Efficacy and Safety of Asenapine With Placebo and Olanzapine (41022)(P05947)

Study Overview
=================
Brief Summary
-----------------
Schizophrenia is a brain disease. The primary features of schizophrenia are characterized by Positive symptoms (symptoms that should not be there, inability to think clearly, to distinguish reality from fantasy i.e., hearing voices) and Negative symptoms (a reduction or absence of normal behaviors or emotions, i.e., unable to manage emotions, make decisions and relate to others). Other symptoms include reduced ability to recall and learn new information, difficulty with problem solving, or maintaining productive employment. The symptoms of schizophrenia may be due to an imbalance in chemicals in the brain, primarily dopamine and serotonin, which enables brain cells to communicate with each other. Asenapine is an investigational drug that may help to correct the imbalance in dopamine and serotonin. This is a 6 week study to test the efficacy and safety of asenapine and a comparator agent (olanzapine) in the treatment of patients with schizophrenia. Patients that complete this trial will have the option of continuing in an additional one year extension trial.

Official Title
-----------------
A Multicenter, Randomized, Double-Blind, Flexible-Dose, 6-Week Trial of the Efficacy and Safety of Asenapine Compared With Placebo Using Olanzapine Positive Control in Subjects With an Acute Exacerbation of Schizophrenia

Conditions
-----------------
Schizophrenia

Intervention / Treatment
-----------------
* Drug: asenapine
* Drug: Placebo
* Drug: Olanzapine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Currently suffering from an acute exacerbation of schizophrenia. Exclusion Criteria: Have an uncontrolled, unstable medical condition. Have any other psychiatric disorder other than schizophrenia as a primary diagnosis.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>asenapine 5-10mg BID | Drug: asenapine<br>* Asenapine 5-10mgBID<br>|
| Placebo Comparator: 2<br>Placebo | Drug: Placebo<br>* Matched against asenapine and olanzapine<br>|
| Active Comparator: 3<br>olanzapine 10-20 mg QD | Drug: Olanzapine<br>* 10-20 mg QD<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in total Positive and Negative Syndrome Scale (PANSS) score at endpoint (6-week double-blind or last assessment after baseline) from baseline | A 30-item, clinician rated instrument for assessing the symptoms of schizophrenia. Ratings for each item could range from 1 (absent) to 7 (extreme). | Screen, baseline, days 4, 7, 14, 21, 28, 35, 42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in PANSS subscale and Marder factor score Clinical Global Impression-Severity of Illness (CGI-S) scores | This was not a prespecified key secondary outcome | Screen, baseline, Days 4,7,14,21,28,35,42 | 
| Clinical Global Impression Improvement (CGI-I) scores | This was not a prespecified key secondary outcome | Days 4,7,14,21,28,35,42 | 
| Neurocognition and cognitive functioning | This was not a prespecified key secondary outcome | Baseline , day 42 | 
| Anxiety | This was not a prespecified key secondary outcome | Baseline, day 42 | 
| Suicidal thinking | This was not a prespecified key secondary outcome | Baseline, day 42 | 
| Quality of life and patient functionality | This was not a prespecified key secondary outcome | Baseline, day 42 | 
| Readiness to discharge, at scheduled assessments and endpoint from baseline | This was not a prespecified key secondary outcome | Baseline up to day 14 | 
| Extrapyramidal symptoms | This was not a prespecified key secondary outcome | Baseline, Days 4,7,14,21,28,35,42 | 
| Laboratory parameters | This was not a prespecified key secondary outcome | Baseline, Days 14,,28,,42 | 
| Vital signs | This was not a prespecified key secondary outcome | Baseline, Days ,14,21,28,42 | 
| Weight | This was not a prespecified key secondary outcome | Baseline, Days 14,,28,,42 | 
| Electrocardiograms (ECGs) | This was not a prespecified key secondary outcome | Baseline, Days ,14, 28, 42 | 
| Adverse events (including serious adverse events) | This was not a prespecified key secondary outcome | Screen, baseline, Days 4,7,14,21,28,35,42 and recorded continuously for AEs up to 7 days after endpoint | 
| Serious adverse events (SAEs) up to 30 days after endpoint | This was not a prespecified key secondary outcome | Screen, baseline, Days 4,7,14,21,28,35,42 and recorded continuously for AEs up to 30 days after endpoint |