E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Major Depressive Disorder in elderly patients |
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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 | 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 compare the efficacy of duloxetine 60 mg once daily (QD) to placebo on depression after 13 weeks of double-blind treatment utilizing clinician-rated measurement of the Maier Subscale score of the Hamilton Depression Rating Scale (HAMD17) in elderly patients (≥ 65 years of age) who meet criteria for MDD as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and who have had at least one previous MDD episode |
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E.2.2 | Secondary objectives of the trial |
To compare the efficacy of duloxetine 60 mg QD to placebo after 13 weeks of double-blind treatment as measured by the mean change from baseline in the learning trial score and delayed recall score of the Verbal Learning and Recall Test (VLRT).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
[1] Are male or female outpatients at least 65 years of age. [2] Sign the informed consent document. [3] Meet criteria for major depression as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision (DSM-IV-TR) (American Psychiatric Association. 1994). [4] Have a MADRS total score of at least 20 at Visits 1 and 2. [5] Have a MMSE score of at least 20 at Visit 1. [6] Have had at least one prior episode of MDD as defined by DMS-IVTR. [7] Have a degree of understanding such that the patient can communicate intelligibly with the investigator and study coordinator. [8] Are judged to be reliable and agree to keep all appointments for clinic visits, tests, and procedures required by the protocol (including use of an automated voice response system) and are able to swallow all required medication without opening or crushing. [9] Agree not to participate in any other research trial or study while enrolled in this study. |
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E.4 | Principal exclusion criteria |
[10] Are investigator site personnel directly affiliated with the study, or are immediate family of investigator site personnel directly affiliated with the study. [11] Are employed by Lilly [12] Have received treatment with a drug within the last 30 days that has not received regulatory approval at the time of study entry. [13] Are persons who have previously completed or withdrawn from this study or any other study investigating duloxetine for the treatment of depression. [14] Have any prior history of bipolar disorder, panic disorder, psychosis, schizophrenia, or obsessive-compulsive disorder. [15] Have any current (within the past 12 months) DSM-IV-TR primary Axis I diagnosis other than MDD [16] Have moderate to severe dementia. [17] Have a mental retardation diagnosis or the presence of any other Axis II disorder that, in the judgment of the investigator would interfere with the study compliance. [18] Patients judged clinically to be at serious suicidal risk in the opinion of the investigator. [19] Have a history of substance abuse or dependence within the past 6 months (drug categories defined in the DSM-IV), excluding nicotine and caffeine. [20] Have a positive urine drug screen for any substances of abuse. [21] Lack of response of the current episode of major depression to two or more adequate courses of antidepressant therapy with an adequate medication trial defined as a score of > 3 on the Antidepressant Treatment History Form. This tool is provided to sites with the protocol. [22] Have a history of a lack of response, at any time, to an adequate trial of duloxetine for the treatment of MDD (defined as treatment with at least 60mg/day of duloxetine for a minimum of 4 weeks). [23] Have a serious medical illness or clinically significant laboratory abnormality that is not stabilized or is anticipated to require hospitalization within 6 months, in the opinion of the investigator. [24] At Visit 1 an ALT, AST, or GGT >3 times upper limit of normal (ULN), based on Study Central Laboratory reference ranges. [25] Have been diagnosed with an acute liver injury or severe cirrhosis [26] Have a prior renal transplant, current renal dialysis, or serum creatinine laboratory value > 1.5 times upper limit of normal (ULN) [27] Are taking any excluded medications within 7 days prior to Visit 2 with the exception of fluoxetine which cannot be taken within 30 days prior to Visit 2. [28] Treatment with a monoamine oxidase inhibitor (MAOI) within 14 days prior to Visit 2 or have the potential need to use an MAOI during the study or within 5 days of discontinuation of study drug. [29] Have frequent and/or severe allergic reactions to multiple medications, or known allergic reactions to any of the study drugs. [30] Known hypersensitivity to duloxetine or any of the inactive ingredients. [31] Patients with uncontrolled narrow-angle glaucoma. [32] Have abnormal thyroid-stimulating hormone (TSH) concentration. [33] Have discontinued hormone replacement therapy within the previous 3 months. [34] Have had electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS) within the past year. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The HAMD17 (Hamilton 1960, 1967) is a widely used observational rating measure of depression severity. The HAMD17 will be clinician-administered and used to assess the severity of depression and its improvement during the course of therapy. The HAMD17 total score ranges from 0 (not at all depressed) to 52 (severely depressed). |
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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 | No |
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 | 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 | 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 | 7 |
E.8.5 | The trial involves multiple Member States | No |
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 | 5 |
E.8.9.1 | In the Member State concerned days | 4 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 4 |