Pharmacodynamic/Pharmacokinetic Study of AQW051 in Schizophrenia

NCT00825539 | Completed Phase 1

• 1 other identifier: CAQW051A2202
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 7

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.

Conditions

Schizophrenia

Keywords

Schizophrenia; Manic depression; anxiety

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• 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)

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Drug: Placebo

AQW051

EXPERIMENTAL

Drug: AQW051

Interventions

AQW051 DRUG

AQW051

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (7)

West LA VA Healthcare Center (UCLA)

Los Angeles, California, 90073, United States

Location

Department of Psychiatry & Behavioural Sciences, Feinberg School of Medicine (Northwestern University)

Chicago, Illinois, 60611, United States

Location

Maryland Psychiatric Research Centre, Spring Grove Hospital Grounds

Baltimore, Maryland, 21228, United States

Location

Massachusetts General Hospital (Freedom Trail Clinic)

Boston, Massachusetts, 02115, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Columbia University

New York, New York, 10032, United States

Location

JUH Clinical Research (Duke University),

Butner, North Carolina, 27509, United States

Location

Related Publications (1)

• Barch DM, Marder SR, Harms MP, Jarskog LF, Buchanan RW, Cronenwett W, Chen LS, Weiss M, Maguire RP, Pezous N, Feuerbach D, Lopez-Lopez C, Johns DR, Behrje RB, Gomez-Mancilla B. Task-related fMRI responses to a nicotinic acetylcholine receptor partial agonist in schizophrenia: A randomized trial. Prog Neuropsychopharmacol Biol Psychiatry. 2016 Nov 3;71:66-75. doi: 10.1016/j.pnpbp.2016.06.013. Epub 2016 Jun 28.

  PMID: 27371157 DERIVED

Related Links

• Results for CAQW051A2202 from the Novartis Clinical Trials website

MeSH Terms

Conditions

Schizophrenia; Bipolar Disorder; Anxiety Disorders

Interventions

3-(6-p-tolylpyridin-3-yloxy)-1-azabicyclo(2.2.2)octane

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Bipolar and Related Disorders; Mood Disorders

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 19, 2009
• First Posted: January 21, 2009
• Study Start: January 1, 2009
• Primary Completion: November 1, 2011
• Study Completion: November 1, 2011
• Last Updated: December 24, 2020

Record last verified: 2013-02

Locations

US (7)