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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00640601




Registration number
NCT00640601
Ethics application status
Date submitted
17/03/2008
Date registered
21/03/2008
Date last updated
25/06/2012

Titles & IDs
Public title
Study Evaluating the Clinical Benefit of SEROQUEL XR in Subjects With Schizophrenia
Scientific title
A Multicentre, Open-label, Prospective Long-term Study Evaluating the Clinical Benefit and Effectiveness of SEROQUEL XR® (Quetiapine Fumarate Extended-Release Tablets) in Subjects With Schizophrenia
Secondary ID [1] 0 0
D1443L00025
Universal Trial Number (UTN)
Trial acronym
SPECTRUM
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Schizophrenia 0 0
Condition category
Condition code
Mental Health 0 0 0 0
Schizophrenia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Quetiapine Fumarate Extended- Release

Treatment: Drugs: Quetiapine Fumarate Extended- Release
Open-label seroquel XR tablets: On Day 1 Patients received 300 mg, on Day 2 600 mg, on Day 3 600-800 mg and between Day 4-168 400-800 mg Seroquel XR, according to clinical judgement of investigator. Dose changes were in 200 mg fixed doses. Investigational product (IP) was supplied in open label wallet blister cards and subjects were instructed to take the IP once daily in the evening.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Subjects With Improved Clinical Benefit From Assessment of Clinical Global Impression-Clinical Benefit (CGI-CB) Scale From Baseline to Week 24 or End of Study - Proportional change in CGI-CB score The CGI-CB scale is used to evaluate investigator's global weighted impression of efficacy and interference of adverse events (AEs) from enrolment to every visit. The score ranges from 1 to 10. The lower the score the better the outcome, e.g.: a score of 1 means that there is marked therapeutic effect with no burden of AEs. A score of 10 signifies that the burden of AEs outweighs the therapeutic effect, or no therapeutic effect with high burden of AEs. A change score for each subject will be calculated by subtracting the baseline score from the visit score.
Timepoint [1] 0 0
Baseline to 24 weeks (or end of study)
Secondary outcome [1] 0 0
Change in Clinical Global Impression-Clinical Benefit (CGI-CB) Score - Numerical change in CGI-CB score. The CGI-CB scale is used to evaluate investigator's global weighted impression of efficacy and interference of adverse events (AEs) from enrolment to every visit. The score ranges from 1 to 10. The lower the score the better the outcome, e.g.: a score of 1 means that there is marked therapeutic effect with no burden of AEs. A score of 10 signifies that the burden of AEs outweighs the therapeutic effect, or no therapeutic effect with high burden of AEs. A change score for each subject will be calculated by subtracting the baseline score from the visit score.
Timepoint [1] 0 0
Baseline to 24 weeks
Secondary outcome [2] 0 0
Change in Positive and Negative Syndrome Scale for Schizophrenia (PANSS) Total Score - Change in PANSS total score which includes Positive, Negative and General psychopathology. The PANSS is a 30-item scale where each symptom is rated on a severity scale ranging from 1-7, where 1=absent, 7=extreme). Maximum total score: 210, minimum total score is 30. Seven items are referring to positive symptoms (P1-7), seven items to negative symptoms (N1-7) and 16 items to general psychopathology (G1-16). The assessment prior to start of treatment is considered the baseline assessment.
Timepoint [2] 0 0
Baseline to 24 weeks
Secondary outcome [3] 0 0
Change in Positive and Negative Syndrome Scale for Schizophrenia (PANSS) Positive Scale Score - Change in positive subscale of PANSS. This subscale calculates the sum of the scores in PANSS items P1-P7. (1=absent symptoms, 7=extreme symptoms). Maximum total score: 49, minimum total score: 7.
Timepoint [3] 0 0
Baseline to 24 weeks
Secondary outcome [4] 0 0
Change in Positive and Negative Syndrome Scale for Schizophrenia (PANSS) Negative Scale Score - Change in negative subscale of PANSS. This subscale calculates the sum of the scores in PANSS items N1-N7. (1=absent symptoms, 7=extreme symptoms). Maximum total score: 49, minimum total score: 7.
Timepoint [4] 0 0
Baseline to 24 weeks
Secondary outcome [5] 0 0
Change in Global Assessment Scale (GAS) - Change in GAS score. The GAS is a 100-point single item scale that rates patient's functioning on a hypothetical continuum of mental health to mental illness. The scale values range from 1 to 100 (1=most impaired, 100=healthiest).
Timepoint [5] 0 0
Baseline to 24 weeks
Secondary outcome [6] 0 0
Change in Clinical Global Impression-Severity (CGI-S) Scale - The CGI-S assesses severity of illness which is scored to rate the patient's current clinical state at start of treatment. The scores range from 1 to 7, where 1= normal, not at all ill, while a score of 7=among the most extremely ill of subjects. The change from start of treatment in the severity of illness is calculated by subtracting the score at start of treatment from the visit score. Alleviation of symptom severity will be indicated by a negative change score.
Timepoint [6] 0 0
Baseline to 24 weeks
Secondary outcome [7] 0 0
Change in Clinical Global Impression-Improvement (CGI-I) Scale - Change in CGI-I scale. This scale is the second part of the CGI scale that is scored at Visit 3 to week 24 to observe the patient's change from start of treatment. The scores for the CGI-I subset ranges from 1 to 7 (1=very much improved, 7=very much worse and a score of 4 indicates no change.)
Timepoint [7] 0 0
Day 7 - week 24
Secondary outcome [8] 0 0
Change in Social and Occupational Functioning Assessment Scale (SOFAS) - Change in SOFAS score. The SOFAS is a 100 point single item scale that rates functioning of a patient. The scale values range from 1=most impaired to 100=healthiest individual. The scale also includes a rating point of 0=missing information.
Timepoint [8] 0 0
Baseline to 24 weeks
Secondary outcome [9] 0 0
Change in Safety Measure: Simpson-Angus Scale (SAS) - The Percentage of patients with change in Simpson-Angus Scale (SAS)was calculated. This is a 10 item scale that is rated on a five-point scale where 0=normal and 4=severe symptoms of Extrapyramidal symptoms (EPS) with a focus on parkinsonian symptoms of EPS.
Timepoint [9] 0 0
Baseline to 24 weeks
Secondary outcome [10] 0 0
Change in Barnes Akathisia Rating Scale (BARS) - The Percentage of patients with change in BARS score was calculated. The BARS is a 4 item scale that is rating Extrapyramidal symptoms (EPS) on a 4-point scale for the first three questions and on a 6-point scale for the last question. 0=normal and a higher value represents more pronounced symptoms of EPS. BARS has a focus on the akathisia symptoms of EPS.
Timepoint [10] 0 0
Baseline to 24 weeks

Eligibility
Key inclusion criteria
- Provision of written informed consent before initiation of any study related
procedures.

- Male and female subjects aged 18 to 65 years, inclusive.

- Documented clinical diagnosis meeting the Diagnostic and Statistical Manual of Mental
Disorders, 4th edition (DSM-IV) criteria for any of the following: Schizophrenia
DSM-IV, catatonic 295.20, disorganised 295.10, paranoid 295.30 and undifferentiated
295.90.

- Outpatient status.

- Subjects who in their own and/or in the Principal Investigator's opinion, consider
their ongoing antipsychotic treatment inadequate because of insufficient efficacy,
poor tolerance, and/or non acceptability of their actual dosage regimen (eg. b.i.d,
t.i.d, etc).

- Monotherapy with current antipsychotic for at least 7 days prior to initiating
treatment (ie, cannot be on more than one antipsychotic during the 7 day period prior
to initiating study medication). Note: Subjects on a b.i.d regimen of seroquel IR for
7 days prior to enrolment are eligible to participate in the study.

- Female subjects of childbearing potential must have a negative serum pregnancy test at
enrolment and be willing to use a reliable method of birth control, ie, barrier
method, oral contraceptive, implant, dermal contraception, long-term injectable
contraceptive, intrauterine device, or tubal ligation during the study.

- Capable to make treatment decisions, including being able to understand and comply
with the requirements of the study, and judged as such by the Principal Investigator.

- Be able to read and write either English or French at a grade 7 proficiency level.
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- First episode, drug naive schizophrenic subjects.

- Meeting the criteria for any other (than schizophrenia) DSM-IV Axis I diagnosis,
concomitant organic mental disorder or mental retardation that in the opinion of the
Principal Investigator may interfere with study conduct or interpretation.

- Substance/alcohol dependence or abuse at enrolment [except dependence in full
remission (>3 months) and except caffeine and nicotine dependence] as defined by
DSM-IV criteria. A urine drug screen will be performed. The Principal Investigator
will evaluate the results along with medical history to determine if the patient meets
DSM-IV criteria for substance abuse or dependence. However, a single urine toxicology
screen for cocaine, heroin, methamphetamine or PCP will lead to exclusion.

- Subjects requiring treatment with another antipsychotic agent than investigational
product during study.

- Subjects on seroquel IR once daily.

- Known lack of response to clozapine or treatment with clozapine within 4 weeks prior
to enrolment.

- Known intolerance to seroquel IR.

- Subjects requiring treatment with disallowed medication following enrolment into the
study.

- Subjects requiring treatment for epilepsy.

- Subjects who pose an imminent risk of suicide or danger to themselves or others, as
judged by the Principal Investigator.

- Pregnancy or lactation.

- A thyroid-stimulating hormone (TSH) concentration more than 10% above the upper limit
of the normal range of the laboratory used for sample analysis whether or not the
patient is being treated for hypothyroidism or hyperthyroidism.

- Use of a depot or long-acting injectable antipsychotic drug within 1 dosing interval
before Day 1 of treatment or during treatment.

- Use of drugs that induce or inhibit the hepatic metabolising cytochrome P450 3A4
enzymes within 14 days of the screening assessment period (Day -7 to 0). See Table 5.

- History of idiopathic or drug-induced agranulocytosis.

- A QTc interval longer than 450 msec (calculated using the Fridericia correction for
heart rate) or ECG considered to show cardiac abnormality at enrolment as determined
by a centrally located, experienced cardiologist, and confirmed by the Principal
Investigator as clinically significant.

- Evidence of clinically relevant disease (eg, renal, hepatic, autonomic, endocrine,
hematologic or ophthalmologic impairment, significant coronary artery disease,
congestive heart failure, cerebrovascular disease, viral hepatitis B or C, acquired
immunodeficiency syndrome [AIDS] or cancer) or a clinical finding that is unstable or
that, in the opinion of the Principal Investigator, would be negatively affected by
the investigational product or that would affect the investigational product.

- Laboratory test results outside the reference range considered by the Principal
Investigator to be clinically significant and potentially interfere with the study
outcome.

- A patient with Diabetes Mellitus (DM) fulfilling one of the following criteria:

- Unstable DM defined as HbA1c >8.5% at enrolment. Admitted to hospital for
treatment of DM or DM related illness in past 12 weeks.

- Not under care of physician responsible for patient's DM care.

- Physician responsible for patient's DM care has not indicated that patient's DM
is controlled.

- Physician responsible for patient's DM care has not approved patient's
participation in the study.

- Has not been on the same dose of oral hypoglycemic drug(s) and/or diet for the
four (4) weeks prior to randomisation. For thiazolidinediones (glitazones) this
period should not be less than 8 weeks.

- Taking insulin whose daily dose on one occasion in the past 4 weeks has been more
than 10% above or below their mean dose in the preceding 4 weeks.

Note: If a diabetic patient meets one of these criteria the patient is to be excluded even
if the treating physician believes the patient is stable and can participate in the study.

- An absolute neutrophil count (ANC) of <1.5 x 109/L

- Inability to accommodate the visit schedule.

- History of non-compliance as judged by the Principal Investigator.

- Previous enrolment in the present study.

- Participation in another clinical study or compassionate use programme within 4 weeks
of screening (Day -7 to 0).

- Involvement in the planning and conduct of the study (applies to both AstraZeneca
staff or staff at the study site).

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,VIC
Recruitment hospital [1] 0 0
Research Site - Garran
Recruitment hospital [2] 0 0
Research Site - Newcastle
Recruitment hospital [3] 0 0
Research Site - Brisbane
Recruitment hospital [4] 0 0
Research Site - Meadowbrook
Recruitment hospital [5] 0 0
Research Site - Dandenong
Recruitment postcode(s) [1] 0 0
- Garran
Recruitment postcode(s) [2] 0 0
- Newcastle
Recruitment postcode(s) [3] 0 0
- Brisbane
Recruitment postcode(s) [4] 0 0
- Meadowbrook
Recruitment postcode(s) [5] 0 0
- Dandenong
Recruitment outside Australia
Country [1] 0 0
Canada
State/province [1] 0 0
Alberta
Country [2] 0 0
Canada
State/province [2] 0 0
British Columbia
Country [3] 0 0
Canada
State/province [3] 0 0
New Brunswick
Country [4] 0 0
Canada
State/province [4] 0 0
Newfoundland and Labrador
Country [5] 0 0
Canada
State/province [5] 0 0
Nova Scotia
Country [6] 0 0
Canada
State/province [6] 0 0
Ontario
Country [7] 0 0
Canada
State/province [7] 0 0
Quebec
Country [8] 0 0
Canada
State/province [8] 0 0
Saskatchewan
Country [9] 0 0
Hong Kong
State/province [9] 0 0
HK
Country [10] 0 0
Korea, Republic of
State/province [10] 0 0
Korea

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
A Multicentre, Open-label, Prospective Long-term Study Evaluating the Clinical Benefit and
Effectiveness of SEROQUEL XR® (Quetiapine Fumarate Extended-Release Tablets) in Subjects with
Schizophrenia.
Trial website
https://clinicaltrials.gov/show/NCT00640601
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pierre Chue, MD
Address 0 0
University of Alberta
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications