Pharmacodynamic/Pharmacokinetic Study of AQW051 in Schizophrenia

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT00825539

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

9.7

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Part 1 of the study will assess the enhancement of task-related brain activation (BOLD response) in key brain areas in schizophrenia during the performance of working memory, episodic memory and visual activation tasks as measured by functional magnetic resonance imaging (fMRI) in people with schizophrenia. Part 2 of the study will assess the safety and tolerability of multiple doses of AQW051 in people with schizophrenia.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: AQW051 Drug: Placebo	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

68 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Single-dose, Placebo-controlled, Stratified, Randomized, Double-blind, Crossover to Study Pharmacodynamic Effects of AQW051 Followed by a 4-week Multiple-dose Safety and Tolerability in People With Chronic Stable Schizophrenia.

Study Start Date :

Jan 1, 2009

Actual Primary Completion Date :

Nov 1, 2011

Actual Study Completion Date :

Nov 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo	Drug: Placebo
Experimental: AQW051	Drug: AQW051

Arm

Intervention/Treatment

Placebo Comparator: Placebo

Drug: Placebo

Experimental: AQW051

Drug: AQW051

Outcome Measures

Primary Outcome Measures

Part 1: Assess BOLD response in key brain areas in schizophrenia patients during the performance of tasks as measured by (fMRI) in people with schizophrenia. [2 years (Part 1: 1 year)]
Part 2: Assess safety and tolerability of multiple doses of AQW051 schizophrenia patients. [Part 2: 8 months]

Secondary Outcome Measures

Measure: To assess the effects of a single dose of AQW051 on performance of working and episodic memory tasks in people with schizophrenia. (Part 1) [Time Frame: 2 years (Part 1: 1 year; Part 2: 8 months)]
Measure: To determine the relationship of exposure to brain activation after a single dose of AQW051 in people with schizophrenia. (Part 1) [2 years (Part 1: 1 year; Part 2: 8 months)]
Measure: To determine the dose-exposure response relationship of multiple doses of AQW051 in people with schizophrenia. (Part 2) [2 years (Part 1: 1 year; Part 2: 8 months)]
Measure: To explore effects of multiple doses of AQW051 on measures of cognition in people with schizophrenia. (Part 2) [2 years (Part 1: 1 year; Part 2: 8 months)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosis of schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders IV (DSM IV/DSM IV TR)
Subjects will be currently treated with the stable regimen of one or more of the following second generation antipsychotics: olanzapine, risperidone, paliperidone, quetiapine, ziprasidone, aripiprazole.
Subjects will meet the following symptom criteria:

Brief Psychiatric Rating Scale (BPRS) Hallucinatory Behavior or Unusual Thought Content item scores less than or equal to 5
BPRS Conceptual Disorganization item score less than or equal to 4
Simpson-Angus Scale (SAS) total score less than or equal to 6
Calgary Depression Scale (CDS) total score less than or equal to 10

Subjects will meet the following cognitive performance criteria:

Maximum performance level: Performance below 1.0 SD from perfect performance on the Hopkins Verbal Learning Test (HVLT) total (31 or less),
Minimum performance level: subject must be able to validly complete the fMRI cognitive paradigms
WTAR: 5th grade reading level assessment

Subjects must be symptomatically stable and not suffer from an acute exacerbation of their psychosis
Female subjects of childbearing potential must be using two acceptable methods of contraception, (e.g., intra-uterine device plus condom, spermicidal gel plus condom, diaphragm plus condom, etc.), from the time of screening and for the duration of the study, through study completion. Pregnancy tests are required of all female subjects regardless of reported sterilization.

When performed at screening and practice visit, the result of this test must be received before the subject may be dosed.

Male subjects must be using two acceptable methods of contraception, (e.g., spermicidal gel plus condom) for the entire duration of the studyuntil the Study Completion visit.
Subject must have sufficiently stable overall health, as determined by the Investigator. The regular intake of concomitant drugs will be allowed, if the patient is on stable treatment for at least 3 months prior to study enrollment and the concomitant drug does not belong to the list of medication that are not allowed according to Appendix 3. If the patient takes more than one concomitant medication, it is at the Investigator's discretion to decide about the patient's eligibility, depending on the nature of the concomitant medications and the patient's overall health.

Exclusion criteria:

Current treatment with conventional antipsychotics (e.g. fluphenazine, haloperidol) or clozapine
Current treatment with an anticholinergic or other agent known to adversely interfere with the cholinergic system
Subjects with a DSM-IV diagnosis of substance abuse (other than nicotine) within the last month.
Subjects with a history of significant head injury/trauma, as defined by:

Loss of consciousness (LOC) for more than 1 hour
Recurring seizures resulting from the head injury
Clear cognitive sequelae of the injury
Cognitive rehabilitation following the injury

Subjects with a medical or neurological disorder or treatment for such disorder that could interfere with the study medication of the assessment of the subject
Use of certain concomitant medication

No grapefruit or grapefruit juice is to be consumed for 14 days prior to dosing until 7 days following the last dose.

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	West LA VA Healthcare Center (UCLA)	Los Angeles	California	United States	90073
2	Department of Psychiatry & Behavioural Sciences, Feinberg School of Medicine (Northwestern University)	Chicago	Illinois	United States	60611
3	Maryland Psychiatric Research Centre, Spring Grove Hospital Grounds	Baltimore	Maryland	United States	21228
4	Massachusetts General Hospital (Freedom Trail Clinic)	Boston	Massachusetts	United States	02115
5	Washington University	Saint Louis	Missouri	United States	63110
6	Columbia University	New York	New York	United States	10032
7	JUH Clinical Research (Duke University),	Butner	North Carolina	United States	27509