A Study to Evaluate the Effects of Once Daily Doses of AQW051 on Cognition, in Stable Schizophrenia Patients

Study Overview
=================
Brief Summary
-----------------
This is a study in chronic stable Schizophrenia with the purpose to answer the question of whether agonism of the nicotinic alpha7 receptor is capable of enhancing cognition in a well defined chronic stable patient population treated with antipsychotics as standard of care, and thus to support the future development of AQW051 for the treatment of cognitive impairment associated with Schizophrenia (CIAS).

Official Title
-----------------
A 12 Week, Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Effects of Once Daily Doses of AQW051 on Cognition, in Stable Schizophrenia Patients

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

Intervention / Treatment
-----------------
* Drug: AQW051
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of schizophrenia Symptomatically stable and currently treated with a stable regimen for at least 3 (three) months prior to dosing with one of the following second generation of antipsychotics: risperidone, paliperidone, quetiapine, ziprasidone, aripiprazole. Specific cognitive impairment Smokers and non-smokers Exclusion Criteria: Current treatment with an anticholinergic or other agent known to adversely interfere with the cholinergic system, and/ or treatment with cholinesterase inhibitor within the last three (3) months prior to dosing. Current treatment with conventional antipsychotics (e.g fluphenazine, haloperidol) or clozapine. History of neuroleptic malignant syndrome. Diagnosis of substance abuse (other than nicotine) within the last month and alcohol or substance dependence (other than nicotine) within the last 6 months. Score 4 or 5 on the Suicidal Ideation item or any yes on the Suicidal Behavior item of the CSSR-S that is related to suicidal behavior occurring during the last 2 years Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AQW051 10 mg/day<br>Two 5mg AQW051 capsules will be taken orally daily by patients from Day 1 until Day 84. | Drug: AQW051<br> <br> |
| Placebo Comparator: Placebo to AQW051<br>Matching placebo administered orally. | Drug: Placebo<br> <br> |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual learning and memory at 4 weeks | The primary objective is to evaluate the pro-cognitive effects of AQW051 in a chronic stable schizophrenic patient population at week 4 as measured by the absolute change from baseline in CPAL number of errors (CogState battery) at week 4. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect on cognitive function after 12 weeks of treatment - CogState test battery. | Change from baseline will be analyzed using a mixed model for repeated measures, including baseline value as covariate, time (timepoint), treatment as fixed effects and treatment*time interaction term and patient as random effect. Appropriate contrasts will be used to compare treatments at each timepoint. | Baseline, 12 weeks | 
| Effect on cognitive function after 12 weeks of treatment - MCCB | Change from baseline will be analyzed using a mixed model for repeated measures, including baseline value as covariate, time (timepoint), treatment as fixed effects and treatment*time interaction term and patient as random effect. Appropriate contrasts will be used to compare treatments at each timepoint. | Baseline, 12 weeks | 
| Number of patients with adverse events | Summarized statistics on adverse events will be reported under categories such as total adverse events, serious adverse events and death. | 12 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
schizophrenia, chronic stable schizophrenia, cognition, memory, visual learning, CogState