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

Phase 4

Completed

Conditions: Schizophrenia

Interventions: Drug: Seroquel XR- quetiapine fumarate extended release
Drug: Seroquel IR - quetiapine fumarate
Drug: Placebo matching Seroquel XR
Drug: Placebo matching Seroquel IR

Registration Number: NCT01213836

Lead Sponsor: AstraZeneca

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 75

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 & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
First Seroquel XR then Seroquel IR	Seroquel IR - quetiapine fumarate	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
First Seroquel XR then Seroquel IR	Seroquel XR- quetiapine fumarate extended release	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
First Seroquel IR then Seroquel XR	Seroquel XR- quetiapine fumarate extended release	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
First Seroquel XR then Seroquel IR	Placebo matching Seroquel XR	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
First Seroquel IR then Seroquel XR	Seroquel IR - quetiapine fumarate	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
First Seroquel IR then Seroquel XR	Placebo matching 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
First Seroquel XR then Seroquel IR	Placebo matching 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
First Seroquel IR then Seroquel XR	Placebo matching Seroquel IR	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

Primary Outcome Measures

Name	Time	Method
Mean for Attentional Standardised Composite Score Based on Performance Scores From the CogState Test Battery Domains Detection (Speed of Processing)and Identification (Attention/Vigilance)	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.	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

Name	Time	Method
Number of Dropouts.	Period 1 and Period 2	The number of patients who dropped out was counted.
Mean Treatment Satisfaction for Treatment Satisfaction Questionnaire of Medication (TSQM)	Before taking study drug, end of Period 1 and end of Period 2	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 Overall Sedation as Measured by the Modified Bond-Lader Visual Analogue Scale (VAS) When Administered According to Label	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.	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 Daytime Cognitive Performance Using CogState: - Working Memory - Verbal Learning) -Reasoning and Problem Solving	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.	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 Stanford Sleepiness Scale When Administered According to Label	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.	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.
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.	End of Period 1, end of Period 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.