Clinical trial NCT00640601: Study Evaluating the Clinical Benefit of SEROQUEL XR in Subjects With Schizophrenia
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Schizophrenia
Keywords: Seroquel
schizophrenia
Extended Release
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2008-03-21
Enrollment: 331
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

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).

Primary outcomes:
measure: 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
timeFrame: Baseline to 24 weeks (or end of study)
Secondary outcomes:
measure: Change in Clinical Global Impression-Clinical Benefit (CGI-CB) Score
timeFrame: Baseline to 24 weeks
measure: Change in Positive and Negative Syndrome Scale for Schizophrenia (PANSS) Total Score
timeFrame: Baseline to 24 weeks
measure: Change in Positive and Negative Syndrome Scale for Schizophrenia (PANSS) Positive Scale Score
timeFrame: Baseline to 24 weeks
measure: Change in Positive and Negative Syndrome Scale for Schizophrenia (PANSS) Negative Scale Score
timeFrame: Baseline to 24 weeks
measure: Change in Global Assessment Scale (GAS)
timeFrame: Baseline to 24 weeks
measure: Change in Clinical Global Impression-Severity (CGI-S) Scale
timeFrame: Baseline to 24 weeks
measure: Change in Clinical Global Impression-Improvement (CGI-I) Scale
timeFrame: Day 7 - week 24
measure: Change in Social and Occupational Functioning Assessment Scale (SOFAS)
timeFrame: Baseline to 24 weeks
measure: Change in Safety Measure: Simpson-Angus Scale (SAS)
timeFrame: Baseline to 24 weeks
measure: Change in Barnes Akathisia Rating Scale (BARS)
timeFrame: Baseline to 24 weeks
Other outcomes:
Locations:
city: Garran
country: Australia
facility: Research Site
state: Australian Capital Territory
city: Newcastle
country: Australia
facility: Research Site
state: New South Wales
city: Brisbane
country: Australia
facility: Research Site
state: Queensland
city: Meadowbrook
country: Australia
facility: Research Site
state: Queensland
city: Dandenong
country: Australia
facility: Research Site
state: Victoria
city: Calgary
country: Canada
facility: Research Site
state: Alberta
city: Claresholm
country: Canada
facility: Research Site
state: Alberta
city: Red Deer
country: Canada
facility: Research Site
state: Alberta
city: Vancouver
country: Canada
facility: Research Site
state: British Columbia
city: Victoria
country: Canada
facility: Research Site
state: British Columbia
city: Miramichi
country: Canada
facility: Research Site
state: New Brunswick
city: St John's
country: Canada
facility: Research Site
state: Newfoundland and Labrador
city: St. John's
country: Canada
facility: Research Site
state: Newfoundland and Labrador
city: Sydney
country: Canada
facility: Research Site
state: Nova Scotia
city: Belleville
country: Canada
facility: Research Site
state: Ontario
city: Brantford
country: Canada
facility: Research Site
state: Ontario
city: Chatham
country: Canada
facility: Research Site
state: Ontario
city: Cornwall
country: Canada
facility: Research Site
state: Ontario
city: London
country: Canada
facility: Research Site
state: Ontario
city: Markham
country: Canada
facility: Research Site
state: Ontario
city: Mississauga
country: Canada
facility: Research Site
state: Ontario
city: Newmarket
country: Canada
facility: Research Site
state: Ontario
city: Oakville
country: Canada
facility: Research Site
state: Ontario
city: Orleans
country: Canada
facility: Research Site
state: Ontario
city: Sudbury
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Windsor
country: Canada
facility: Research Site
state: Ontario
city: Gatineau
country: Canada
facility: Research Site
state: Quebec
city: Greenfield Park
country: Canada
facility: Research Site
state: Quebec
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Rouyn-noranda
country: Canada
facility: Research Site
state: Quebec
city: Verdun
country: Canada
facility: Research Site
state: Quebec
city: Prince Albert
country: Canada
facility: Research Site
state: Saskatchewan
city: Saskatoon
country: Canada
facility: Research Site
state: Saskatchewan
city: Quebec
country: Canada
facility: Research Site
city: HK
country: Hong Kong
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
state: Korea
Study officials:
affiliation: University of Alberta
name: Pierre Chue, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: AstraZeneca
name: Willie Early, MD
role: STUDY_CHAIR
References:
citation: Chue P, Malla A, Bouchard RH, Lessard S, Ganesan S, Stip E, Johnson S, Chen E, Ahn YM, Kim YS, Robinson G, Schweikert C, Gendron A, Eriksson H; SPECTRUM XR Study Group. The long-term clinical benefit and effectiveness of switching to once-daily quetiapine extended release in patients with schizophrenia. Curr Med Res Opin. 2013 Mar;29(3):227-39. doi: 10.1185/03007995.2012.762903. Epub 2013 Jan 22.