| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Major Depressive Disorder |
|
| 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 | 10012399 |
| E.1.2 | Term | Depressive disorder |
|
| 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 this study is to compare the mean baseline to endpoint change in the Apathy Evaluation Scale – Clinician rated version (AES-C) total score in patients who have been treated with an SSRI for at least 3 months for major depressive disorder who have residual apathy (AES-C total score >30) in the absence of depressed mood (MADRS total score <15), between patients who are randomized to switch treatment toeither double-blind duloxetine 60-120 mg QD or escitalopram 10-20 mg QD for 8 weeks. |
|
| E.2.2 | Secondary objectives of the trial |
| The secondary objectives of this study are to compare duloxetine 60-120 mg QD with escitalopram 10-20 mg QD on : Longitudinal (visit-wise mean) profiles and mean changes from baseline scores of: Apathy Evaluation Scale-Clinician rated version (AES-C) subscale scores RSAT total and individual item scores PGI-Improvement Rating Scale CGI-Severity Rating Scale MADRS total score and item 8 (inability to feel) Mean changes from baseline scores of the following measures: Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (MGH-CPFQ) total and individual item scores Sheehan Disability Scale (SDS) total and individual item scores Proportion of patients who relapse and time to relapse as defined by MADRS total score >16 Proportion of patients who discontinue due to lack of efficacy To compare the safety and tolerability of duloxetine to escitalopram |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| [1] Male or female outpatients aged 18 years or older who have received treatment with an SSRI (escitalopram, sertraline, paroxetine or citalopram) for at least 3 months for major depressive disorder (MDD) based on the disease diagnostic criteria (see below). [2] Inclusion criterion [2] applies to females of child-bearing potential (not surgically sterilized and between menarche and 1 year postmenopause) only. Test negative for pregnancy at the time of enrollment based on a urine pregnancy test and agree to use a reliable method of birth control (for example, use of oral contraceptives or Norplant; a reliable barrier method of birth control [diaphragms with contraceptive jelly; cervical caps with contraceptive jelly; condoms with contraceptive foam; intrauterine devices]; partner with vasectomy; or abstinence) during the study and for 1 month following the last dose of study drug. [3] Have an AES-C total score >30 at Visit 1 and Visit 2. [4] Have a MADRS total score <15 and Item 1 (apparent sadness) score of <2 at Visit 1 and Visit 2. [5] Have a level of understanding sufficient to provide informed consent and to communicate with the investigators, study coordinator, and site personnel. [6] Are judged by the investigator to be reliable and agree to keep all appointments for clinic visits, tests, and procedures required by the protocol. |
|
| E.4 | Principal exclusion criteria |
| [7] Are investigator site personnel directly affiliated with this study and/or their immediate families. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted. [8] Are Lilly/Boehringer Ingelheim employees. [9] Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an off-label use of an investigational drug or device (other than the study drug used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. [10] Have previously completed or withdrawn from this study or any other study investigating duloxetine. [11] Have had previous lack of response to an adequate trial of duloxetine within the past 12 months. Adequate trial is defined as a minimum dose of duloxetine 60 mg QD for at least 2 months OR any dose of duloxetine for at least 4 weeks. [12] Have had previous lack of response, at any time, to an adequate trial of escitalopram (defined as treatment with at least 10 mg/day of escitalopram for a minimum of 4 weeks). [13] Any current or historical DSM-IV diagnosis (APA 1994) of mania, bipolar disorder, treatment resistant depression (failure of 2 antidepressant trials of adequate dose and duration), or psychosis; or current suicide risk, as assessed by the MINI and C-SSRS. [14] History of DSM-IV-TR substance abuse or dependence within the 6 months immediately prior to Visit 1, excluding nicotine and caffeine. [15] Presence of an Axis II disorder that, in the judgment of the investigator, would interfere with study compliance. [16] Have had treatment with a monoamine oxidase inhibitor (MAOI) within 14 days prior to randomization or the potential need to use an MAOI during the study or within 5 days of discontinuation of study drug. [17] Have had treatment with amphetamines, dopaminergic medications or modafinil within 14 days prior to Visit 2 or potential need to use such medications during the study or within 14 days of discontinuation of study drug. Page 22 Duloxetine hydrochloride F1J-CR-HMGM Protocol Confidential [18] Have a positive urine drug screen for any substance of abuse or excluded medication. Note: If the patient has a positive drug screen at Visit 1 for an excluded prescribed medication that may not have had an adequate wash-out period, a retest may be performed prior to Visit 2. If the retest is positive for the parent compound, the patient will be excluded. [19] Are pregnant or breast-feeding. [20] Have a serious medical illness, including any cardiovascular, hepatic, renal, respiratory, hematologic, endocrinologic, or neurologic disease, or clinically significant laboratory abnormality that is not stabilized or is anticipated to require hospitalization during the study, in the opinion of the investigator. Clinically significant laboratory abnormalities are those that, in the judgment of the investigator, indicate a serious medical problem. [21] Have uncontrolled narrow-angle glaucoma. [22] Have acute liver injury (such as hepatitis) or severe cirrhosis (Child- Pugh Class C). [23] Abnormal thyroid stimulating hormone (TSH) concentration (i.e., outside the reference range of the performing laboratory). Note: Patients diagnosed with hyperthyroidism or hypothyroidism who have been treated on a stable dose of thyroid supplement for at least the past 3 months prior to Visit 1, have a medically appropriate TSH concentration, and are clinically euthyroid are allowedtiroidismo ma che attualmente sono considerati clinicamente eutiroidei, essendo stati stabilizzati con una terapia tiroidea supplementare per almeno i 3 mesi precedenti la visita 2 e mostrano quindi valori di TSH nei range. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary measure of efficacy will be the change from baseline in AES-C total score. Secondary measures of efficacy include AES-C subscale scores, RSAT total and individual item scores, MGHCPFQ total and invidual items scores, PGI-Improvement, CGI-Severity, and MADRS total and item scores. |
|
| 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) | Yes |
| 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.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| 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 |
|
| 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
|
| Ultima Visita dell`Ultimo Paziente |
|
| 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 | |
| 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 | 3 |
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