| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Major Depressive Disorder (MDD). |
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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 the treatment of patients with MDD as assessed by change in randomisation to Week 8 in the MADRS total score.
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| E.2.2 | Secondary objectives of the trial |
1. To evaluate if quetiapine SR improves the health related quality of life of patients with MDD, compared with placebo.
2. To evaluate the efficacy of quetiapine SR compared with escitalopram in the treatment of patients with MDD.
3. To evaluate if quetiapine SR reduces anxiety symptoms in patients with MDD, compared with placebo.
4. To evaluate if quetiapine SR improves sleep quality in patients with MDD, compared with placebo.
5. To evaluate if quetiapine SR is effective in reducing suicidal ideation in patients with MDD, compared with placebo.
6. To evaluate if quetiapine SR improves somatic anxiety symptoms in the treatment of patients with MDD, compared with placebo.
7. To evaluate if quetiapine SR improves satisfaction with medication in patients with MDD, compared with placebo.
8. To evaluate the safety and tolerability of quetiapine SR compared with placebo in the treatment of patients with MDD.
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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, inclusive.
3. Documented clinical diagnosis meeting criteria from the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) for any of the following; 296.2x Major Depressive Disorder, Single Episode, or 296.3x Major Depressive Disorder, Recurrent, as confirmed by the MINI.
4. HAM-D (17-item) total score of ≥22 and HAM-D Item 1 (depressed mood) score ≥2 both at enrolment and randomisation (Visit 2).
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 psychiatric status.
3. Patients whose current episode of depression exceeds 12 months or is less than 4 weeks from enrolment.
4. History of in-adequate 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. Patients with a positive UTS for a drug(s) legally available by prescription, must provide evidence of prescription for the drug(s).
6. Use of drugs that induce or inhibit the hepatic metabolizing cytochrome P450 3A4 enzymes within 2 weeks prior to randomisation.
7. Pregnancy or lactation.
8. 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).
9. A clinical finding that is unstable (e.g. hypertension, poorly controlled diabetes, unstable angina) or that, in the opinion of the investigator, would be negatively affected by the study medication or that would affect the study medication.
10. Conditions that could affect absorption and metabolism of study medication (e.g. malabsorption syndrome, liver disease).
11. A current diagnosis of cancer (except basal or squamous cell skin carcinoma), unless in remission for at least 5 years.
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 randomisation.
15. Use of antipsychotic, mood stabiliser, or antidepressant drugs within 7 days before randomisation, or use of fluoxetine within 28 days before randomisation, or use of MAOIs, anxiolytic or hypnotics within 14 days before randomisation (with the exception of those allowed with restriction per protocol), or use of a depot antipsychotic injection within 2 dosing interval before randomisation.
16. Patients who in the investigators opinion will require psychotherapy (other then supportive psychotherapy) during the study period, unless psychotherapy has been ongoing for a minimum of 3 months prior to randomisation.
17. Patients who, in the investigator’s judgment pose a current serious suicidal or homicidal risk, have a HAM-D Item 3 score of 3 or greater, or have made a suicide attempt within the past 6 months.
18. A patient with Diabetes Mellitus (DM).
19. Clinically significant deviation from the reference range in clinical laboratory test results as judged by the investigator.
20. An absolute neutrophil count (ANC) of less than or equal to 1.5 x 109 per liter.
21. 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.
22. Liver Function Tests AST or ALT three times the upper normal limit.
23. ECG results considered being clinically significant as determined by the investigator based on assessment by a centrally located experienced cardiologist interpreting the ECG.
24. Use of quetiapine in doses ≤25 mg/day for insomnia within 7 days before randomisation.
25. Known history of intolerance or hypersensitivity to quetiapine, escitalopram or to any other component in the tablets and capsules.
26. Known lack of response to quetiapine in the treatment of depression in a dosage of at least 50 mg per day for 4 weeks (at any time before study start), as judged by the investigator.
27. Treatment with quetiapine with a dosage of at least 50 mg/day at enrolment (visit 1).
28. Known lack of response to escitalopram in the treatment of depression in a dosage of at least 10 mg for 4 weeks (at any time before study start), as judged by the investigator.
29. Contraindications as detailed in the country-specific prescribing information for quetiapine or escitalopram.
30. Involvement in the planning and conduct of the study (applies to all AstraZeneca, investigational site staff and third party vendors).
31. Previous randomisation in the present study or any AstraZeneca- sponsored MDD study with quetiapine.
32. Participation in another clinical study or compassionate use programme within 4 weeks of randomisation or longer in accordance with local requirem.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary variable is the change from randomisation to Week 8 in the MADRS total score. |
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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) | Yes |
| E.8.2.2 | Placebo | Yes |
| 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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| End of study is defined as Database Lock (estimated as July 2007), which is the time point after which no patient will be exposed to study related activities. |
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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 | 1 |
| 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 | 2 |
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