Trial Outcomes & Findings for Efficacy and Safety of Quetiapine Fumarate in the Treatment of Schizophrenic Patients (NCT NCT00882518)

NCT ID: NCT00882518

Last Updated: 2012-05-15

Results Overview

6 weeks minus baseline.PANSS scale is a 30-item scale where each symptom is rated on a severity scale ranging from 1-7. Total scores range 30-210 from better to worse.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

388 participants

Primary outcome timeframe

Baseline and 6 weeks

Results posted on

2012-05-15

Participant Flow

388 patients from 11 sites were randomised into Quetiapine Fumarate (SEROQUEL) Extended-Release (XR) group or chlorpromazine group.

Participant milestones

Participant milestones
Measure
Quetiapine Fumarate (SEROQUEL) Extended-Release (XR)
Quetiapine Fumarate (SEROQUEL) Extended-Release (XR) was administered orally, once daily in the evening. The initial dose was 300 mg. This dose was adjusted on Day 2 to 600 mg, from Day 3 to Day 42, the dose of Quetiapine fumarate XR could be adjusted at 400 mg/day, 600 mg/day, or 800 mg/day at the investigator's discretion.
Chlorpromazine
Chlorpromazine was administered orally, twice daily. The initial dose was 50 mg to 100 mg. This dose was adjusted on Day 2 from 100 to 200 mg, on Day 3 from 150 to 300 mg, and Day 4 from 200 to 400 mg. From Day 5, the dose of chlorpromazine could be adjusted at 300 mg/day, 400 mg/day, 500 mg/day, or 600 mg/day at the investigator's discretion.
Overall Study
STARTED
196
192
Overall Study
COMPLETED
158
148
Overall Study
NOT COMPLETED
38
44

Reasons for withdrawal

Reasons for withdrawal
Measure
Quetiapine Fumarate (SEROQUEL) Extended-Release (XR)
Quetiapine Fumarate (SEROQUEL) Extended-Release (XR) was administered orally, once daily in the evening. The initial dose was 300 mg. This dose was adjusted on Day 2 to 600 mg, from Day 3 to Day 42, the dose of Quetiapine fumarate XR could be adjusted at 400 mg/day, 600 mg/day, or 800 mg/day at the investigator's discretion.
Chlorpromazine
Chlorpromazine was administered orally, twice daily. The initial dose was 50 mg to 100 mg. This dose was adjusted on Day 2 from 100 to 200 mg, on Day 3 from 150 to 300 mg, and Day 4 from 200 to 400 mg. From Day 5, the dose of chlorpromazine could be adjusted at 300 mg/day, 400 mg/day, 500 mg/day, or 600 mg/day at the investigator's discretion.
Overall Study
Adverse Event
9
18
Overall Study
Withdrawal by Subject
9
13
Overall Study
Lack of Efficacy
12
9
Overall Study
Severe non-compliance to protocol
3
1
Overall Study
Incorrect enrolment
4
2
Overall Study
Central lab closure for National day
1
0
Overall Study
Allocating random number by mistake
0
1

Baseline Characteristics

Efficacy and Safety of Quetiapine Fumarate in the Treatment of Schizophrenic Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Seroquel_XR
n=194 Participants
Quetiapine fumarate XR was administered orally, once daily in the evening. The initial dose was 300 mg. This dose was adjusted on Day 2 to 600 mg, from Day 3 to Day 42, the dose of Quetiapine fumarate XR could be adjusted at 400 mg/day, 600 mg/day, or 800 mg/day at the investigator's discretion. Full analysis set (FAS) population used for baseline characteristics
Chlorpromazine
n=190 Participants
Chlorpromazine was administered orally, twice daily. The initial dose was 50 mg to 100 mg. This dose was adjusted on Day 2 from 100 to 200 mg, on Day 3 from 150 to 300 mg, and Day 4 from 200 to 400 mg. From Day 5, the dose of chlorpromazine could be adjusted at 300 mg/day, 400 mg/day, 500 mg/day, or 600 mg/day at the investigator's discretion. Full analysis set (FAS) population used for baseline characteristics
Total
n=384 Participants
Total of all reporting groups
Age Continuous
age
32.9 years
STANDARD_DEVIATION 10.70 • n=5 Participants
32.0 years
STANDARD_DEVIATION 10.33 • n=7 Participants
32.5 years
STANDARD_DEVIATION 10.52 • n=5 Participants
Sex: Female, Male
Female
102 Participants
n=5 Participants
100 Participants
n=7 Participants
202 Participants
n=5 Participants
Sex: Female, Male
Male
92 Participants
n=5 Participants
90 Participants
n=7 Participants
182 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 6 weeks

Population: Per-protocol population was used as the analysis set for primary outcome, because this is a non-inferior design study.

6 weeks minus baseline.PANSS scale is a 30-item scale where each symptom is rated on a severity scale ranging from 1-7. Total scores range 30-210 from better to worse.

Outcome measures

Outcome measures
Measure
Quetiapine Fumarate (SEROQUEL) Extended-Release (XR)
n=159 Participants
Quetiapine Fumarate (SEROQUEL) Extended-Release (XR) was administered orally, once daily in the evening. The initial dose was 300 mg. This dose was adjusted on Day 2 to 600 mg, from Day 3 to Day 42, the dose of Quetiapine fumarate XR could be adjusted at 400 mg/day, 600 mg/day, or 800 mg/day at the investigator's discretion.
Chlorpromazine
n=150 Participants
Chlorpromazine was administered orally, twice daily. The initial dose was 50 mg to 100 mg. This dose was adjusted on Day 2 from 100 to 200 mg, on Day 3 from 150 to 300 mg, and Day 4 from 200 to 400 mg. From Day 5, the dose of chlorpromazine could be adjusted at 300 mg/day, 400 mg/day, 500 mg/day, or 600 mg/day at the investigator's discretion.
Change From Baseline of the Positive and Negative Syndrome Scale (PANSS) Total Score at the End of Treatment at Day 42
-33.4 scores on a scale
Standard Error 1.45 • Interval 1.45 to
-35.9 scores on a scale
Standard Error 1.35 • Interval 1.35 to

SECONDARY outcome

Timeframe: Baseline and 6 weeks

Population: Full analysis set was used for secondary outcome

6 weeks minus baseline PANSS scale is a 30-item scale where each symptom is rated on a severity scale ranging from 1-7. 1 =Absent ,2 =Minimal, 3 =Mild, 4 =Moderate, 5 =Moderate severe, 6 =Severe, 7= Extreme The PANSS positive subscale score is the sum of the 7 positive item scores (ie, delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution and hostility) and ranges from 7 to 49. A negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

Outcome measures

Outcome measures
Measure
Quetiapine Fumarate (SEROQUEL) Extended-Release (XR)
n=194 Participants
Quetiapine Fumarate (SEROQUEL) Extended-Release (XR) was administered orally, once daily in the evening. The initial dose was 300 mg. This dose was adjusted on Day 2 to 600 mg, from Day 3 to Day 42, the dose of Quetiapine fumarate XR could be adjusted at 400 mg/day, 600 mg/day, or 800 mg/day at the investigator's discretion.
Chlorpromazine
n=190 Participants
Chlorpromazine was administered orally, twice daily. The initial dose was 50 mg to 100 mg. This dose was adjusted on Day 2 from 100 to 200 mg, on Day 3 from 150 to 300 mg, and Day 4 from 200 to 400 mg. From Day 5, the dose of chlorpromazine could be adjusted at 300 mg/day, 400 mg/day, 500 mg/day, or 600 mg/day at the investigator's discretion.
Change From Baseline in PANSS Positive Subscale Score at the End of Treatment at Day 42
-9.9 scores on a scale
Standard Error 0.53 • Interval 0.53 to
-11.1 scores on a scale
Standard Error 0.51 • Interval 0.51 to

SECONDARY outcome

Timeframe: Baseline and 6 weeks

Population: Full analysis set was used for secondary outcome

6 weeks minus baseline PANSS scale is a 30-item scale where each symptom is rated on a severity scale ranging from 1-7. 1 =Absent ,2 =Minimal, 3 =Mild, 4 =Moderate, 5 =Moderate severe, 6 =Severe, 7= Extreme The PANSS negative subscale score is the sum of the 7 item scores (blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking), ranges from 7 to 49. A negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

Outcome measures

Outcome measures
Measure
Quetiapine Fumarate (SEROQUEL) Extended-Release (XR)
n=194 Participants
Quetiapine Fumarate (SEROQUEL) Extended-Release (XR) was administered orally, once daily in the evening. The initial dose was 300 mg. This dose was adjusted on Day 2 to 600 mg, from Day 3 to Day 42, the dose of Quetiapine fumarate XR could be adjusted at 400 mg/day, 600 mg/day, or 800 mg/day at the investigator's discretion.
Chlorpromazine
n=190 Participants
Chlorpromazine was administered orally, twice daily. The initial dose was 50 mg to 100 mg. This dose was adjusted on Day 2 from 100 to 200 mg, on Day 3 from 150 to 300 mg, and Day 4 from 200 to 400 mg. From Day 5, the dose of chlorpromazine could be adjusted at 300 mg/day, 400 mg/day, 500 mg/day, or 600 mg/day at the investigator's discretion.
Change From Baseline in PANSS Negative Subscale Score at the End of Treatment at Day 42
-5.9 scores on a scale
Standard Error 0.5 • Interval 0.5 to
-6.7 scores on a scale
Standard Error 0.48 • Interval 0.48 to

SECONDARY outcome

Timeframe: Baseline and 6 weeks

Population: Full analysis set was used for secondary outcome

The PANSS psychopathological subscale score is the sum of 16 item scores(somatic concern, anxiety, guilt feelings, tension, mannerisms and posturing, depression, motor retardation, uncooperativeness, unusual thought content, disorientation, poor attention, lack of judgment and insight, disturbance of volition, poor impulse control, preoccupation, active social avoidance), ranges from 16 to 112. A negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

Outcome measures

Outcome measures
Measure
Quetiapine Fumarate (SEROQUEL) Extended-Release (XR)
n=194 Participants
Quetiapine Fumarate (SEROQUEL) Extended-Release (XR) was administered orally, once daily in the evening. The initial dose was 300 mg. This dose was adjusted on Day 2 to 600 mg, from Day 3 to Day 42, the dose of Quetiapine fumarate XR could be adjusted at 400 mg/day, 600 mg/day, or 800 mg/day at the investigator's discretion.
Chlorpromazine
n=190 Participants
Chlorpromazine was administered orally, twice daily. The initial dose was 50 mg to 100 mg. This dose was adjusted on Day 2 from 100 to 200 mg, on Day 3 from 150 to 300 mg, and Day 4 from 200 to 400 mg. From Day 5, the dose of chlorpromazine could be adjusted at 300 mg/day, 400 mg/day, 500 mg/day, or 600 mg/day at the investigator's discretion.
Change From Baseline in PANSS General Psychopathological Subscale Score at the End of Treatment at Day 42
-12.9 scores on a scale
Standard Error 0.74 • Interval 0.74 to
-13.9 scores on a scale
Standard Error 0.71 • Interval 0.71 to

SECONDARY outcome

Timeframe: Baseline and 6 weeks

Population: Full analysis set was used for secondary outcome

6 weeks minus baseline PANSS scale is a 30-item scale where each symptom is rated on a severity scale ranging from 1-7 (better to worse). 1 =Absent ,2 =Minimal, 3 =Mild, 4 =Moderate, 5 =Moderate severe, 6 =Severe, 7= Extreme

Outcome measures

Outcome measures
Measure
Quetiapine Fumarate (SEROQUEL) Extended-Release (XR)
n=194 Participants
Quetiapine Fumarate (SEROQUEL) Extended-Release (XR) was administered orally, once daily in the evening. The initial dose was 300 mg. This dose was adjusted on Day 2 to 600 mg, from Day 3 to Day 42, the dose of Quetiapine fumarate XR could be adjusted at 400 mg/day, 600 mg/day, or 800 mg/day at the investigator's discretion.
Chlorpromazine
n=190 Participants
Chlorpromazine was administered orally, twice daily. The initial dose was 50 mg to 100 mg. This dose was adjusted on Day 2 from 100 to 200 mg, on Day 3 from 150 to 300 mg, and Day 4 from 200 to 400 mg. From Day 5, the dose of chlorpromazine could be adjusted at 300 mg/day, 400 mg/day, 500 mg/day, or 600 mg/day at the investigator's discretion.
Change From Baseline in PANSS Aggression, Hostility Clusters Score at the End of Treatment at Day 42
-4.8 scores on a scale
Standard Error 0.33 • Interval 0.33 to
-5.4 scores on a scale
Standard Error 0.32 • Interval 0.32 to

SECONDARY outcome

Timeframe: Baseline and 6 weeks

Population: Full analysis set was used for secondary outcome

6 weeks minus baseline PANSS scale is a 30-item scale where each symptom is rated on a severity scale ranging from 1-7 (better to worse). 1 =Absent ,2 =Minimal, 3 =Mild, 4 =Moderate, 5 =Moderate severe, 6 =Severe, 7= Extreme

Outcome measures

Outcome measures
Measure
Quetiapine Fumarate (SEROQUEL) Extended-Release (XR)
n=194 Participants
Quetiapine Fumarate (SEROQUEL) Extended-Release (XR) was administered orally, once daily in the evening. The initial dose was 300 mg. This dose was adjusted on Day 2 to 600 mg, from Day 3 to Day 42, the dose of Quetiapine fumarate XR could be adjusted at 400 mg/day, 600 mg/day, or 800 mg/day at the investigator's discretion.
Chlorpromazine
n=190 Participants
Chlorpromazine was administered orally, twice daily. The initial dose was 50 mg to 100 mg. This dose was adjusted on Day 2 from 100 to 200 mg, on Day 3 from 150 to 300 mg, and Day 4 from 200 to 400 mg. From Day 5, the dose of chlorpromazine could be adjusted at 300 mg/day, 400 mg/day, 500 mg/day, or 600 mg/day at the investigator's discretion.
Change From Baseline in PANSS Depression Clusters Score at the End of Treatment at Day 42
-1.8 scores on a scale
Standard Error 0.18 • Interval 0.18 to
-1.7 scores on a scale
Standard Error 0.18 • Interval 0.18 to

SECONDARY outcome

Timeframe: Baseline and 6 weeks

Population: Full analysis set was used for secondary outcome

6 weeks minus baseline PANSS scale is a 30-item scale where each symptom is rated on a severity scale ranging from 1-7 (better to worse).Total scores range 30-210 from better to worse. 1 =Absent,2 =Minimal, 3 =Mild, 4 =Moderate, 5 =Moderate severe, 6 =Severe, 7= Extreme.

Outcome measures

Outcome measures
Measure
Quetiapine Fumarate (SEROQUEL) Extended-Release (XR)
n=194 Participants
Quetiapine Fumarate (SEROQUEL) Extended-Release (XR) was administered orally, once daily in the evening. The initial dose was 300 mg. This dose was adjusted on Day 2 to 600 mg, from Day 3 to Day 42, the dose of Quetiapine fumarate XR could be adjusted at 400 mg/day, 600 mg/day, or 800 mg/day at the investigator's discretion.
Chlorpromazine
n=190 Participants
Chlorpromazine was administered orally, twice daily. The initial dose was 50 mg to 100 mg. This dose was adjusted on Day 2 from 100 to 200 mg, on Day 3 from 150 to 300 mg, and Day 4 from 200 to 400 mg. From Day 5, the dose of chlorpromazine could be adjusted at 300 mg/day, 400 mg/day, 500 mg/day, or 600 mg/day at the investigator's discretion.
Number of Patients Achieving a Reduction of at Least 30% From Baseline PANSS Total Score at the End of Treatment at Day 42
57.7 Percentage of participants
66.3 Percentage of participants

SECONDARY outcome

Timeframe: Baseline and 6 weeks

Population: Full analysis set was used for secondary outcome

6 weeks minus baseline. The number of patients with CGI Global Improvement (CGI-I) rating at least "minimally improved" at the end of treatment at Day 42 was counted, and then got the proportion among all the patients.CGI-I is scored to rate the patient's change from baseline CGI on a seven-point scale (1="Very much improved", 7="Very much worse".)

Outcome measures

Outcome measures
Measure
Quetiapine Fumarate (SEROQUEL) Extended-Release (XR)
n=194 Participants
Quetiapine Fumarate (SEROQUEL) Extended-Release (XR) was administered orally, once daily in the evening. The initial dose was 300 mg. This dose was adjusted on Day 2 to 600 mg, from Day 3 to Day 42, the dose of Quetiapine fumarate XR could be adjusted at 400 mg/day, 600 mg/day, or 800 mg/day at the investigator's discretion.
Chlorpromazine
n=190 Participants
Chlorpromazine was administered orally, twice daily. The initial dose was 50 mg to 100 mg. This dose was adjusted on Day 2 from 100 to 200 mg, on Day 3 from 150 to 300 mg, and Day 4 from 200 to 400 mg. From Day 5, the dose of chlorpromazine could be adjusted at 300 mg/day, 400 mg/day, 500 mg/day, or 600 mg/day at the investigator's discretion.
Percentage of Patients With Clinical Global Impression (CGI) Global Improvement Rating Less Than or Equal to 3 at the End of Treatment at Day 42
87.6 percentage of participants
88.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline and 6 weeks

Population: Full analysis set was used for secondary outcome

6 weeks minus baseline The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale rating the severity of the patient's illness. The patient is assessed on severity of mental illness at the time of rating 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill.

Outcome measures

Outcome measures
Measure
Quetiapine Fumarate (SEROQUEL) Extended-Release (XR)
n=194 Participants
Quetiapine Fumarate (SEROQUEL) Extended-Release (XR) was administered orally, once daily in the evening. The initial dose was 300 mg. This dose was adjusted on Day 2 to 600 mg, from Day 3 to Day 42, the dose of Quetiapine fumarate XR could be adjusted at 400 mg/day, 600 mg/day, or 800 mg/day at the investigator's discretion.
Chlorpromazine
n=190 Participants
Chlorpromazine was administered orally, twice daily. The initial dose was 50 mg to 100 mg. This dose was adjusted on Day 2 from 100 to 200 mg, on Day 3 from 150 to 300 mg, and Day 4 from 200 to 400 mg. From Day 5, the dose of chlorpromazine could be adjusted at 300 mg/day, 400 mg/day, 500 mg/day, or 600 mg/day at the investigator's discretion.
Change in the CGI Severity of Illness Score From Baseline at the End of Treatment at Day 42
-1.8 scores on a scale
Standard Error 0.12 • Interval 0.12 to
-2.1 scores on a scale
Standard Error 0.11 • Interval 0.11 to

Adverse Events

Quetiapine Fumarate (SEROQUEL) Extended-Release (XR)

Serious events: 0 serious events
Other events: 142 other events
Deaths: 0 deaths

Chlorpromazine

Serious events: 2 serious events
Other events: 166 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Quetiapine Fumarate (SEROQUEL) Extended-Release (XR)
n=196 participants at risk
Quetiapine Fumarate (SEROQUEL) Extended-Release (XR) was administered orally, once daily in the evening. The initial dose was 300 mg. This dose was adjusted on Day 2 to 600 mg, from Day 3 to Day 42, the dose of Quetiapine fumarate XR could be adjusted at 400 mg/day, 600 mg/day, or 800 mg/day at the investigator's discretion.
Chlorpromazine
n=192 participants at risk
Chlorpromazine was administered orally, twice daily. The initial dose was 50 mg to 100 mg. This dose was adjusted on Day 2 from 100 to 200 mg, on Day 3 from 150 to 300 mg, and Day 4 from 200 to 400 mg. From Day 5, the dose of chlorpromazine could be adjusted at 300 mg/day, 400 mg/day, 500 mg/day, or 600 mg/day at the investigator's discretion.
Psychiatric disorders
Suicide Attempt
0.00%
0/196
0.52%
1/192
Nervous system disorders
Grand Mal Convulsion
0.00%
0/196
0.52%
1/192

Other adverse events

Other adverse events
Measure
Quetiapine Fumarate (SEROQUEL) Extended-Release (XR)
n=196 participants at risk
Quetiapine Fumarate (SEROQUEL) Extended-Release (XR) was administered orally, once daily in the evening. The initial dose was 300 mg. This dose was adjusted on Day 2 to 600 mg, from Day 3 to Day 42, the dose of Quetiapine fumarate XR could be adjusted at 400 mg/day, 600 mg/day, or 800 mg/day at the investigator's discretion.
Chlorpromazine
n=192 participants at risk
Chlorpromazine was administered orally, twice daily. The initial dose was 50 mg to 100 mg. This dose was adjusted on Day 2 from 100 to 200 mg, on Day 3 from 150 to 300 mg, and Day 4 from 200 to 400 mg. From Day 5, the dose of chlorpromazine could be adjusted at 300 mg/day, 400 mg/day, 500 mg/day, or 600 mg/day at the investigator's discretion.
Gastrointestinal disorders
Constipation
25.0%
49/196
16.1%
31/192
Nervous system disorders
Extrapyramidal Disorder
8.7%
17/196
30.2%
58/192
Nervous system disorders
Dizziness
14.3%
28/196
14.1%
27/192
Psychiatric disorders
Insomnia
12.8%
25/196
14.6%
28/192
Psychiatric disorders
Agitation
12.2%
24/196
10.9%
21/192
Cardiac disorders
Palpitations
6.1%
12/196
8.3%
16/192
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract infection
6.1%
12/196
7.3%
14/192
Gastrointestinal disorders
Diarrhea
5.6%
11/196
7.8%
15/192
Cardiac disorders
Tachycardia
4.6%
9/196
8.9%
17/192
Cardiac disorders
Heart rate increased
4.1%
8/196
7.8%
15/192
Cardiac disorders
Orthostatic Hypotension
2.0%
4/196
9.4%
18/192
Hepatobiliary disorders
Hepatic Function Abnormal
5.6%
11/196
4.7%
9/192
Psychiatric disorders
Somnolence
7.7%
15/196
2.1%
4/192
Respiratory, thoracic and mediastinal disorders
Nasopharyngitis
2.6%
5/196
6.8%
13/192
Nervous system disorders
Akathisia
1.5%
3/196
7.3%
14/192

Additional Information

Gerard Lynch

AstraZeneca

Results disclosure agreements

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

Restriction type: OTHER