E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Major Depressive Disorder |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025453 |
E.1.2 | Term | Major depressive disorder NOS |
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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 |
To evaluate the efficacy of three fixed dosages of Lu AA34893 compared to placebo in the treatment of patients with MDD |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of Lu AA34893 compared to placebo during the course of treatment To evaluate the population pharmacokinetic parameters of Lu AA34893 and relevant metabolites |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
A patient, who meets all the following criteria, both at the Screening Visit and at the Baseline Visit, is eligible for inclusion in this study: 1. The patient is able to read and understand the Subject Information Sheet. 2. The patient has signed the Informed Consent Form. 3. The patient suffers from a MDE as the principal diagnosis according to DSM-IV-TR (classification code 296.xx) as assessed by the MINI. 4. The reported duration of the current Major Depressive Episode is at least 3 months. 5. The patient has a MADRS total score ≥26. 6. The patient is a man or woman, aged between 18 and 75 years (extremes included). 7. The patient is an in-patient in a psychiatric hospital or an out-patient at a psychiatric setting. 8. The patient, if female, must: − agree not to try to become pregnant during the study, AND − use adequate contraception (adequate contraception is defined as oral/systemic contraception, intrauterine device, diaphragm in combination with spermicide, or condom for male partner in combination with spermicide), OR − have had her last natural menstruation at least 24 months prior to baseline, OR − have been surgically sterilised prior to baseline, OR − have had a hysterectomy prior to baseline, OR − not be sexually active |
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E.4 | Principal exclusion criteria |
A patient who meets one or more of the following criteria at the Screening Visit and/or at the Baseline Visit, is not eligible for inclusion in this study: 1. The patient has one or more of the following conditions: − Any current psychiatric disorder established as the principal diagnosis other than MDD as defined in the DSM-IV-TR (assessed by the MINI). − Current or past history of: manic or hypomanic episode, schizophrenia or any other psychotic disorder, including major depression with psychotic features, mental retardation, organic mental disorders, or mental disorders due to a general medical condition as defined in the DSM-IV-TR. − Any substance disorder (except nicotine and caffeine) within the previous 6 months as defined in the DSM-IV-TR. − Presence or history of a clinically significant neurological disorder (including epilepsy, stroke). − Neurodegenerative disorder (Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, Huntington’s disease, etc.). − Any axis II disorder that might compromise the study. 2. The patient, in the opinion of the investigator, has a significant risk of suicide, or has a score ≥5 on item 10 (suicidal thought) of the MADRS or has made a suicide attempt in the previous 6 months. 3. The current depressive symptoms of the patient are considered by the investigator to have been resistant to two or more adequate antidepressant treatments of at least 6 weeks duration. 4. The patient has used or uses disallowed recent or concomitant medication (specified in Appendix II, Recent and Concomitant Medication), or it is anticipated that the patient will require treatment with at least one of the disallowed concomitant medications during the study. 5. The patient has received electroconvulsive therapy within 6 months prior to screening. 6. The patient is currently receiving formal cognitive or behavioural therapy, systematic psychotherapy, or plans to initiate such therapy during the study. 7. The patient has a clinically significant unstable illness, for example, hepatic impairment or renal insufficiency, or a cardiovascular, pulmonary, gastrointestinal, endocrine, neurological, infectious, neoplastic, skin and subcutaneous tissue disorders or metabolic disturbance. 8. The patient has a chronic liver disease. 9. The patient has clinically significant abnormal vital signs. 10. The patient has received venlafaxine as treatment for the current depressive episode. 11. The patient has a history of lack of response to previous adequate treatment with venlafaxine (including current episode). 12. The patient has a history of severe drug allergy or hypersensitivity, or known hypersentivity to venlafaxine. 13. The patient has an identified very high risk of a serious cardiac ventricular arrhythmia (e.g. those with a significant left ventricular dysfunction, NYHA Class III/IV), uncontrolled hypertension or recent history of myocardial infarction. 14. The patient has one or more laboratory values outside the normal range, based on the blood or urine samples taken at the Screening Visit, that are considered by the investigator to be clinically significant. 15. The patient has TSH value outside the normal range at Screening Visit. 16. The patient has a clinically significant abnormal ECG. 17. The patient has a QTc interval on the ECG above 450 ms in accordance to the Fredericia method (QTc=QT/RR0.33), a history of long QT syndrome and/or a history of hypokalaemia. 18. The patient has a disease or takes medication that, in the opinion of the investigator, may prolong the QTc interval (see Appendix II) or could interfere with the assessments of safety, tolerability, or efficacy. 19. The patient has a disease or takes medication (see Appendix II) that, in the opinion of the investigator, could interfere with the assessments of safety, tolerability or efficacy. 20. The patient has been treated with any investigational medicinal product within 30 days or 5 half lives (whichever is longer) prior to screening. 21. The patient is pregnant or breast-feeding. 22. The patient, in the opinion of the investigator, is unlikely to comply with the clinical study protocol or is unsuitable for any reason. 23. The patient is a member of the site personnel or their immediate families. 24. The patient has previously participated in this study. 25. The patient has previously been exposed to Lu AA34893. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Based on FAS and observed cases (OC), the change from baseline in the MADRS total score up to week 8 will be analysed using a Mixed Model for Repeated Measurements (MMRM) with freely varying covariance structures. |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
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.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 49 |
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 | No |
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 | 0 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |