| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
The primary objectives is to demonstrate that the efficacy of the sustained release formulation (SR) of quetiapine is not inferior to the immediate release formulation (IR).
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| E.2.2 | Secondary objectives of the trial |
Secondary objectives : Secondary efficacy objectives of the study are:
1. to document maintained efficacy of quetiapine when switching from IR treatment to SR treatment, by evaluating clinical symptoms in patients with schizophrenia as assessed by the change in PANSS total score from randomization to week 6
2. The document maintained stability in PANSS positive, negative and general psychopathology symptom subscales scores respectively from randomization to week 6
3. to document maintained stability of clinical global status when switching from quetiapine IR treatment to SR treatment by evaluation of the proportion of patients with a CGI (Clinical Global Impression) Improvement score less than or equal to 4 at week 6
Secondary safety objective of the study is to document maintained safety/tolerability when switching from quetiapine IR treatment to SR treatment. |
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| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
Run-in period
For inclusion in the study run-in period patients must fulfill all of the following criteria:
1. Provision of written informed consent. Patients who are deemed incapable of providing informed consent may be enrolled if the written informed consent has been obtained from the patients Legally Authorised Representative. Inclusion in the genetic part of the study is under provision of a written informed consent separate from the main study.
2. Female and male age more than or equal to 18 and less than or equal to 65 years
3. 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
undifferentiated 295.90
4. Clinically stable, ie a CGI-Severity of illness score less than or equal to 3 within 4 weeks prior to the enrolment visit (Visit 1).
5. A stable dose of quetiapine IR between 300 and 800 mg/day within 4 weeks prior to the enrolment visit (Visit 1) as judged by the Investigator.
6. Female patients of childbearing potential must have a negative serum pregnancy test at enrolment and be willing to use a reliable method of birth control, i.e., barrier method, oral contraceptive, implant, dermal contraception, long-term injectable contraceptive, intrauterine device, or tubal ligation during the study.
7. Be able to understand and comply with the requirements of the study, as judged by the investigator.
Treatment period
In addition to fulfillment of the inclusion criteria for the run-in period the patients must fulfill all of the following criteria for entry to the treatment period
1. Clinically stable during the 4-week run in period, ie CGI-Severity of illness score less than or equal to 3 with no changes from enrollment (Visit 1) to randomization (Visit 2).
2. Receiving a stable dose of 400, 600 or 800 mg/day quetiapine IR during the 4 week run-in period, ie receiving the same dose throughout the run-in period
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| E.4 | Principal exclusion criteria |
Any of the following is regarded as a criterion for exclusion from the study:
1. Meeting the criteria for any other (than schizophrenia) DSM IV Axis I diagnosis, concomitant organic mental disorder or mental retardation.
2. Patients with substance abuse or dependence as defined by DSM-IV and not in full remission. A urine drug screen test will be performed. The investigator will evaluate the results along with medical history to determine if the patient meets DSM-IV criteria for substance abuse or dependence.
3. Risk of transmitting human immunodeficiency virus (HIV) or hepatitis B, via blood or other body fluids as judged by the investigator.
4. Patients who, in the opinion of the investigator, pose an imminent risk of suicide or a danger to self or others.
5. History of non-compliance as judged by the investigator.
6. Evidence of clinically relevant disease, (eg, renal or hepatic impairment, significant coronary artery disease, 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 investigator, would be negatively affected by the investigational product or that would affect the investigational product
7. Clinically significant deviation from the reference range in clinical laboratory test results at enrolment as judged by the investigator.
8. ECG considered to show cardiac abnormality at enrolment as determined by a central reader cardiologist and confirmed by Investigator as clinically significant.
9. A patient with Diabetes Mellitus (DM) fulfilling one of the following criteria:
- unstable DM defined as enrolment glycosylated Hb >8.5%
- 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 last 4 weeks prior to enrolment. For thiazolidinediones (glitazones) this period should not be less than 8 weeks
- taking insulin whose daily dose on one occasion has been more than 10% above or below their mean dose in the 4 weeks preceding enrolment
Note: If a diabetic patient meets one of these criteria the patient is to be excluded even if the treating physician believes that the patient is stable and can participate in the study.
10. A thyroid-stimulating hormone (TSH) concentration higher than 10% above the upper limit of the normal range of the laboratory used for sample analysis at enrolment, whether or not the patient is being treated for hypothyroidism.
11. Administration of a depot antipsychotic injection within 1 dosing interval (for the depot) before enrolment.
12. Use of any other antipsychotic within 4 weeks prior to enrolment.
13. Treatment with antidepressants, anxiolytics, hypnotics, mood stabilizers or other psychoactive drugs use compounds started within 2 weeks prior to enrolment. If treatment was started at least two weeks before enrolment, inclusion is allowed if the dose is intended to be maintained on the same stable dose level throughout the run-in period as well as during the treatment period.
14. Patients who have started treatment within 4 weeks prior to enrolment with compounds that could potentially affect the metabolism of quetiapine (drugs that induce, or inhibit the hepatic metabolizing cytochrome 3A4 enzymes, eg, inducers: phenytoin, carbamazepine, pentobarbital, rifampin, rifabutin, glucocorticoids, thioridazine, St. John's Wort. inhibitors: ketoconazole (except for topical use), itraconazole, fluconazole, erythromycin, clarithromycin, fluvoxamine, nefazodone, troleandomycin, indinavir, nelfinavir, ritonavir, and saquinavir). If treatment was started at least two weeks before enrolment, inclusion is allowed if the dose is intended to be maintained on the same stable dose level throughout the run-in period as well as during the treatment period.
15. Participation in another drug study within 4 weeks prior to enrolment into this study, or longer in accordance with local requirements.
16. Previous participation in this study.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| The proportion of patients who discontinue study treatment due to lack of efficacy, or whose PANSS total score increase 20% or more from randomisation at any visit. |
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Information not present in EudraCT |
| E.6.2 | Prophylaxis | Information not present in EudraCT |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Information not present in EudraCT |
| E.6.7 | Pharmacodynamic | Information not present in EudraCT |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | Information not present in EudraCT |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Information not present in EudraCT |
| E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
| E.6.13 | Others | Information not present in EudraCT |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Information not present in EudraCT |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 3 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 3 |
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