| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Major Depressive Disorder (MDD) |
|
| 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), extended-release venlafaxine hydrochloride (75mg -150mg once daily) and placebo, in subjects with major depressive disorder (MDD). |
|
| E.2.2 | Secondary objectives of the trial |
To assess the safety and tolerability of extended-release bupropion hydrochloride (bupropion XL), extended-release venlafaxine hydrochloride (venlafaxine XL) and placebo in subjects with MDD.
To assess the effect of bupropion XL, venlafaxine XL and placebo on functional impairment in subjects with MDD.
To assess the effect of bupropion XL, venlafaxine XL and placebo on quality of life in subjects with MDD.
To assess the effect of bupropion XL, venlafaxine XL and placebo on motivation and energy in subjects with MDD.
To assess subject satisfaction with study medication.
To compare the effects on sexual functioning of bupropion XL, venlafaxine XL and placebo in subjects with MDD.
To assess the effect of bupropion XL, venlafaxine XL and placebo, on anxiety in subjects with MDD. |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
Subject must be an outpatient (male or female) and must be aged between 18 and 64 years (inclusive).
Subjects must have a diagnosis of 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).
* Physician assessment must include face-to-face evaluation of the subject, but may
be aided by subject evaluation conducted by a healthcare professional with a
clinically relevant qualification (e.g., psychiatric nurses or psychologists) and a
minimum of two years documented experience assessing patients with Major
Depressive Disorder.
In the investigator’s opinion, subject 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 must have a CGI Severity of Illness (CGI-S) score of ≥4 at both the
Screening Visit and the Baseline Visit.
Female subjects are eligible for entry into the study if she is of:
a. non child-bearing potential (i.e. physiologically incapable of becoming pregnant)
including any female who is pre-menarchal, post-menopausal or surgically sterile
(via hysterectomy, ovariectomy or bilateral ligation); or,
b. child-bearing potential, has a negative serum pregnancy test at the Screening Visit
and one of the following:
• complete abstinence from intercourse from the Screening Visit throughout the
treatment phase of the study, and for a period of at least 7 days after completion of
the study or early withdrawal from the study, or,
• has a male sexual partner who is surgically sterilized, or,
• use of implants of levonorgesterel, or,
• use of injectable progesterone, or,
• use of oral contraceptive (combined or progesterone only), or,
• use of double-barrier contraception, specifically, a spermicide plus a mechanical
barrier (e.g. male condom, female diaphragm), or,
• use of any intrauterine device (IUD) with published data showing that the highest
expected failure rate is less than 1% per year, or,
• use of any other method of contraception with data documented in the product
labelling as approved by regulatory agencies, or in the absence of approved labelling, in peer reviewed studies, showing that the highest expected failure rate for that method is less than 1% per year.
|
|
| 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’s depressive symptoms are due to the direct physiological effects of a
general medical condition (e.g. hypothyroidism, Parkinson's disease, chronic pain).
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 last 12 months.
Subject, in the investigator's judgement, poses a homicidal or serious suicidal risk,
has made a suicide attempt within 6 months prior to the Screening Visit or has ever
been homicidal.
Subjects 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; those treated with other medications or treatment regimes that lower seizure threshold; those 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 the Screening Visit or
has a history of uncontrolled hypertension or unstable heart disease within the 6
months prior to the Screening Visit.
Subject has a history of a medically significant adverse effect (including allergic
reaction) from either bupropion hydrochloride, venlafaxine hydrochloride, their
excipients or closely related compounds.
Subject is taking any medication with potential for pharmacokinetic interaction with
either bupropion hydrochloride, venlafaxine hydrochloride or closely related
compounds.
Subject has taken any psychotropic drugs within 2 weeks prior to the Baseline Visit
including:
• all antidepressants, including but not limited to monoamine oxidase inhibitors
(MAOIs), tricyclic antidepressants (TCAs), serotonin and noradrenaline reuptake
inhibitors (SNRIs), noradrenaline and dopamine reuptake inhibitors (NDRIs),
selective serotonin reuptake inhibitors (SSRIs) (with the exception of fluoxetine, for
which the time period is 4 weeks prior to the Baseline Visit)
• benzodiazepines, sedatives or hypnotics (except for zolpidem, zopiclone or zaleplon, which may be used sparingly, at the recommended dosage, for night time sedation up to two weeks after randomisation)
• other psychoactive medications (including psychoactive herbal treatments, e.g. St.
John's Wort).
Subject has received electroconvulsive therapy (ECT) or transcranial magnetic
stimulation (TMS) within the 6 months prior to the Screening Visit.
Subject has initiated psychotherapy within 3 months prior to the Screening Visit, or
plans to initiate psychotherapy during the study.
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); myocardial strain, ischaemia or
infarct; atrial arrythmia (must be in normal sinus rhythm); second- or third-degree
AV block; congestive heart failure; cor pulmonale; any cardiac condition that the
investigator feels may predispose the subject to ischaemia or arrythmia.
Subject has systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥95
mmHg at either the Screening Visit or the Baseline Visit.
Female subject who is pregnant, lactating or who is planning to become pregnant
during the course of the study.
|
|
| 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 8 Last Observation Carried Forward (LOCF)
endpoint. |
|
| 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 | Information not present in EudraCT |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| 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) | 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.8.5 | 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 |
|
| 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
| |
| 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 | 6 |
| 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 | 0 |
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