Trial Outcomes & Findings for Quetiapine Extended Release Depression Symptoms (NCT NCT00640562)

NCT ID: NCT00640562

Last Updated: 2012-06-19

Results Overview

The CDSS scale is used to assess the level of depression in schizophrenia and to estimate the severity of depressive symptoms. CDSS has 9 items rated on four-point scale: 0=absent; 1=mild; 2=moderate; 3=severe. Anchor point descriptions are provided to aid differentiation between each item score. The first eight items are rated on basis of patients' responses to questions; the 9 item is based on clinician's assessment. The sum score is derived by adding the point score of all items (from 0 to 27 points); total score 4-5 is considered for minor depression and 6-7 score for major depression.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 216 participants
• Primary outcome timeframe: 12 week from baseline to last visit
• Results posted on: 2012-06-19

Participant Flow

Adult male and female patients. with a diagnosis of schizophrenia or schizoaffective disorder (according to DSM-IVTR criteria). with depressive symptoms HAM-D baseline score ≥ 20. and HAM-D item 1 score ≥2.

Participant milestones

Measure	Seroquel XR Seroquel XR dose uptitrated starting from 300 mg in the evening on day 0, then increasing to 600 mg and up to 800 mg in the following two evenings. Previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 3 onwards it was possible to adjust the Seroquel XR dose, depending on the clinical response and tolerability of the patient, within the range of 400-800 mg per day	Risperidone Risperidone dose was uptitrated starting from 1 mg bid (morning and evening) on day 0, then increasing to 2 mg bid and up to 3 mg in the following two days. As per the other arm, previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 2 onwards, it was allowed to adjust he dose of Risperidone depending on the clinical response and tolerability of the patient.
Overall Study STARTED	109	107
Overall Study COMPLETED	91	81
Overall Study NOT COMPLETED	18	26

Reasons for withdrawal

Measure	Seroquel XR Seroquel XR dose uptitrated starting from 300 mg in the evening on day 0, then increasing to 600 mg and up to 800 mg in the following two evenings. Previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 3 onwards it was possible to adjust the Seroquel XR dose, depending on the clinical response and tolerability of the patient, within the range of 400-800 mg per day	Risperidone Risperidone dose was uptitrated starting from 1 mg bid (morning and evening) on day 0, then increasing to 2 mg bid and up to 3 mg in the following two days. As per the other arm, previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 2 onwards, it was allowed to adjust he dose of Risperidone depending on the clinical response and tolerability of the patient.
Overall Study Adverse Event	8	5
Overall Study Lack of Efficacy	1	4
Overall Study Protocol Violation	2	4
Overall Study Withdrawal by Subject	6	10
Overall Study Known risperidone intolerance	0	1
Overall Study Past use of Seroquel -stopped due to AE	0	1
Overall Study Low study drug dose	0	1
Overall Study Glycosylated Hemoglobin >8	1	0

Baseline Characteristics

Quetiapine Extended Release Depression Symptoms

Baseline characteristics by cohort

Measure	Seroquel XR n=107 Participants Seroquel XR dose uptitrated starting from 300 mg in the evening on day 0, then increasing to 600 mg and up to 800 mg in the following two evenings. Previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 3 onwards it was possible to adjust the Seroquel XR dose, depending on the clinical response and tolerability of the patient, within the range of 400-800 mg per day	Risperidone n=103 Participants Risperidone dose was uptitrated starting from 1 mg bid (morning and evening) on day 0, then increasing to 2 mg bid and up to 3 mg in the following two days. As per the other arm, previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 2 onwards, it was allowed to adjust he dose of Risperidone depending on the clinical response and tolerability of the patient.	Total n=210 Participants Total of all reporting groups
Age Continuous	42.46 years STANDARD_DEVIATION 10.71 • n=5 Participants	42.08 years STANDARD_DEVIATION 11.48 • n=7 Participants	42.27 years STANDARD_DEVIATION 11.10 • n=5 Participants
Sex: Female, Male Female	51 Participants n=5 Participants	40 Participants n=7 Participants	91 Participants n=5 Participants
Sex: Female, Male Male	56 Participants n=5 Participants	63 Participants n=7 Participants	119 Participants n=5 Participants

PRIMARY outcome

Timeframe: 12 week from baseline to last visit

The CDSS scale is used to assess the level of depression in schizophrenia and to estimate the severity of depressive symptoms.

CDSS has 9 items rated on four-point scale: 0=absent; 1=mild; 2=moderate; 3=severe. Anchor point descriptions are provided to aid differentiation between each item score. The first eight items are rated on basis of patients' responses to questions; the 9 item is based on clinician's assessment.

The sum score is derived by adding the point score of all items (from 0 to 27 points); total score 4-5 is considered for minor depression and 6-7 score for major depression.

Outcome measures

Measure	Seroquel XR n=107 Participants Seroquel XR dose uptitrated starting from 300 mg in the evening on day 0, then increasing to 600 mg and up to 800 mg in the following two evenings. Previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 3 onwards it was possible to adjust the Seroquel XR dose, depending on the clinical response and tolerability of the patient, within the range of 400-800 mg per day	Risperidone n=103 Participants Risperidone dose was uptitrated starting from 1 mg bid (morning and evening) on day 0, then increasing to 2 mg bid and up to 3 mg in the following two days. As per the other arm, previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 2 onwards, it was allowed to adjust he dose of Risperidone depending on the clinical response and tolerability of the patient.
Change From Baseline to Week 12 of Calgary Depression Scale for Schizophrenia (CDSS) Score.	7.31 Score on a scale Standard Deviation 6.1 • Interval 6.1 to	5.53 Score on a scale Standard Deviation 6.4 • Interval 6.4 to

SECONDARY outcome

Timeframe: 12 weeks from baseline to last visit

21-item scale for depression. Symptoms are rated finely (on a 5-point scale: absent; doubtful or trivial; mild: moderate severe) or coarsely (on a 3- point scale: absent; doubtful or mild; obvious, distinct, or severe).Total score range 0- 66, higher values represent worse outcome.Number of participants refers to valid for efficacy per protocol. Change:total score at week 12 minus total score at baseline.

Outcome measures

Measure	Seroquel XR n=107 Participants Seroquel XR dose uptitrated starting from 300 mg in the evening on day 0, then increasing to 600 mg and up to 800 mg in the following two evenings. Previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 3 onwards it was possible to adjust the Seroquel XR dose, depending on the clinical response and tolerability of the patient, within the range of 400-800 mg per day	Risperidone n=103 Participants Risperidone dose was uptitrated starting from 1 mg bid (morning and evening) on day 0, then increasing to 2 mg bid and up to 3 mg in the following two days. As per the other arm, previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 2 onwards, it was allowed to adjust he dose of Risperidone depending on the clinical response and tolerability of the patient.
Change From Baseline to Week 12 of HAM-D Score	-29.83 Score on scale Standard Deviation 10.13	-23.02 Score on scale Standard Deviation 10.33

SECONDARY outcome

Timeframe: 12 weeks from baseline to last visit

30-item scale where each symptom is rated on a severity ranging from 1-7. Symptoms are categorized into 7 items referring to positive, 7 items referring to negative and 16 general psychotic. Total score range 30- 210, higher values represent worse outcome. Number of participants analyzed refers to valid for efficacy per protocol population.

Outcome measures

Measure	Seroquel XR n=107 Participants Seroquel XR dose uptitrated starting from 300 mg in the evening on day 0, then increasing to 600 mg and up to 800 mg in the following two evenings. Previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 3 onwards it was possible to adjust the Seroquel XR dose, depending on the clinical response and tolerability of the patient, within the range of 400-800 mg per day	Risperidone n=103 Participants Risperidone dose was uptitrated starting from 1 mg bid (morning and evening) on day 0, then increasing to 2 mg bid and up to 3 mg in the following two days. As per the other arm, previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 2 onwards, it was allowed to adjust he dose of Risperidone depending on the clinical response and tolerability of the patient.
Change From Baseline to Week 12 of PANSS Score	102.26 score on scale Standard Deviation 24.14	100.51 score on scale Standard Deviation 25.65

SECONDARY outcome

Timeframe: 12 weeks from baseline to last visit

The CGI-S subset ranges from 1 to 7 such that a score of 1 indicates "normal, not at all ill", while a score of 7 indicates "among the most extremely ill of patients". The change from start of treatment (baseline V2) in the Severity of Illness will be calculated by subtracting the score at start of treatment (baseline V2) from the following visits

Outcome measures

Measure	Seroquel XR n=107 Participants Seroquel XR dose uptitrated starting from 300 mg in the evening on day 0, then increasing to 600 mg and up to 800 mg in the following two evenings. Previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 3 onwards it was possible to adjust the Seroquel XR dose, depending on the clinical response and tolerability of the patient, within the range of 400-800 mg per day	Risperidone n=103 Participants Risperidone dose was uptitrated starting from 1 mg bid (morning and evening) on day 0, then increasing to 2 mg bid and up to 3 mg in the following two days. As per the other arm, previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 2 onwards, it was allowed to adjust he dose of Risperidone depending on the clinical response and tolerability of the patient.
- Change From Baseline to Week 12 of Clinical Global Impression (CGI- Severity of Illness) Score	-1.50 Score on scale Standard Deviation 1.33 • Interval 1.33 to	-1.04 Score on scale Standard Deviation 1.31 • Interval 1.31 to

SECONDARY outcome

Timeframe: 12week: descriptive statistic of CGI by visit and treatment

The CGI-S subset ranges from 1 to 7 such that a score of 1 indicates "normal, not at all ill", while a score of 7 indicates "among the most extremely ill of patients". The change from start of treatment (baseline V2) in the Severity of Illness will be calculated by subtracting the score at start of treatment (baseline V2) from the following visits

Outcome measures

Measure	Seroquel XR n=107 Participants Seroquel XR dose uptitrated starting from 300 mg in the evening on day 0, then increasing to 600 mg and up to 800 mg in the following two evenings. Previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 3 onwards it was possible to adjust the Seroquel XR dose, depending on the clinical response and tolerability of the patient, within the range of 400-800 mg per day	Risperidone n=103 Participants Risperidone dose was uptitrated starting from 1 mg bid (morning and evening) on day 0, then increasing to 2 mg bid and up to 3 mg in the following two days. As per the other arm, previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 2 onwards, it was allowed to adjust he dose of Risperidone depending on the clinical response and tolerability of the patient.
CGI- Global Improvement Mean Score at Week 12	91 score on a scale Standard Deviation 4.47	88 score on a scale Standard Deviation 4.55

SECONDARY outcome

Timeframe: 12 week from baseline to last visit

These items are presented as self-report statements with which the patient agrees or disagrees. Each response is scored as +1 if correct or -1 if incorrect. The final score is the grand total of the positive and negative points. A positive score means a positive subjective response. A negative total score means a negative subjective response

Outcome measures

Measure	Seroquel XR n=107 Participants Seroquel XR dose uptitrated starting from 300 mg in the evening on day 0, then increasing to 600 mg and up to 800 mg in the following two evenings. Previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 3 onwards it was possible to adjust the Seroquel XR dose, depending on the clinical response and tolerability of the patient, within the range of 400-800 mg per day	Risperidone n=103 Participants Risperidone dose was uptitrated starting from 1 mg bid (morning and evening) on day 0, then increasing to 2 mg bid and up to 3 mg in the following two days. As per the other arm, previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 2 onwards, it was allowed to adjust he dose of Risperidone depending on the clinical response and tolerability of the patient.
Change From Baseline to Week 12 of Drug Attitude Inventory 10 Item Scale (DAI 10) Score	86.38 score on scale Standard Deviation 4.12 • Interval 4.12 to	76.64 score on scale Standard Deviation 4.70 • Interval 4.7 to

SECONDARY outcome

Timeframe: 12 weeks from baseline to last visit

Extrapyramidal Side Effects (EPS) will be assessed using the Simpson-Angus Scale (SAS; Simpson GN et al 1970) . The CRF is source data for these assessments and day 0 is considered as baseline.

The SAS scale, containing 10 items, will be rated on a five-point scale where 0 is normal and 4 are severe symptoms. Min score =0, max score 40

Change from start of treatment (day 0) will be calculated as the visit score minus the score at start of treatment for each of the neurological assessments.

Outcome measures

Measure	Seroquel XR n=107 Participants Seroquel XR dose uptitrated starting from 300 mg in the evening on day 0, then increasing to 600 mg and up to 800 mg in the following two evenings. Previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 3 onwards it was possible to adjust the Seroquel XR dose, depending on the clinical response and tolerability of the patient, within the range of 400-800 mg per day	Risperidone n=103 Participants Risperidone dose was uptitrated starting from 1 mg bid (morning and evening) on day 0, then increasing to 2 mg bid and up to 3 mg in the following two days. As per the other arm, previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 2 onwards, it was allowed to adjust he dose of Risperidone depending on the clinical response and tolerability of the patient.
Change From Baseline in the Simpson Angus Scale (SAS) Total Score to Week 12 as an Indication of Neurological Side Effects Section	2.74 score on scale Standard Deviation 5.29	3.88 score on scale Standard Deviation 5.24

SECONDARY outcome

Timeframe: 12 week from baseline to last visi

Number of concomitant users of antidepressive drugs during the study; the number of participants analyzed refers to safety population, that is to overall participants excluding 6 participants who did not assume any study drug administration

Outcome measures

Measure	Seroquel XR n=107 Participants Seroquel XR dose uptitrated starting from 300 mg in the evening on day 0, then increasing to 600 mg and up to 800 mg in the following two evenings. Previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 3 onwards it was possible to adjust the Seroquel XR dose, depending on the clinical response and tolerability of the patient, within the range of 400-800 mg per day	Risperidone n=103 Participants Risperidone dose was uptitrated starting from 1 mg bid (morning and evening) on day 0, then increasing to 2 mg bid and up to 3 mg in the following two days. As per the other arm, previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 2 onwards, it was allowed to adjust he dose of Risperidone depending on the clinical response and tolerability of the patient.
Concomitant Use of Antidepressive Drugs From Baseline to Week 12	12 Participants	11 Participants

SECONDARY outcome

Timeframe: 12 week from screening visit to last visit

Plasma prolactin live was drawn prior to morning meal at the screening visit at the last visit

Outcome measures

Measure	Seroquel XR n=107 Participants Seroquel XR dose uptitrated starting from 300 mg in the evening on day 0, then increasing to 600 mg and up to 800 mg in the following two evenings. Previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 3 onwards it was possible to adjust the Seroquel XR dose, depending on the clinical response and tolerability of the patient, within the range of 400-800 mg per day	Risperidone n=103 Participants Risperidone dose was uptitrated starting from 1 mg bid (morning and evening) on day 0, then increasing to 2 mg bid and up to 3 mg in the following two days. As per the other arm, previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 2 onwards, it was allowed to adjust he dose of Risperidone depending on the clinical response and tolerability of the patient.
Change From Screening Visit to Week 12 of Prolactin Live	61.20 KG Standard Deviation 29.77 • Interval 29.77 to	90.80 KG Standard Deviation 55.78 • Interval 55.78 to

SECONDARY outcome

Timeframe: 12 week

Patient weight and height have been be collected in order to assess the Body Mass Index (BMI). The mean BMI values reported are assessed after 12 weeks of treatment.

Outcome measures

Measure	Seroquel XR n=107 Participants Seroquel XR dose uptitrated starting from 300 mg in the evening on day 0, then increasing to 600 mg and up to 800 mg in the following two evenings. Previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 3 onwards it was possible to adjust the Seroquel XR dose, depending on the clinical response and tolerability of the patient, within the range of 400-800 mg per day	Risperidone n=103 Participants Risperidone dose was uptitrated starting from 1 mg bid (morning and evening) on day 0, then increasing to 2 mg bid and up to 3 mg in the following two days. As per the other arm, previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 2 onwards, it was allowed to adjust he dose of Risperidone depending on the clinical response and tolerability of the patient.
Body Mass Index (BMI) at Week 12	29.07 Kg/m^2 Standard Deviation 6.65	28.80 Kg/m^2 Standard Deviation 5.31

SECONDARY outcome

Timeframe: Change of drug use from baseline to last visi

Number of concomitant users of antidepressive drugs during the study; the number of participants analyzed refers to ITT/safety population, that is to overall participants excluding the 6 participants who did not assume any study drug administration

Outcome measures

Measure	Seroquel XR n=107 Participants Seroquel XR dose uptitrated starting from 300 mg in the evening on day 0, then increasing to 600 mg and up to 800 mg in the following two evenings. Previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 3 onwards it was possible to adjust the Seroquel XR dose, depending on the clinical response and tolerability of the patient, within the range of 400-800 mg per day	Risperidone n=103 Participants Risperidone dose was uptitrated starting from 1 mg bid (morning and evening) on day 0, then increasing to 2 mg bid and up to 3 mg in the following two days. As per the other arm, previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 2 onwards, it was allowed to adjust he dose of Risperidone depending on the clinical response and tolerability of the patient.
Concomitant Use of Antidepressive Drugs From Baseline to Week 12	14 Participants	17 Participants

Adverse Events

Seroquel XR

Serious events: 4 serious events

Other events: 28 other events

Deaths: 0 deaths

Risperidone

Serious events: 4 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Measure	Seroquel XR n=109 participants at risk Seroquel XR dose uptitrated starting from 300 mg in the evening on day 0, then increasing to 600 mg and up to 800 mg in the following two evenings. Previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 3 onwards it was possible to adjust the Seroquel XR dose, depending on the clinical response and tolerability of the patient, within the range of 400-800 mg per day	Risperidone n=107 participants at risk Risperidone dose was uptitrated starting from 1 mg bid (morning and evening) on day 0, then increasing to 2 mg bid and up to 3 mg in the following two days. As per the other arm, previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 2 onwards, it was allowed to adjust he dose of Risperidone depending on the clinical response and tolerability of the patient.
Psychiatric disorders Disorientation	0.00% 0/109	0.93% 1/107
Psychiatric disorders Psycotic Disorder	0.00% 0/109	0.93% 1/107
Psychiatric disorders Delusion	0.00% 0/109	0.93% 1/107
Nervous system disorders Extrapiramidal Syndrome	0.00% 0/109	0.93% 1/107
Nervous system disorders Faint/Syndrome	0.92% 1/109	0.00% 0/107
Psychiatric disorders Acute Psycosis	0.92% 1/109	0.00% 0/107
Respiratory, thoracic and mediastinal disorders Acute Respiratory Failure	0.92% 1/109	0.00% 0/107
Social circumstances Social Stay Hospitalisation	0.92% 1/109	0.00% 0/107
Cardiac disorders Cardiocircolatory Arresti	0.92% 1/109	0.00% 0/107

Other adverse events

Measure	Seroquel XR n=109 participants at risk Seroquel XR dose uptitrated starting from 300 mg in the evening on day 0, then increasing to 600 mg and up to 800 mg in the following two evenings. Previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 3 onwards it was possible to adjust the Seroquel XR dose, depending on the clinical response and tolerability of the patient, within the range of 400-800 mg per day	Risperidone n=107 participants at risk Risperidone dose was uptitrated starting from 1 mg bid (morning and evening) on day 0, then increasing to 2 mg bid and up to 3 mg in the following two days. As per the other arm, previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 2 onwards, it was allowed to adjust he dose of Risperidone depending on the clinical response and tolerability of the patient.
Endocrine disorders Hyperprolactinemia	0.92% 1/109	9.3% 10/107
Gastrointestinal disorders Dry Months	4.6% 5/109	0.00% 0/107
General disorders Asthenia	2.8% 3/109	4.7% 5/107
Investigations Weight Increse	2.8% 3/109	1.9% 2/107
Nervous system disorders Sedation	4.6% 5/109	0.93% 1/107
Nervous system disorders Somnolence	5.5% 6/109	1.9% 2/107
Vascular disorders Hypotension	4.6% 5/109	0.93% 1/107

Additional Information

Gerard Lynch

AstraZeneca

Email: ClinicalTrialTransparency@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60