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 |
To evaluate the antidepressant efficacy, of extended-release bupropion hydrochloride (150mg-300mg, once daily) compared with placebo, in elderly subjects (aged ≥ 65 years of age) with MDD |
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E.2.2 | Secondary objectives of the trial |
To assess the safety and tolerability of extended-release bupropion hydrochloride compared with placebo in elderly subjects with MDD.
To assess the effect of extended-release bupropion hydrochloride compared with placebo on functional impairment in elderly subjects with MDD.
To assess the effect of extended-release bupropion hydrochloride compared with placebo on quality of life in elderly subjects with MDD.
To assess the effect of extended-release bupropion hydrochloride compared with placebo on motivation and energy in elderly subjects with MDD.
To assess subject satisfaction with study medication.
To assess the effect of extended-release bupropion hydrochloride compared with placebo on anxiety in elderly subjects with MDD. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Subjects must have the ability to comprehend the key components of the consent form and must provide written informed consent prior to commencing any study specific assessments and procedures.
Male or female out-patients aged ≥ 65 years at the time of consent.
Subjects with Major Depressive Disorder, single episode or recurrent, DSM-IV (296.2/296.3) diagnosed with comprehensive psychiatric evaluation as assessed by a physician with adequate training in psychiatry (e.g., Board Certification in US; Certificate of Completion of Specialist Training in EU).
In the investigator’s opinion, subjects must have met DSM-IV criteria for their current major depressive episode for at least 8 weeks.
Subject must have an IVRS HAMD-17 total score of ≥ 18 at both the Screening Visit and the Baseline Visit, as assessed via an Interactive Voice Response (IVR) rating system.
Subject has a CGI Severity of Illness (CGI-S) score of ≥ 4 at the Screening Visit and Baseline Visit.
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E.4 | Principal exclusion criteria |
Subject’s IVRS HAMD-17 total score increases or decreases by more than 25% between the Screening and Baseline visits.
Subject has a history of manic episodes.
Subject has a past or current DSM-IV diagnosis of Schizophrenia, or any other psychotic disorder(s).
Subject has a current DSM-IV Axis II diagnosis that would suggest nonresponsiveness to pharmacotherapy or non-compliance with the protocol (e.g. antisocial or borderline personality disorders).
Subject has a diagnosis of anorexia nervosa or bulimia within the past 12 months.
Subject is diagnosed with dementia.
Subject has a score of ≤ 24 on the Mini Mental State Exam (MMSE) at the Screening Visit.
Subject, in the investigator’s judgement, poses a homicidal or serious suicidal risk, has made a suicide attempt within the six months prior to the Screening Visit or has ever been homicidal.
Subject has current or past history of seizure disorder or brain injury (traumatic or disease-related), or any condition which, in the opinion of the investigator, predisposes to seizure; subject treated with other medications or treatment regimens that lower seizure threshold; subject undergoing abrupt discontinuation of alcohol or sedatives (including benzodiazepines or benzodiazepine-like agents). Note: single childhood febrile seizure is not exclusionary.
Subject has had a myocardial infarction within 1 year prior to Screening Visit or as a history of uncontrolled hypertension, or unstable heart disease within the 6 months prior to the Screening Visit.
Subject has a history of medically significant adverse effect (including allergic reaction) from bupropion hydrochloride, it’s excipients, or closely related compounds.
Subject is taking any medication with potential for pharmacokinetic interaction with bupropion hydrochloride or closely related compounds. These medications should not be taken during the Screening, Treatment, or Follow-up phases of the study.
Subject has taken any psychotropic drugs within two weeks prior to the Baseline Visit.
Subject has taken bupropion hydrochloride in the last 6 months.
Subject has initiated psychotherapy within 3 months prior to the Screening Visit, or plans to initiate psychotherapy during the study.
Subject has received electro-convulsive therapy (ECT) or trans-cranial magnetic stimulation (TMS) within 6 months prior to the Screening Visit.
Subject has previously failed adequate courses (e.g. maximum-labelled doses for ≥ 4 weeks) of pharmacotherapy with two different classes of antidepressants.
Subject has a positive urine test at screening for illicit drug use and/or a history of alcohol or substance abuse or dependence within the past 12 months or subject has a blood alcohol level of >15 mg/dl (0.015%) at the Screening Visit.
Subject has ECG or clinical evidence of atrial or ventricular hypertrophy; intraventricular conduction defects (excluding incomplete right bundle branch block in the absence of clinical evidence of heart disease); symptomatic coronary artery disease (or any symptomatic cardiac disease); myocardial strain, ischaemia, or infarct; atrial arrhythmia (must be in normal sinus rhythm); second- or third-degree AV block; congestive heart failure; cor pulmonale; or any cardiac condition that the investigator feels may predispose the subject to ischaemia or arrhythmia.
Subject has systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 95 mmHg at either the Screening Visit or Baseline Visit. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) total score at Week 10 Last Observation Carried Forward (LOCF) endpoint. |
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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) | 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.8.5 | 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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
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 | 3 |