E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of severely depressed patients |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012378 |
E.1.2 | Term | Depression |
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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 show superiority of duloxetine 120 mg over duloxetine 60 mg in patients hospitalized for severe depression after 4 weeks of treatment. |
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E.2.2 | Secondary objectives of the trial |
Other objectives are to evaluate the rescue option in non-responding patients and the safety of duloxetine. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female patients of ≥ 18 years of age that meet criteria for severe Major Depressive Disorder, without psychotic features (according to DSM-IV and confirmed by MINI). 2. With a total score MADRS ≥ 30 and HAMD-6 ≥ 12 and CGI-Severity ≥ 4 at both screening and baseline. 3. Patients willing and able to comply with the requirement for hospitalization (at least up to visit 4) and with all scheduled visits, tests and procedures required by the protocol. 4. Informed consent document must be signed at screening visit, in accordance with GCP and local regulatory requirements, prior to any study procedure. |
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E.4 | Principal exclusion criteria |
1. Treatment resistant depression 2. Concurrent presence of any Axis I disorder other than anxiety disorders (with exception of the Obsessive-Compulsive Disorder) or Major Depressive Disorder; any previous diagnosis of a bipolar disorder, schizophrenia or Obsessive-Compulsive Disorder. 3. Depression with catatonic features (according to DSM IV), depression with post-partum onset, or organic mental disorders. 4. The presence of an Axis II disorder. 5. MDD with psychotic features requiring neuroleptic treatment and/or interfering with patient’s ability to provide informed consent. 6. DSM-IV-defined-history of substance abuse or dependence within the past year. 7. Positive urine screen for drug abuse. 8. Epilepsy or a history of seizure disorder or of a treatment with anticonvulsant medication for epilepsy or seizures. 9. Patients with acute liver injury or severe cirrhosis. 10. Known diagnosis of congenital galactosaemia, glucose or galactose malabsorption syndrome, or lactose deficiency. 11. Patient with a known diagnosis of raised intraocular pressure, or at known risk of acute narrow-angle glaucoma. 12. Serious medical illness or clinically significant laboratory abnormalities that, in the judgment of the investigator, are likely to require intervention/ hospitalization/ exclusion of study medication during the course of the study: cardiovascular (e.g. uncontrolled hypertension), respiratory, haematological, hepatal or gastrointestinal. End stage renal disease (estimated creatinine clearance ≤30 mL/min) and undergoing dialysis. 13. Abnormal thyroid-stimulating hormone (TSH) concentrations, based on the performing laboratory’s reference ranges. Patients must be clinically and chemically euthyroid at the time of randomization. Patients may be taking thyroid replacement therapy provided their dose is stable and their compliance is good for at least three months before the screening visit). 14. Pregnancy or breast-feeding. 15. Sexually active women of childbearing potential not using a medically approved method of birth control for at least one month prior to the screening visit and throughout the study. 16. Known hypersensitivity to Duloxetine or any of the inactive ingredients. 17. History of oversensitivity to psychotropic drugs. 18. Electro-convulsive Therapy (ECT) or Transcranial Magnetic Stimulation (TMS) within one year prior to screening and during the study. 19. Initiation or discontinuation of depression-oriented psychotherapeutic treatment within 6 weeks prior to screening visit, or planned use of such treatment at any time during the study. 20. Treatment with a monoamine oxidase inhibitor (MAOI) within 14 days prior to baseline visit or potential need to use a MAOI during the study or within 5 days after discontinuation of duloxetine, or treatment with fluoxetine within 30 days prior to baseline visit. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in the MADRS total score from baseline to week 4.
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
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 | Yes |
E.8.2.3.1 | Comparator description |
2 doses of the same compound are compared |
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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.8.5.1 | Number of sites anticipated in the EEA | 15 |
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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specified in the protocol |
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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 | 8 |
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 | 8 |