Trial Outcomes & Findings for Compare the Effect on Cognitive Functioning of Two Formulations of Seroquel, Seroquel XR and IR in Patients With Stable Schizophrenia (NCT NCT01213836)
NCT ID: NCT01213836
Last Updated: 2012-07-27
Results Overview
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.
COMPLETED
PHASE4
75 participants
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.
2012-07-27
Participant Flow
Patients were recruited at 20 study centres in 5 countries: Austria (1 site), Denmark (1 site), Germany (6 sites), Italy (9 sites) and Spain (3 sites). Recruitment started 2 November 2010 and was completed 29 June 2011. The last patient completed the study on 3 August 2011.
Screening (0 days to 14 days before enrolment), enrolment at Visit 1 (14 days to 3 days prior to randomisation), randomisation at Visit 2 after confirmation of eligibility. 75 patients were screened/enrolled. Of these, 9 were not randomised; 2 patients due to own decision to discontinue and 7 patients due to eligibility criteria not fulfilled.
Participant milestones
| Measure |
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
|
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
|
|---|---|---|
|
Period 1, First Intervention
STARTED
|
34
|
32
|
|
Period 1, First Intervention
COMPLETED
|
31
|
29
|
|
Period 1, First Intervention
NOT COMPLETED
|
3
|
3
|
|
Period 2, Second Intervention
STARTED
|
31
|
29
|
|
Period 2, Second Intervention
COMPLETED
|
31
|
29
|
|
Period 2, Second Intervention
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
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
|
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
|
|---|---|---|
|
Period 1, First Intervention
Adverse Event
|
2
|
1
|
|
Period 1, First Intervention
Protocol Violation
|
0
|
1
|
|
Period 1, First Intervention
Withdrawal by Subject
|
1
|
1
|
Baseline Characteristics
Compare the Effect on Cognitive Functioning of Two Formulations of Seroquel, Seroquel XR and IR in Patients With Stable Schizophrenia
Baseline characteristics by cohort
| Measure |
First Seroquel XR Then Seroquel IR
n=34 Participants
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
n=32 Participants
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
|
Total
n=66 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
between 18 and 29 years
|
6 participants
n=5 Participants
|
3 participants
n=7 Participants
|
9 participants
n=5 Participants
|
|
Age Continuous
Between 30 and 50 years
|
26 participants
n=5 Participants
|
28 participants
n=7 Participants
|
54 participants
n=5 Participants
|
|
Age Continuous
>50 years
|
2 participants
n=5 Participants
|
0 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Age Continuous
|
38.6 years
STANDARD_DEVIATION 8.2 • n=5 Participants
|
37.0 years
STANDARD_DEVIATION 5.2 • n=7 Participants
|
37.8 years
STANDARD_DEVIATION 6.9 • n=5 Participants
|
|
Gender
Female
|
11 participants
n=5 Participants
|
9 participants
n=7 Participants
|
20 participants
n=5 Participants
|
|
Gender
Male
|
23 participants
n=5 Participants
|
22 participants
n=7 Participants
|
45 participants
n=5 Participants
|
|
Region of Enrollment
Spain
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Region of Enrollment
Denmark
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Region of Enrollment
Austria
|
1 participants
n=5 Participants
|
2 participants
n=7 Participants
|
3 participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
18 participants
n=5 Participants
|
10 participants
n=7 Participants
|
28 participants
n=5 Participants
|
|
Region of Enrollment
Italy
|
13 participants
n=5 Participants
|
18 participants
n=7 Participants
|
31 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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.Population: The per protocol set (PPS) is a subset of the FAS consisting of patients who fulfilled all inclusion criteria but none of the exclusion criteria, complied with study medication dosing scheme, did not violate any of the study restrictions and completed the study without protocol violation.
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.
Outcome measures
| Measure |
Seroquel XR
n=51 Participants
Patients that took Seroquel XR in arm XR-IR and arm IR-XR.
|
Seroquel IR
n=51 Participants
Patients that took Seroquel XR in arm XR-IR and arm IR-XR.
|
|---|---|---|
|
Mean for Attentional Standardised Composite Score Based on Performance Scores From the CogState Test Battery Domains Detection (Speed of Processing)and Identification (Attention/Vigilance)
Post 1
|
0.002 standardised units
Standard Deviation 0.856 • Interval -0.087 to 0.098
|
-0.098 standardised units
Standard Deviation 0.983
|
|
Mean for Attentional Standardised Composite Score Based on Performance Scores From the CogState Test Battery Domains Detection (Speed of Processing)and Identification (Attention/Vigilance)
Post 2
|
-0.201 standardised units
Standard Deviation 1.054
|
-0.131 standardised units
Standard Deviation 1.053
|
|
Mean for Attentional Standardised Composite Score Based on Performance Scores From the CogState Test Battery Domains Detection (Speed of Processing)and Identification (Attention/Vigilance)
Post 3
|
-0.194 standardised units
Standard Deviation 1.040
|
-0.120 standardised units
Standard Deviation 1.100
|
SECONDARY outcome
Timeframe: Before taking study drug, end of Period 1 and end of Period 2Population: Full Analysis Set (FAS)used for efficacy analysis included all patients who in both study periods, received at least 1 dose of investigational product and for whom post-dose efficacy data was available.
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.
Outcome measures
| Measure |
Seroquel XR
n=60 Participants
Patients that took Seroquel XR in arm XR-IR and arm IR-XR.
|
Seroquel IR
n=59 Participants
Patients that took Seroquel XR in arm XR-IR and arm IR-XR.
|
|---|---|---|
|
Mean Treatment Satisfaction for Treatment Satisfaction Questionnaire of Medication (TSQM)
Side Effects
|
87.9 units on a scale
Standard Deviation 20.5
|
81.5 units on a scale
Standard Deviation 27.5
|
|
Mean Treatment Satisfaction for Treatment Satisfaction Questionnaire of Medication (TSQM)
Effectiveness
|
65.4 units on a scale
Standard Deviation 16.8
|
62.2 units on a scale
Standard Deviation 19.1
|
|
Mean Treatment Satisfaction for Treatment Satisfaction Questionnaire of Medication (TSQM)
Convenience
|
66.2 units on a scale
Standard Deviation 19.3
|
63.6 units on a scale
Standard Deviation 19.7
|
|
Mean Treatment Satisfaction for Treatment Satisfaction Questionnaire of Medication (TSQM)
Overall Satisfaction
|
63.0 units on a scale
Standard Deviation 19.7
|
58.9 units on a scale
Standard Deviation 21.1
|
SECONDARY outcome
Timeframe: 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.Population: Per Protocol (PPS), subset of the FAS consisting of patients who fulfilled all of inclusion but none of exclusion criteria, complied with study medication dosing, did not violate any of the restrictions and completed the study without protocol violation.
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.
Outcome measures
| Measure |
Seroquel XR
n=51 Participants
Patients that took Seroquel XR in arm XR-IR and arm IR-XR.
|
Seroquel IR
n=51 Participants
Patients that took Seroquel XR in arm XR-IR and arm IR-XR.
|
|---|---|---|
|
Mean Daytime Cognitive Performance Using CogState: - Working Memory - Verbal Learning) -Reasoning and Problem Solving
ISLT post 1
|
24.020 Units on a scale
Standard Deviation 5.746 • Interval -0.22 to 1.055
|
23.588 Units on a scale
Standard Deviation 5.787
|
|
Mean Daytime Cognitive Performance Using CogState: - Working Memory - Verbal Learning) -Reasoning and Problem Solving
ISLT post 2
|
23.551 Units on a scale
Standard Deviation 4.899 • Interval -2.714 to 3.791
|
23.152 Units on a scale
Standard Deviation 5.562
|
|
Mean Daytime Cognitive Performance Using CogState: - Working Memory - Verbal Learning) -Reasoning and Problem Solving
ISLT post 3
|
23.216 Units on a scale
Standard Deviation 5.360 • Interval -0.026 to 0.009
|
22.920 Units on a scale
Standard Deviation 4.944
|
|
Mean Daytime Cognitive Performance Using CogState: - Working Memory - Verbal Learning) -Reasoning and Problem Solving
GMLT post 1
|
64.180 Units on a scale
Standard Deviation 29.822
|
61.040 Units on a scale
Standard Deviation 28.721
|
|
Mean Daytime Cognitive Performance Using CogState: - Working Memory - Verbal Learning) -Reasoning and Problem Solving
GMLT post 2
|
59.021 Units on a scale
Standard Deviation 21.257
|
56.956 Units on a scale
Standard Deviation 21.798
|
|
Mean Daytime Cognitive Performance Using CogState: - Working Memory - Verbal Learning) -Reasoning and Problem Solving
GMLT post 3
|
57.229 Units on a scale
Standard Deviation 24.162
|
57.300 Units on a scale
Standard Deviation 22.307
|
|
Mean Daytime Cognitive Performance Using CogState: - Working Memory - Verbal Learning) -Reasoning and Problem Solving
ONB post 1
|
2.875 Units on a scale
Standard Deviation 0.143
|
2.897 Units on a scale
Standard Deviation 0.134
|
|
Mean Daytime Cognitive Performance Using CogState: - Working Memory - Verbal Learning) -Reasoning and Problem Solving
ONB post 2
|
2.896 Units on a scale
Standard Deviation 0.151
|
2.896 Units on a scale
Standard Deviation 0.169
|
|
Mean Daytime Cognitive Performance Using CogState: - Working Memory - Verbal Learning) -Reasoning and Problem Solving
ONB post 3
|
2.894 Units on a scale
Standard Deviation 0.161
|
2.893 Units on a scale
Standard Deviation 0.154
|
SECONDARY outcome
Timeframe: 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.Population: The full analysis set (FAS) used for analysis of efficacy included all patients who, in both study periods, received at least one dose of investigational product and for whom post-dose efficacy data are available in both periods.
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.
Outcome measures
| Measure |
Seroquel XR
n=60 Participants
Patients that took Seroquel XR in arm XR-IR and arm IR-XR.
|
Seroquel IR
n=60 Participants
Patients that took Seroquel XR in arm XR-IR and arm IR-XR.
|
|---|---|---|
|
Mean Overall Sedation as Measured by the Modified Bond-Lader Visual Analogue Scale (VAS) When Administered According to Label
|
23.5 units on a scale
Standard Deviation 19.0
|
28.6 units on a scale
Standard Deviation 21.4
|
SECONDARY outcome
Timeframe: 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.Population: The full analysis set (FAS) used for analysis of efficacy included all patients who, in both study periods, received at least one dose of investigational product and for whom post-dose efficacy data are available in both periods.
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.
Outcome measures
| Measure |
Seroquel XR
n=60 Participants
Patients that took Seroquel XR in arm XR-IR and arm IR-XR.
|
Seroquel IR
n=60 Participants
Patients that took Seroquel XR in arm XR-IR and arm IR-XR.
|
|---|---|---|
|
Mean Overall Sedation as Measured by the Stanford Sleepiness Scale When Administered According to Label
|
2.4 units on a scale
Standard Deviation 0.9
|
2.6 units on a scale
Standard Deviation 1.0
|
SECONDARY outcome
Timeframe: Period 1 and Period 2Population: The Safety analysis set was used, that is all patients who received at least one dose of study medication and for whom any post-dose safety data are available were included in the safety set.
The number of patients who dropped out was counted.
Outcome measures
| Measure |
Seroquel XR
n=34 Participants
Patients that took Seroquel XR in arm XR-IR and arm IR-XR.
|
Seroquel IR
n=31 Participants
Patients that took Seroquel XR in arm XR-IR and arm IR-XR.
|
|---|---|---|
|
Number of Dropouts.
Period 1
|
3 participants
|
2 participants
|
|
Number of Dropouts.
Period 2
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: End of Period 1, end of Period 2Population: 21 patients for the FAS were analysed. This outcome measure was introduced as a protocol amendment after study start and plasma concentration was not measured in all patients. FAS is all patients who, in both study periods, received at least one dose of investigational product and for whom post-dose efficacy data are available in both periods.
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.
Outcome measures
| Measure |
Seroquel XR
n=21 Participants
Patients that took Seroquel XR in arm XR-IR and arm IR-XR.
|
Seroquel IR
n=21 Participants
Patients that took Seroquel XR in arm XR-IR and arm IR-XR.
|
|---|---|---|
|
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.
|
1.941 Ratio
Standard Deviation 1.504
|
2.128 Ratio
Standard Deviation 2.369
|
Adverse Events
Seroquel XR
Seroquel IR
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Seroquel XR
n=63 participants at risk
Patients treated with at least one dose of Seroquel XR
|
Seroquel IR
n=62 participants at risk
Patients treated with at least one dose of Seroquel IR
|
|---|---|---|
|
Blood and lymphatic system disorders
neutropenia
|
0.00%
0/63
|
1.6%
1/62 • Number of events 1
|
|
Cardiac disorders
tachycardia
|
0.00%
0/63
|
1.6%
1/62 • Number of events 1
|
|
Ear and labyrinth disorders
vertigo
|
1.6%
1/63 • Number of events 1
|
0.00%
0/62
|
|
General disorders
fatigue
|
0.00%
0/63
|
1.6%
1/62 • Number of events 1
|
|
Investigations
heart rate increase
|
0.00%
0/63
|
1.6%
1/62 • Number of events 1
|
|
Nervous system disorders
dizziness
|
0.00%
0/63
|
1.6%
1/62 • Number of events 1
|
|
Nervous system disorders
sedation
|
1.6%
1/63 • Number of events 1
|
0.00%
0/62
|
|
Nervous system disorders
somnolence
|
1.6%
1/63 • Number of events 1
|
3.2%
2/62 • Number of events 2
|
|
Psychiatric disorders
delusion
|
0.00%
0/63
|
1.6%
1/62 • Number of events 1
|
|
Psychiatric disorders
psychotic disorder
|
1.6%
1/63 • Number of events 1
|
0.00%
0/62
|
|
Psychiatric disorders
sleep disorder
|
1.6%
1/63 • Number of events 1
|
0.00%
0/62
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60