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

A 6-Week, Multi-centre, Double-blind, Double-dummy, Chlorpromazine-Controlled Randomised Study to Evaluate the Efficacy and Safety of Quetiapine Fumarate Extended-Release in the Treatment of Schizophrenic Patients With Acute Episode

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00882518

Acronym

ESPRIT

Enrollment

388

Registered

2009-04-16

Start date

2009-04-30

Completion date

2010-07-31

Last updated

2012-05-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Schizophrenia

Keywords

Quetiapine Fumarate (SEROQUEL) Extended-Release (XR), qualified PANSS assessment

Brief summary

The primary objective of this study is to evaluate the efficacy of quetiapine fumarate extended-release (XR) used as mono-therapy, administered once daily, in the treatment of schizophrenic patient with acute episode.

Interventions

DRUGQuetiapine Fumarate (SEROQUEL) Extended-Release (XR)

200 mg or 300 mg, oral, single dose

DRUGChlorpromazine

50 mg, oral, double dose

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Inclusion criteria

* Schizophrenia diagnosis * Provision of written informed consent before initiation of any study

Exclusion criteria

* AIDS and hepatitis B * History of seizure disorder * Hospitalisation for schizophrenic more than 1 month immediately before enter into study

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline of the Positive and Negative Syndrome Scale (PANSS) Total Score at the End of Treatment at Day 42	Baseline and 6 weeks	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.

Secondary

Measure	Time frame	Description
Change From Baseline in PANSS Negative Subscale Score at the End of Treatment at Day 42	Baseline and 6 weeks	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.
Change From Baseline in PANSS General Psychopathological Subscale Score at the End of Treatment at Day 42	Baseline and 6 weeks	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.
Change From Baseline in PANSS Aggression, Hostility Clusters Score at the End of Treatment at Day 42	Baseline and 6 weeks	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
Change From Baseline in PANSS Positive Subscale Score at the End of Treatment at Day 42	Baseline and 6 weeks	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.
Number of Patients Achieving a Reduction of at Least 30% From Baseline PANSS Total Score at the End of Treatment at Day 42	Baseline and 6 weeks	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.
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	Baseline and 6 weeks	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.)
Change in the CGI Severity of Illness Score From Baseline at the End of Treatment at Day 42	Baseline and 6 weeks	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.
Change From Baseline in PANSS Depression Clusters Score at the End of Treatment at Day 42	Baseline and 6 weeks	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

Countries

China

Participant flow

Pre-assignment details

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

Participants by arm

Arm	Count
Seroquel_XR 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	194
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. Full analysis set (FAS) population used for baseline characteristics	190
Total	384

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	9	18
Overall Study	Allocating random number by mistake	0	1
Overall Study	Central lab closure for National day	1	0
Overall Study	Incorrect enrolment	4	2
Overall Study	Lack of Efficacy	12	9
Overall Study	Severe non-compliance to protocol	3	1
Overall Study	Withdrawal by Subject	9	13

Baseline characteristics

Characteristic	Seroquel_XR	Chlorpromazine	Total
Age Continuous age	32.9 years STANDARD_DEVIATION 10.7	32.0 years STANDARD_DEVIATION 10.33	32.5 years STANDARD_DEVIATION 10.52
Sex: Female, Male Female	102 Participants	100 Participants	202 Participants
Sex: Female, Male Male	92 Participants	90 Participants	182 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	142 / 196	166 / 192
serious Total, serious adverse events	0 / 196	2 / 192

Outcome results

Primary

Change From Baseline of the Positive and Negative Syndrome Scale (PANSS) Total Score at the End of Treatment at Day 42

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.