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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01213836
First received: October 1, 2010
Last updated: June 21, 2012
Last verified: May 2012
  Purpose

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.


Condition Intervention Phase
Schizophrenia
Drug: Seroquel XR- quetiapine fumarate extended release
Drug: Seroquel IR - quetiapine fumarate
Drug: Placebo matching Seroquel XR
Drug: Placebo matching Seroquel IR
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Mean for Attentional Standardised Composite Score Based on Performance Scores From the CogState Test Battery Domains Detection (Speed of Processing)and Identification (Attention/Vigilance) [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Mean Treatment Satisfaction for Treatment Satisfaction Questionnaire of Medication (TSQM) [ Time Frame: Before taking study drug, end of Period 1 and end of Period 2 ] [ Designated as safety issue: No ]

    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.


  • Mean Daytime Cognitive Performance Using CogState: - Working Memory - Verbal Learning) -Reasoning and Problem Solving [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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.

  • Mean Overall Sedation as Measured by the Modified Bond-Lader Visual Analogue Scale (VAS) When Administered According to Label [ Time Frame: 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. ] [ Designated as safety issue: No ]

    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.


  • Mean Overall Sedation as Measured by the Stanford Sleepiness Scale When Administered According to Label [ Time Frame: 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. ] [ Designated as safety issue: No ]

    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.


  • Number of Dropouts. [ Time Frame: Period 1 and Period 2 ] [ Designated as safety issue: No ]
    The number of patients who dropped out was counted.

  • 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. [ Time Frame: End of Period 1, end of Period 2 ] [ Designated as safety issue: No ]
    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.


Enrollment: 75
Study Start Date: November 2010
Study Completion Date: August 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  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: NCT01213836

Locations
Austria
Research Site
Wien, Austria
Denmark
Research Site
Middelfart, Denmark
Germany
Research Site
Berlin, Germany
Research Site
Bochum, Germany
Research Site
Hamburg, Germany
Research Site
Munchen, Germany
Research Site
Rottweil, Germany
Italy
Research Site
Giarre, CT, Italy
Research Site
Genova, GE, Italy
Research Site
Lido Di Camaiore, LU, Italy
Research Site
Barakaldo (vizcaya), Pais Vasco, Italy
Research Site
Tivoli, RM, Italy
Research Site
Sant'arsenio, SA, Italy
Research Site
Sassari, SS, Italy
Research Site
Borgomanero, Italy
Research Site
Catania, Italy
Research Site
Roma, Italy
Research Site
Torre Annunziata, Italy
Spain
Research Site
Salamanca, Castilla Leon, Spain
Research Site
Zamora, Castilla Leon, Spain
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Eva Dencker Vansvik AstraZeneca
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01213836     History of Changes
Other Study ID Numbers: D1443L00082, 2010-020579-21
Study First Received: October 1, 2010
Results First Received: May 15, 2012
Last Updated: June 21, 2012
Health Authority: Austria: Agency for Health and Food Safety
Germany: Federal Institute for Drugs and Medical Devices
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Spain: Spanish Agency of Medicines

Keywords provided by AstraZeneca:
Stable schizophrenia
cognitive functioning

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Quetiapine
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs

ClinicalTrials.gov processed this record on August 20, 2014