Efficacy and Safety of Asenapine Using an Active Control in Subjects With Schizophrenia or Schizoaffective Disorder (25517)(P05935)

Study Overview
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Brief Summary
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The primary features of schizophrenia and schizoaffective disorder are characterized by positive (inability to think clearly and distinguish reality from fantasy) and negative symptoms (reduction or absence of normal behavior or emotions). Other symptoms include reduced ability to recall and learn information, difficulty in problem solving or maintaining productive employment. Asenapine is an investigational drug that may help to correct the above characteristics of schizophrenia by altering the inbalance of brain hormones such as dopamine and serotonin. This is a 12-month trial that will test the efficacy and safety of asenapine using an active comparator (olanzapine) in the treatment of patients with schizophrenia. Patients who complete the 12-month trial will have the option of continuing on drug until the treatment code for the 12-month trial is unblinded.

Official Title
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A Phase III, Double-Blind, Randomized, Active-Controlled, Two-Armed, Multicenter, Efficacy and Safety Assessment (ACTAMESA) of Org 5222 and Olanzapine in the Treatment of Patients With Schizophrenia or Schizoaffective Disorder

Conditions
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Schizophrenia, Schizoaffective Disorder

Intervention / Treatment
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* Drug: asenapine
* Drug: olanzapine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject with schizophrenia or schizoaffective disorder. Subject must sign a written informed consent. Exclusion Criteria: Have an uncontrolled, unstable, clinically significant medical condition. Have any other psychiatric disorder other than schizophrenia as a primary diagnosis including depression.

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Experimental: Arm 1<br> | Drug: asenapine<br>* Flexible dose, 1-2 tablets sublingual two times per day (1 or 2 tablets in the morning and 1 or 2 tablets in the evening). Each tablet contains either 5 mg asenapine or matching placebo.<br>* Other names: SCH 900274;|
| Active Comparator: Arm 2<br> | Drug: olanzapine<br>* Oral capsules (5 mg or placebo); 1 to 2 tablets twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in total PANSS score at endpoint (52-week double-blind or last assessment after baseline) from baseline |  | Screening, Baseline, Week 2, 4, 6, 8, 12, 20, 28, 36, 44, 52 (endpoint) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in PANSS subscale scores and Marder factor scores |  | At weeks 2, 4, 6, 8, 12, 20, 28, 36, 44 and endpoint | 
| Changes in CGI-S |  | At each assessment time point from baseline | 
| Patient functionality and subjective well-being (as measured by LOF, SF-12 and SWN) |  | At weeks 8, 20, 28, 36, 44 and endpoint | 
| Severity of depressed mood (as measured by the Calgary Depression Scale for Schizophrenia) |  | At weeks 6, 28 and endpoint | 
| Resource utilization (as measured by frequency and length of hospital stay) |  | During the study period | 
| Satisfaction with treatment in comparison with previous treatment as assessed by the investigator and patient) |  | At endpoint | 
| Population kinetics |  | Plasma samples at weeks 2 and 6 in comparison with baseline | 
| Pharmacogenetics (as part of a global effort to investigate possible associations between genetic polymorphisms in relation to response to asenapine and related drugs and in relation to characteristics of schizophrenia and related conditions) |  | During the study period | 
| Safety and tolerability: EPS (AIMS, BARS, SARS) |  | At weeks 1, 3, 6, 16, 24, 32, 40 and endpoint | 
| Adverse Events |  | continuously and up to 7 days after endpoint | 
| Pregnancy Test |  | At endpoint | 
| Blood Test |  | At weeks 1, 3, 6, 16, 24, 32, 40 and endpoint | 
| Weight and vital signs |  | at all assessment time points from baseline | 
| ECGs |  | Weeks 3, 6, 24, and endpoint |