Pharmacodynamic/Pharmacokinetic Study of AQW051 in Schizophrenia

Novartis

Status and phase: Completed; Phase 2; Phase 1

Conditions: Schizophrenia

Treatments: Drug: Placebo; Drug: AQW051

Study type: Interventional

Funder types: Industry

Identifiers

NCT00825539

CAQW051A2202

Details and patient eligibility

About

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.

Enrollment: 68 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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68 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Treatment:

Drug: Placebo

AQW051

Experimental group

Treatment:

Drug: AQW051