Effect of AQW051 on Cognitive Function in Patients With Chronic Stable Schizophrenia

Study Overview
=================
Brief Summary
-----------------
This PoC study is designed to assess the cognitive effects of doses of AQW051 in patients with chronic stable schizophrenia.

Official Title
-----------------
A Randomized, Double-blind, Placebo-controlled, Cross-over, Single-dose Study to Evaluate the Effects of AQW051 on Cognitive Function in Patients With Chronic Stable Schizophrenia Including a One Week Multiple-dose Extension to Assess the Persistence of Observed Effects and a Multiple-dose Cross Over Study in Non Smokers Only.

Conditions
-----------------
Schizophrenia Disorders

Intervention / Treatment
-----------------
* Drug: Placebo (single and multiple doses)
* Drug: AQW051 2 mg (single and multiple doses)
* Drug: AQW051 15mg (single and multiple doses)
* Drug: AQW051 100mg (single dose), and 50mg (multiple doses)


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. Any clinically significant suicidal ideation (Type 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) in the last month) or previous history of suicide behavior 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: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo (single and multiple doses)<br> <br> |
| Experimental: AQW051 Dose 1<br> | Drug: AQW051 2 mg (single and multiple doses)<br> <br> |
| Experimental: AQW051 Dose 2<br> | Drug: AQW051 15mg (single and multiple doses)<br> <br> |
| Experimental: AQW051 Dose 3<br> | Drug: AQW051 100mg (single dose), and 50mg (multiple doses)<br> <br> |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of single oral doses of AQW051 versus placebo on cognitive function as measured by selected CogState tests |  | 132 days Part A, 121 days Part B (screening to study completion) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of single oral doses of AQW051 versus placebo on cognitive function as measured by selected MATRICS Consensus Cognitive Battery (MCCB) tests |  | 132 days Part A, 121 days Part B (screening to study completion) | 
| Effects of multiple oral doses of AQW051 versus placebo on cognitive function as measured by selected CogState tests and selected MCCB tests |  | 132 days Part A, 121 days Part B (screening to study completion) | 
| Correlation of the cognitive domains measured by MCCB versus CogState |  | 132 days Part A, 121 days Part B (screening to study completion) | 
| Pharmacokinetics, safety and tolerability of single and multiple doses of AQW051 as compared to placebo |  | 132 days Part A, 121 days Part B (screening to study completion) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hallucinations,, psychotic,, delusions,, cognitive deficits