Pharmacodynamic/Pharmacokinetic Study of AQW051 in Schizophrenia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00825539
First received: January 19, 2009
Last updated: February 21, 2013
Last verified: February 2013
  Purpose

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 Intervention Phase
Schizophrenia
Drug: AQW051
Drug: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, 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.

Resource links provided by NLM:


Further study details as provided by Novartis:

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. [ Time Frame: 2 years (Part 1: 1 year) ] [ Designated as safety issue: Yes ]
  • Part 2: Assess safety and tolerability of multiple doses of AQW051 schizophrenia patients. [ Time Frame: Part 2: 8 months ] [ Designated as safety issue: Yes ]

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: Time Frame: 2 years (Part 1: 1 year; Part 2: 8 months) ] [ Designated as safety issue: No ]
  • Measure: To determine the relationship of exposure to brain activation after a single dose of AQW051 in people with schizophrenia. (Part 1) [ Time Frame: 2 years (Part 1: 1 year; Part 2: 8 months) ] [ Designated as safety issue: No ]
  • Measure: To determine the dose-exposure response relationship of multiple doses of AQW051 in people with schizophrenia. (Part 2) [ Time Frame: 2 years (Part 1: 1 year; Part 2: 8 months) ] [ Designated as safety issue: No ]
  • Measure: To explore effects of multiple doses of AQW051 on measures of cognition in people with schizophrenia. (Part 2) [ Time Frame: 2 years (Part 1: 1 year; Part 2: 8 months) ] [ Designated as safety issue: No ]

Enrollment: 68
Study Start Date: January 2009
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Drug: Placebo
Experimental: AQW051 Drug: AQW051
N/A

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Diagnosis of schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders IV (DSM IV/DSM IV TR)
  2. 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.
  3. 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
  4. 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
  5. Subjects must be symptomatically stable and not suffer from an acute exacerbation of their psychosis
  6. 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.

  7. 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.
  8. 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:

  1. Current treatment with conventional antipsychotics (e.g. fluphenazine, haloperidol) or clozapine
  2. Current treatment with an anticholinergic or other agent known to adversely interfere with the cholinergic system
  3. Subjects with a DSM-IV diagnosis of substance abuse (other than nicotine) within the last month.
  4. 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
  5. 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
  6. 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00825539

Locations
United States, California
West LA VA Healthcare Center (UCLA)
Los Angeles, California, United States, 90073
United States, Illinois
Department of Psychiatry & Behavioural Sciences, Feinberg School of Medicine (Northwestern University)
Chicago, Illinois, United States, 60611
United States, Maryland
Maryland Psychiatric Research Centre, Spring Grove Hospital Grounds
Baltimore, Maryland, United States, 21228
United States, Massachusetts
Massachusetts General Hospital (Freedom Trail Clinic)
Boston, Massachusetts, United States, 02115
United States, Missouri
Washington University
St Louis, Missouri, United States, 63110
United States, New York
Columbia University
New York, New York, United States, 10032
United States, North Carolina
JUH Clinical Research (Duke University),
Butner, North Carolina, United States, 27509
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00825539     History of Changes
Other Study ID Numbers: CAQW051A2202
Study First Received: January 19, 2009
Last Updated: February 21, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
Schizophrenia
Manic depression
anxiety

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders

ClinicalTrials.gov processed this record on August 19, 2014