Compare the Effect on Cognitive Functioning of Two Formulations of Seroquel, Seroquel XR and IR in Patients With Stable Schizophrenia (eXtRa)

A Phase IV Prospective, Double-blind, Double-dummy, Randomised, Crossover Study to Assess the Impact on Daily Cognitive Functioning of Quetiapine Fumarate Immediate Release (Seroquel IR®) Dosed Twice Daily and Quetiapine Fumarate Extended Release (Seroquel XR®) Dosed Once Daily in the Evening in Patients With Stable Schizophrenia

This will be a phase IV 20 -32 day prospective, double blind, double-dummy, randomised crossover study that will evaluate the effect of quetiapine XR and quetiapine IR on cognitive performance in patients with schizophrenia stabilized on a single antipsychotic medication.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Seroquel XR- quetiapine fumarate extended release; Drug: Seroquel IR - quetiapine fumarate; Drug: Placebo matching Seroquel XR; Drug: Placebo matching Seroquel IR

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 4

Contacts and Locations

Study Locations

• Austria
  • Wien, Austria
    • Research Site
• Denmark
  • Middelfart, Denmark
    • Research Site
• Germany
  • Berlin, Germany
    • Research Site
  • Bochum, Germany
    • Research Site
  • Hamburg, Germany
    • Research Site
  • Munchen, Germany
    • Research Site
  • Rottweil, Germany
    • Research Site
• Italy
  • Borgomanero, Italy
    • Research Site
  • Catania, Italy
    • Research Site
  • Roma, Italy
    • Research Site
  • Torre Annunziata, Italy
    • Research Site
  • CT
    • Giarre, CT, Italy
      • Research Site
  • GE
    • Genova, GE, Italy
      • Research Site
  • LU
    • Lido Di Camaiore, LU, Italy
      • Research Site
  • Pais Vasco
    • Barakaldo (vizcaya), Pais Vasco, Italy
      • Research Site
  • RM
    • Tivoli, RM, Italy
      • Research Site
  • SA
    • Sant'arsenio, SA, Italy
      • Research Site
  • SS
    • Sassari, SS, Italy
      • Research Site
• Spain
  • Castilla Leon
    • Salamanca, Castilla Leon, Spain
      • Research Site
    • Zamora, Castilla Leon, Spain
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 48 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Provision of written informed consent prior to any study specific procedures
• Documented clinical diagnosis of schizophrenia, paranoid type, for at least 2 years before randomisation meeting the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV, American Psychiatric Association 2000) criteria of schizophrenia (DSM-IV codes 295.3) confirmed by MINI version 5.0
• Outpatient status at enrolment
• Dose of quetiapine IR or quetiapine XR unchanged during the last 56 days before randomisation

Exclusion Criteria:

• Diagnosis of any DSM-IV Axis I disorder other than those included in inclusion criteria above within 6 months before randomisation (e.g., alcohol dependence or psychoactive substance dependence not in full remission, concurrent organic mental disorder, or mental retardation [axis II diagnosis]) of a degree that may interfere with the patient's ability to co-operate.
• Previous stable use of high dosage of benzodiazepines during one year or more
• Significant neurological medical history (complicated head trauma as judged by the investigator, epilepsy, meningo-encephalitis)
• Use of the following medication:
• other antipsychotic drug than quetiapine within 28 days prior to randomisation
• a depot antipsychotic injection within two dosing intervals (for the depot) before randomisation (Visit 2)
• other psychoactive drugs within 14 days prior to randomisation (hypnotic or anxiolytic drugs, other than those allowed)
• Use of concomitant therapy likely to affect cognition, Medication prohibited 28 days prior to randomisation: benzodiazepines, amphetamines, reboxitin, atomoxinetine, buspiron, donepezil, duloxetine, galantamine, ginko biloba, memantine, methylphenidate, modafinil, rivastigmine, tacrine, smoking cessation therapy varencicline and any dosage form of nicotine replacement therapy. Medication prohibited 14 days prior to randomisation: irreversible monoamine oxidase inhibitors (MAOI), tricyclic antidepressants (TCA), biperiden, antoicholinergic agents (even if the indications are extra pyramidal symptoms or urinary symptoms)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: First Seroquel XR then Seroquel IR; Patients randomised to Seroquel XR will have treatment for 10-16 days and after that cross-over to treatment with Seroquel IR for 10-16 days	Drug: Seroquel XR- quetiapine fumarate extended release; Seroquel XR dose 400-700 mg (in tablet form). The investigator established the dosing schedule for each patient depending on the patient's dose when entering the study. The patients continued on the same dose during the study as they had prior to enrolment. Dose taken once a day for 10-16 days.; Drug: Seroquel IR - quetiapine fumarate; Seroquel IR dose 400-700 mg (in tablet form). The investigator established the dosing schedule for each patient depending on the patient's dose when entering the study. The patients continued on the same dose during the study as they had prior to enrolment. Dose taken twice a day for 10-16 days.; Drug: Placebo matching Seroquel XR; Placebo matching Seroquel XR dose 400-700 mg (in tablet form). Dose taken once a day for 10-16 days.; Drug: Placebo matching Seroquel IR; Placebo matching Seroquel IR dose 400-700 mg (in tablet form). Dose taken twice a day for 10-16 days.
Active Comparator: First Seroquel IR then Seroquel XR; Patients randomised to Seroquel IR will have treatment for 10-16 days and after that cross-over to treatment with Seroquel XR for 10-16 days	Drug: Seroquel XR- quetiapine fumarate extended release; Seroquel XR dose 400-700 mg (in tablet form). The investigator established the dosing schedule for each patient depending on the patient's dose when entering the study. The patients continued on the same dose during the study as they had prior to enrolment. Dose taken once a day for 10-16 days.; Drug: Seroquel IR - quetiapine fumarate; Seroquel IR dose 400-700 mg (in tablet form). The investigator established the dosing schedule for each patient depending on the patient's dose when entering the study. The patients continued on the same dose during the study as they had prior to enrolment. Dose taken twice a day for 10-16 days.; Drug: Placebo matching Seroquel XR; Placebo matching Seroquel XR dose 400-700 mg (in tablet form). Dose taken once a day for 10-16 days.; Drug: Placebo matching Seroquel IR; Placebo matching Seroquel IR dose 400-700 mg (in tablet form). Dose taken twice a day for 10-16 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean for Attentional Standardised Composite Score Based on Performance Scores From the CogState Test Battery Domains Detection (Speed of Processing)and Identification (Attention/Vigilance)	Attentional standardised composite score: Standardised speed of performance score. Higher Score=better performance. Score range minus infinity to plus infinity. Measured at baseline (before study drug administration) and in Period 1 at 3 visits,(post 1),(post 2),(post 3), in a 5-day (maximum 8 day) period. (Last test day not earlier than after 10 days of randomised)and in Period 2 at 3 visits,(post 1),(post 2),(post 3), in a 5-day (maximum 8 day) period. Last test day not earlier than after 10 days of crossover treatment.	Period 1 at 3 visits,(post 1),(post 2),(post 3), in a 5-day (maximum 8 day) period. Period 2 at 3 visits,(post 1),(post 2),(post 3), in a 5-day (maximum 8 day) period.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Treatment Satisfaction for Treatment Satisfaction Questionnaire of Medication (TSQM)	TSQM is a 14-item questionnaire with 4 sub-scales: effectiveness of the medication; treatment side effects; convenience of the medication; global satisfaction with the medication. Scale range 0-100 for each sub-scale, higher=greater satisfaction/milder side effects/greater convenience/greater overall satisfaction. There are 2 measurement, (after the start of taking study drug) one at end of period 1 and one at end of period 2. That is one measurement per patient per treatment. The mean of all the patients is presented, one mean value per treatment group.	Before taking study drug, end of Period 1 and end of Period 2
Mean Daytime Cognitive Performance Using CogState: - Working Memory - Verbal Learning) -Reasoning and Problem Solving	International Shopping List Task (ISLT): measures reasoning and problem solving. Min=minus infinity, max=plus infinity, higher score=better performance. Groton Maze Learning Test (GMLT): measures reasoning and problem solving. Min=minus infinity, max=plus infinity, lower score=better performance. Lower=better performance. One Back memory task (ONB: measures working memory, min=minus infinity, max=plus infinity, lower score=better performance.	Period 1 at 3 visits,(post 1),(post 2),(post 3), in a 5-day (maximum 8 day) period. Period 2 at 3 visits,(post 1),(post 2),(post 3), in a 5-day (maximum 8 day) period.
Mean Overall Sedation as Measured by the Modified Bond-Lader Visual Analogue Scale (VAS) When Administered According to Label	The modified Bond-Lader VAS: The degree of sedation was marked by the patient on a 100 mm VAS ranging between Alert (=0 mm) and Drowsy (=100 mm). The marked length in millimetres. There are 3 assessments made in each period (post 1, 2 and 3 for each period). That is three measurements per patient per treatment. The mean is an overall mean of all the recordings in all patients, one mean value per treatment group.	Period 1 at 3 visits,(post 1),(post 2),(post 3), in a 5-day (maximum 8 day) period. Period 2 at 3 visits,(post 1),(post 2),(post 3), in a 5-day (maximum 8 day) period.
Mean Overall Sedation as Measured by the Stanford Sleepiness Scale When Administered According to Label	Stanford Sleepiness Scale: The sleepiness was assessed by the patient on a 7 item rating scale ranging from 1 (Feeling active and vital) to 7 (Almost in reverie). There are 3 assessments made in each period (post 1, 2 and 3 for each period). That is three measurements per patient per treatment. The mean is an overall mean of all the recordings in all patients, one mean value per treatment group.	Period 1 at 3 visits,(post 1),(post 2),(post 3), in a 5-day (maximum 8 day) period. Period 2 at 3 visits,(post 1),(post 2),(post 3), in a 5-day (maximum 8 day) period.
Number of Dropouts.	The number of patients who dropped out was counted.	Period 1 and Period 2
Mean Ratio of Morning Plasma Concentration of Quetiapine and Nor-quetiapine for Quetiapine IR and Quetiapine XR, at Steady-state Conditions in the End of Each Treatment Period 1 and 2.	The ratio was derived as individual plasma concentration of quetiapine divided by the plasma concentration of nor-quetiapine. The mean ratio was derived for each treatment, XR and IR, respectively.	End of Period 1, end of Period 2

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Eva Dencker Vansvik, AstraZeneca

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: October 1, 2010
• First Submitted That Met QC Criteria: October 1, 2010
• First Posted (Estimate): October 4, 2010

Study Record Updates

• Last Update Posted (Estimate): July 27, 2012
• Last Update Submitted That Met QC Criteria: June 21, 2012
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Keywords: Stable schizophrenia; cognitive functioning
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Antidepressive Agents; Quetiapine Fumarate
• Other Study ID Numbers: D1443L00082; 2010-020579-21 (EudraCT Number)