Long-Term Efficacy and Safety of Asenapine Using Haloperidol as a Positive Control (41513)(COMPLETED)(P05785)

Study Overview
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Brief Summary
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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. The clinical development of asenapine, as described in the 2007 IDB appears to have antipsychotic activity with superior symptomatic control compared to placebo and an improved safety profile compared to currently available neuroleptics. Its fast dissolving formulation may further add to treatment compliance. While various titration schedules have been used in previous studies, dose increases at 5 mg BID (twice daily) up to 10 mg BID have been well tolerated. Therefore, further exploration in a larger group of subjects with acute exacerbation of schizophrenia using an asenapine flexible dosing design ( 5 or 10 mg BID) will mimic actual clinical practice in a long-term 52-week extension trial.

Official Title
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A Multicenter, Randomized, Double-Blind, Flexible-Dose, Long-Term Extension Trial of the Safety and Maintenance of Effect of Asenapine Using Haloperidol Positive Control in Subjects Who Complete Protocol 041023 [NCT00156104]

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: Haloperidol
* Drug: Asenapine
* Drug: Asenapine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Completed the short-term 041023 trial (NCT00156104) Continued to meet all demographic and procedural inclusion criteria of the short-term trial upon entry into this long-term extension trial Sign a written informed consent for the 041513 trial. Demonstrated an acceptable degree of compliance with trial medication in the short-term trials in the opinion of the investigator Exclusion Criteria: CGI-S (Clinical Global Impressions of Severity of Illness) score of greater than or equal to 6 (severely psychotic) Occurrence(s) of AEs (adverse events) or other clinically significant findings that would prohibit their continuation Met any of exclusion criteria regarding medical/psychiatric status listed in the 041023 short-term trial Met exclusion criteria for medication status in short-term trials except for antidepressants and mood stabilizers.

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 |
| --- | --- |
| Active Comparator: Haloperidol/Haloperidol<br>Haloperidol in original study (NCT00156104) and in current long-term extension. | Drug: Haloperidol<br>* 2-8 mg BID<br>|
| Experimental: Asenapine/Asenapine<br>Asenapine in original study and asenapine in current long-term extension. | Drug: Asenapine<br>* 5 or 10 mg BID<br>|
| Experimental: Placebo/Asenapine<br>Double-Blind subjects randomized to only placebo medication for 6 weeks in the short-term 041023 asenapine trial, were randomized (double-blind) into the long-term 041513 asenapine extension trial and received asenapine 5 mg BID for Week 1. After Week 1, subjects received asenapine (either 5 mg BID or 10 mg BID) for the remainder of the 52-week trial. | Drug: Asenapine<br>* 5 or 10 mg BID<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Loss of Effect Over Time | Loss of effect in subjects who had >=30% decrease from baseline in Positive and Negative Syndrome Scale (PANSS) score at the end of the original trial (NCT00156104) preceding the long-term extension. PANSS is a 30-item clinician-rated instrument for assessing symptoms of schizophrenia. Scores range from 30-210; higher scores indicate greater severity. Loss of effect = increase in total PANSS >=30% from start of current study; subjective worsening of schizophrenia/request for dose increase; Clinical Global Impressions of Severity of Illness score >=6; discontinuation for lack of efficacy. | Throughout the 52 weeks of the trial. | 
| Median Survival Time of Effect | Kaplan-Meier estimate of median time to loss of effect in subjects who had >=30% decrease from baseline in PANSS score at the end of the original trial (NCT00156104) preceding the long-term extension. PANSS is a 30-item clinician-rated instrument for assessing symptoms of schizophrenia. Scores range from 30-210; higher scores indicate greater severity. Loss of effect = increase in total PANSS >=30% from start of current study; subjective worsening of schizophrenia/request for dose increase; Clinical Global Impressions of Severity of Illness score >=6; discontinuation for lack of efficacy. | 52 Weeks |