Back to resultsCompare the Effect on Cognitive Functioning of Two Formulations of Seroquel, Seroquel XR and IR in Patients With Stable Schizophrenia (eXtRa)
Primary Purpose
Schizophrenia
Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Seroquel XR- quetiapine fumarate extended release
Seroquel IR - quetiapine fumarate
Placebo matching Seroquel XR
Placebo matching Seroquel IR
Sponsored by
About this trial
This is an interventional treatment trial for Schizophrenia focused on measuring Stable schizophrenia, cognitive functioning
Eligibility 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)
Sites / Locations
- Research Site
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Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
First Seroquel XR then Seroquel IR
First Seroquel IR then Seroquel XR
Arm Description
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
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
Outcomes
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)
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)
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
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
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
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01213836
Brief Title
Compare the Effect on Cognitive Functioning of Two Formulations of Seroquel, Seroquel XR and IR in Patients With Stable Schizophrenia
Acronym
eXtRa
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2012
Overall Recruitment Status
Completed
Study Start Date
November 2010 (undefined)
Primary Completion Date
August 2011 (Actual)
Study Completion Date
August 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia
Keywords
Stable schizophrenia, cognitive functioning
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
75 (Actual)
8. Arms, Groups, and Interventions
Arm Title
First Seroquel XR then Seroquel IR
Arm Type
Active Comparator
Arm Description
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
Arm Title
First Seroquel IR then Seroquel XR
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Seroquel XR- quetiapine fumarate extended release
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Seroquel IR - quetiapine fumarate
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo matching Seroquel XR
Intervention Description
Placebo matching Seroquel XR dose 400-700 mg (in tablet form). Dose taken once a day for 10-16 days.
Intervention Type
Drug
Intervention Name(s)
Placebo matching Seroquel IR
Intervention Description
Placebo matching Seroquel IR dose 400-700 mg (in tablet form). Dose taken twice a day for 10-16 days.
Primary Outcome Measure Information:
Title
Mean for Attentional Standardised Composite Score Based on Performance Scores From the CogState Test Battery Domains Detection (Speed of Processing)and Identification (Attention/Vigilance)
Description
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.
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.
Secondary Outcome Measure Information:
Title
Mean Treatment Satisfaction for Treatment Satisfaction Questionnaire of Medication (TSQM)
Description
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.
Time Frame
Before taking study drug, end of Period 1 and end of Period 2
Title
Mean Daytime Cognitive Performance Using CogState: - Working Memory - Verbal Learning) -Reasoning and Problem Solving
Description
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.
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.
Title
Mean Overall Sedation as Measured by the Modified Bond-Lader Visual Analogue Scale (VAS) When Administered According to Label
Description
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.
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.
Title
Mean Overall Sedation as Measured by the Stanford Sleepiness Scale When Administered According to Label
Description
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.
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.
Title
Number of Dropouts.
Description
The number of patients who dropped out was counted.
Time Frame
Period 1 and Period 2
Title
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.
Description
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.
Time Frame
End of Period 1, end of Period 2
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eva Dencker Vansvik
Organizational Affiliation
AstraZeneca
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Wien
Country
Austria
Facility Name
Research Site
City
Middelfart
Country
Denmark
Facility Name
Research Site
City
Berlin
Country
Germany
Facility Name
Research Site
City
Bochum
Country
Germany
Facility Name
Research Site
City
Hamburg
Country
Germany
Facility Name
Research Site
City
Munchen
Country
Germany
Facility Name
Research Site
City
Rottweil
Country
Germany
Facility Name
Research Site
City
Giarre
State/Province
CT
Country
Italy
Facility Name
Research Site
City
Genova
State/Province
GE
Country
Italy
Facility Name
Research Site
City
Lido Di Camaiore
State/Province
LU
Country
Italy
Facility Name
Research Site
City
Barakaldo (vizcaya)
State/Province
Pais Vasco
Country
Italy
Facility Name
Research Site
City
Tivoli
State/Province
RM
Country
Italy
Facility Name
Research Site
City
Sant'arsenio
State/Province
SA
Country
Italy
Facility Name
Research Site
City
Sassari
State/Province
SS
Country
Italy
Facility Name
Research Site
City
Borgomanero
Country
Italy
Facility Name
Research Site
City
Catania
Country
Italy
Facility Name
Research Site
City
Roma
Country
Italy
Facility Name
Research Site
City
Torre Annunziata
Country
Italy
Facility Name
Research Site
City
Salamanca
State/Province
Castilla Leon
Country
Spain
Facility Name
Research Site
City
Zamora
State/Province
Castilla Leon
Country
Spain
12. IPD Sharing Statement
Learn more about this trial
Compare the Effect on Cognitive Functioning of Two Formulations of Seroquel, Seroquel XR and IR in Patients With Stable Schizophrenia
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