index (BMI), waist circumference, levels of fasting blood lipids and glucose during 6 months of treatment.

Detailed Description
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Schizophrenia is a serious and disabling mental disorder that affects approximately 1% of the world's population. Antipsychotic drugs remain the cornerstone in the pharmacotherapy of schizophrenia. There are a number of antipsychotic drugs in use but none is ideal, in particular because their safety profile is complex and their effectiveness is limited. Thus, present treatment options leave room for improvement and call for new, more effective pharmacotherapies for the treatment of schizophrenia. In the current study, non-acute patients with schizophrenia will be randomised to blinded treatment with either zicronapine or a standard antipsychotic treatment for 24 weeks. The safety (with focus on metabolic parameters) and efficacy of zicronapine will be evaluated in comparison to risperidone.

Official Title
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A 6-month, Randomised, Double-blind, Parallel-group, Risperidone-controlled, Fixed-dose Study Evaluating the Safety and Efficacy of Zicronapine in Patients With Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: Zicronapine
* Drug: Risperidone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient meets the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision (DSM-IV-TR) criteria for schizophrenia The patient is a man or woman, ≥18 and ≤65 years old The patient has a PANSS total score ≥60 and ≤100 (extremes included) at screening and baseline Exclusion Criteria: The patient has a current, predominant Axis I psychiatric disorder other than schizophrenia as defined in the DSM-IV-TR The patient has a current diagnosis or a history of substance dependence (except nicotine) or substance abuse (except cannabis) according to the DSM-IV-TR criteria ≤6 months prior to screening The patient is at significant risk of harming him/herself or others according to the investigator's judgement (assisted by the assessment of suicidal ideation and behaviour using the C-SSRS) The patient is resistant to antipsychotic treatment according to the investigator's judgement or has been treated with clozapine ≤3 months prior to screening The patient has experienced an acute exacerbation requiring hospitalisation ≤3 months prior to screening or between screening and baseline The patient has been treated with risperidone or paliperidone ≤6 months prior to screening Other inclusion and exclusion criteria may apply.

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zicronapine<br> | Drug: Zicronapine<br>* 7.5 mg/day; orally<br>* Other names: Past name: Lu 31-130;|
| Active Comparator: Risperidone<br> | Drug: Risperidone<br>* 5 mg/day; orally<br>* Other names: Risperdal®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the effect of zicronapine versus risperidone on body weight (and BMI) |  | 6 months | 
| To assess the effect of zicronapine versus risperidone on waist circumference |  | 6 months | 
| To assess the effect of zicronapine versus risperidone on levels of fasting blood lipids |  | 6 months | 
| To assess the effect of zicronapine versus risperidone on levels of fasting blood glucose |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the overall safety and tolerability of zicronapine versus risperidone during 6 months of treatment by comparing the frequencies of adverse events sorted by system organ class and preferred term. |  | 6 months | 
| To assess the potential of zicronapine versus risperidone to induce extrapyramidal symptoms using change from baseline to each assessment in the AIMS, BARS, and SAS total scores | Abnormal Involuntary Movement Scale (AIMS), Barnes Akathisia Scale (BARS), and Simpson Angus Scale (SAS) total scores | 6 months | 
| To assess the effect of zicronapine versus risperidone on serum prolactin levels |  | 6 months | 
| To assess the effect of zicronapine on suicidal ideation and behaviour using the Columbia Suicide-Severity Rating Scale (C-SSRS) |  | 6 months | 
| To assess the effect of zicronapine versus risperidone on electrocardiogram (ECG) parameters |  | 6 months | 
| To assess the efficacy of zicronapine versus risperidone following 6 months of treatment using change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score |  | 6 months | 
| To assess the efficacy of zicronapine versus risperidone using change from baseline to each assessment in the PANSS total score and PANSS subscale scores (Positive Symptoms, Negative Symptoms, and General Psychopathology) |  | 6 months | 
| To assess the efficacy of zicronapine versus risperidone by comparing the proportions of responders (using two definitions of response: ≥20% and ≥50% decrease from baseline in PANSS total score) |  | 6 months | 
| To assess the efficacy of zicronapine versus risperidone on global improvement using change from baseline to each assessment in the Clinical Global Impression - Severity of Illness (CGI-S) score |  | 6 months | 
| To assess the effect of zicronapine versus risperidone on personal and social functioning using the Personal and Social Performance Scale (PSP) |  | 6 months | 
| To assess the effect of zicronapine versus risperidone on functioning using the Global Assessment of Functioning scale (GAF) |  | 6 months | 
| To assess the effect of zicronapine versus risperidone on quality of life using the disease-specific Schizophrenia Quality of Life scale (S-QoL) |  | 6 months | 
| To assess the effect of zicronapine versus risperidone on the patient's satisfaction with treatment using the Medication Satisfaction Questionnaire (MSQ) |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia, Antipsychotic, Risperidone, Lu 31-130