E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Maintenance treatment of patients with Major Depressive Disorder |
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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 objective of the study is to evaluate the efficacy of quetiapine SR compared to placebo in increasing time from randomisation to a depressed event in patients with Major Depressive Disorder (MDD). |
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E.2.2 | Secondary objectives of the trial |
1. To evaluate the effect of quetiapine SR compared to placebo on health-related quality of life in patients with MDD during long-term treatment. 2. To evaluate the efficacy of quetiapine SR compared to placebo in maintaining improvement of depressive symptoms in patients with MDD during long-term treatment. 3. To evaluate the effect of quetiapine SR compared to placebo on anxiety symptoms in patients with MDD during long-term treatment. 4. To evaluate the effect of quetiapine SR compared to placebo on quality of sleep in patients with MDD during long-term treatment. 5. To evaluate the effect of quetiapine SR compared to placebo on suicidal ideation in patients with MDD during long-term treatment. 6. To evaluate the effect of quetiapine SR compared to placebo on functional disability in patients with MDD during long-term treatment. 7. To evaluate whether quetiapine SR compared to placebo is safe and well-tolerated in patients with MDD during long-term treatment. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Provision of written informed consent before initiation of any study- related procedures. 2. Men and women aged 18 to 65 years. 3. A documented clinical diagnosis according to the DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th edition) meeting criteria 296.2x Major Depressive Disorder, Single Episode, or 296.3x Major Depressive Disorder, Recurrent. 4. HAM-D(17-item) total score of ≥20 and HAM-D-17 item 1 (depressed mood) score of ≥2 at enrolment. 5. 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. 6. Be able to understand and comply with the requirements of the study, as judged by the investigator. 7. Outpatient status at enrolment. |
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E.4 | Principal exclusion criteria |
1.Patients with a DSM-IV Axis I disorder other than MDD within 6 months of enrolment. 2.Patients with a diagnosis of DSM-IV Axis II disorder which has a major impact on the patient's current pschiatric status. 3.Patients whose current episode of depression exceeds 12 months or is less than 4 weeks from enrolment. 4.History of inadequate response to an adequate treatment (6 weeks) with 2 or more classes of antidepressants during current depressive episode. 5.Substance or alcohol abuse or dependence within 6 months prior to enrolment (except dependence in full remission, and except for caffeine or nicotine dependence), as defined in DSM-IV criteria. 6.Use of drugs that induce or inhibit the hepatic metabolising cytochrome 3A4 enzymes within 14 days prior to the Open-label Run-in Treatment Period (Visit 2). 7.Evidence of clinically relevant disease (e.g. renal or hepatic impairment, significant coronary artery disease, cerebrovascular disease, viral hepatitis B or C, acquired immunodeficiency syndrome [AIDS]), or a clinical finding that is unstable or that, in the opinion of the investigator, would be negatively affected by the study medication or that would affect the study medication. 8.A clinical finding that is unstable. 9.Conditions that could affect absorption and metabolism of study medication. 10.Laboratory values for alanine aminotransferase (ALT) or aspartate aminotransferase (AST) that are 3 times the upper limit of normal. 11.A current diagnosis of cancer, unless in remission (except basal or squamous cell skin carcinoma). 12.Current or past diagnosis of stroke or Transient Ischemic Attacks (TIA). 13.History of seizure disorder, except febrile convulsions. 14.Receipt of electroconvulsive therapy (ECT) within 90 days prior to enrolment. 15.Use of antipsychotic, mood stabiliser, anticonvulsant or antidepressant drugs within 7 days before Open-label Run-in Treatment. 16.Use of quetiapine at a dose of 50mg/day or greater at enrolment. 17.Use of quetiapine for insomnia at a dose of 25mg/day or greater. 18.Patients who, in the investigators opinion will require psychotherapy (other than supportive psychotherapy) during the study period, unless psychotherapy has been ongoing for a minimum of 3 months prior to enrolment. 19.Patients who, in the investigator’s judgment, pose a current serious suicidal or homicidal risk, have a HAM-D-17 item 3 score of 3 or greater, or have made a suicide attempt within the past 6 months. 20.A patient with Diabetes Mellitus (DM). 21.Clinically significant deviation from the reference range in clinical laboratory test results as judged by the investigator. 22.An ANC (absolute neutrophil count) of less than 1.5 x 109 per liter. 23.A thyroid-stimulating hormone (TSH) concentration more 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. 24.ECG results considered clinically significant as determined by the investigator based on assessment by a centrally located experienced cardiologist interpreting the ECG. 25.Known history of intolerance or hypersensitivity to quetiapine or to any other component in the tablet. 26.Previous enrolment in the present study or randomisation in any AZ sponsored MDD study.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective of the study is to evaluate the efficacy of quetiapine SR compared to placebo in increasing time from randomisation to a depressed event in patients with MDD. A depressed event is defined as fulfilling at least one of the following: (a) Initiation of pharmacological treatment by the investigator, other than the allowed hypnotics, to treat depressive symptoms, (b) Initiation of pharmacological treatment by the patient for at least one week, other than the allowed hypnotics, to treat depressive symptoms, (c) Hospitalisation for depressive symptoms, (d) Montgomery- Åsberg Depression Rating Scale (MADRS) score greater or equal to 18 at 2 consecutive assessments or at the final assessment if the patient discontinues, (e) CGI-S score of ≥5 or (f) Suicide attempt. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
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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In order to ensure a power of 85% for the primary endpoint, 101 depressed events are required in the quetiapine SR and placebo groups. As soon as 101 depressed events have occurred, an end of study final visit will be conducted for all ongoing patients. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |