Study Evaluating the Clinical Benefit of SEROQUEL XR in Subjects With Schizophrenia
Condition: Schizophrenia
MeSH terms: Schizophrenia
Intervention: Quetiapine Fumarate Extended- Release
Intervention description: 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 MeSH terms: Quetiapine Fumarate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 331.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Seroquel; schizophrenia; Extended Release

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).