Comparison of Antipsychotic Combination Treatment of Olanzapine and Amisulpride to Monotherapy

Study Overview
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Brief Summary
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A study to examine whether an antipsychotic combination treatment of olanzapine and amisulpride is more effective than olanzapine and amisulpride alone.

Detailed Description
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Polypharmacy in antipsychotic therapy is an important issue when treating patients with schizophrenia. It is not well confirmed that a combination of two antipsychotic drugs lead to therapeutic benefit in contrast to monotherapy. However there is a highly frequent practice of combining atypical non-clozapine treatment that could be due to potential benefits when seeking alternatives to a high rate of non-response in acute phase. Therefore there is a need for further trials of sufficient power to address efficacy and safety issues of this regimen. Combining two selected atypical drugs in a complementary way may minimize side-effects and enhance efficacy. In order to specify these advantages it is intend to examine approaches to combination treatment: Amisulpride and olanzapine show complementing receptor binding profiles and have shown to have efficacy and good tolerability when administered in combination in retrospective studies. The object of this trial is to study whether acutely ill patients with combination of amisulpride and olanzapine are more frequently in symptomatic remission after 8 weeks than those with olanzapine or amisulpride monotherapy.

Official Title
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A Randomized Double-blind Controlled Trial to Assess the Benefits of Olanzapine and Amisulpride Combination Treatment in Acutely Ill Schizophrenia Patients. - COMBINE

Conditions
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Schizophrenia, Schizoaffective Disorder

Intervention / Treatment
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* Drug: Olanzapine
* Drug: Amisulpride
* Drug: Olanzapine and Amisulpride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with schizophrenia and schizoaffective disorder according to International Classification of Diseases (ICD-10); age 18-65; Positive and Negative Symptom Scale Total-Score ≥ 70 and two items of the positive symptom subscale ≥4. voluntary treatment after written informed consent legal capacity exclusion of pregnancy by laboratory test (Beta HCG) Exclusion Criteria: participation in other interventional studies with drugs or medical devices first episode patients physical disease that might have effects on the conduct or evaluation of the trial contraindications to medication according to experts information oversensitivity to active substance or other component of the drugs used known clozapine resistance suicidal ideation pregnancy or lactation which of pregnancy or absence save contraception dependency to sponsor or investigator institutionalization through judicial or regulatory order oversensitivity to placebo (mannite/aerosil)

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Olanzapine or Placebo<br> | Drug: Amisulpride<br>* 200-800 mg milligram(s)per day for 16 weeks<br>* Other names: Amisulprid Hexal;Drug: Olanzapine and Amisulpride<br>* Zyprexa: Coated tablet 5-20 mg milligram(s) per day for 16 weeks Amisulpride: Coated tablet 200-800 mg milligram(s)per day for 16 weeks<br>* Other names: Zyprexa, Amisuprid Hexal;|
| Active Comparator: Amisulpride or Placebo<br> | Drug: Olanzapine<br>* Coated tablet 5-20 mg milligram(s) per day for 16 weeks<br>* Other names: Zyprexa;Drug: Olanzapine and Amisulpride<br>* Zyprexa: Coated tablet 5-20 mg milligram(s) per day for 16 weeks Amisulpride: Coated tablet 200-800 mg milligram(s)per day for 16 weeks<br>* Other names: Zyprexa, Amisuprid Hexal;|
| Active Comparator: Olanzapine and Amisulpride<br> | Drug: Olanzapine<br>* Coated tablet 5-20 mg milligram(s) per day for 16 weeks<br>* Other names: Zyprexa;Drug: Amisulpride<br>* 200-800 mg milligram(s)per day for 16 weeks<br>* Other names: Amisulprid Hexal;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptomatic improvement of schizophrenia after 8 weeks of treatment in comparison to time of inclusion of patient measured py Positive and Negative Symptom Scale (PANSS) | Whether there is a symptomatic improvement of schizophrenia after 8 weeks of treatment in comparison to time of inclusion of patient measured py Positive and Negative Symptom Scale (PANSS) | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptomatic improvement of schizophrenia after 16 weeks of treatment in comparison to time of inclusion of patient measured py PANSS total score reduction | To study whether a combination treatment of olanzapine and amisulpride show a PANSS total score reduction from baseline to week 16. | 16 weeks. | 
| Symptomatic improvement of schizophrenia from baseline to week 2 up to week 16 measured by PANSS total score reduction. | Whether a combination treatment of olanzapine and amisulpride show a PANSS total score reduction from baseline to every 2 weeks up to week 16. | Every 2 weeks up to week 16. | 
| PANSS total score reduction from baseline to week 2 as a predictor of the change after 8 weeks | Whether a change of PANSS total score reduction from baseline to week 2 is a predictor of the change after 8 weeks | 8 weeks | 
| Serious adverse drug reactions | Frequency and severity of serious adverse drug reactions | 16 weeks | 
| Change of clinical condition measured by Clinical Global Impression Scale (CGI scale) | Whether there is a change of clinical condition measured by Clinical Global Impression Scale (CGI scale) | every 2 weeks from baseline up to week 16 | 
| Change of the subjective well-being measured by Subjective Wellbeing under Neuroleptics Scale (SWN-K) | Whether there is a change of the subjective well-being measured by Subjective Wellbeing under Neuroleptics Scale(SWN-K) | between week 0, 8, 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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schizophrenia, amisulpride, olanzapine, polypharmacy