E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Major Depressive Disorder (MDD) |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025463 |
E.1.2 | Term | Major depressive disorder, single episode |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
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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 evaluate the efficacy of two fixed doses of RO4917523 compared to placebo over 6 weeks as adjunctive therapy in patients with MDD with inadequate response to ongoing antidepressant treatment. The change will be measured based on the mean change in the Montgomery Asberg Depression Rating Scale (MADRS) total score from baseline to end of treatment. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to evaluate change after 6 weeks of treatment with RO4917523 as add-on therapy versus placebo in the following:
• Global Impression Scores: Clinical Global Impression of Severity (CGI-S) from baseline to end of treatment, Clinical Global Impression of Improvement (CGI-I) at end of treatment, and Patient Global Impression of Improvement (PGI-I) at end of treatment
• Safety and tolerability of RO4917523
• Proportion of patients exhibiting remission and response (based on a priori definitions related to change in the MADRS score)
• Quick Inventory of Depressive Symptomatology Self Report score (QIDS-SR16)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Primary diagnosis of Major Depressive Disorder (MDD) without psychotic features as defined by DSM-IV-TR criteria, and determined on the basis of the MINI structured interview.
• Having inadequate response to an ongoing antidepressant treatment:
• Inadequate response, defined as a CGI-S score of at least moderately ill and a priory determined level of severity in MADRS score.
• Antidepressant treatment defined as pharmacotherapy with a selective serotonin reuptake inhibitor (SSRI) or serotonin and norepinephrine reuptake inhibitor (SNRI) of at least 6 weeks duration at the minimum acceptable dose.
• Dose and duration of ongoing antidepressant treatment must be verified during the screening period
• Having at least one but no more than three antidepressant treatment failures within the current depressive episode.
• Age 18 -70
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E.4 | Principal exclusion criteria |
• Currently receiving treatment with a combination of antidepressants (two or more), or on adjunctive or potentiating treatment.
• Previously received RO4917523
• Past or current use (defined a priory) of Electroconvulsive Therapy, Repetitive Transcranial Magnetic Stimulation, Vagus Nerve Stimulation, or Deep Brain Stimulation may be exclusionary
• Other current DSM-IV-TR axis I diagnosis. Comorbid anxiety which dominates the clinical presentation or troubles the patient the most is not accepted: Obszessive-Compulsive Disorder (OCD) and Posttraumatic Stress Disorder (PTSD) are specifically not allowed under an circumstances.
• Current or past history of psychotic symptoms or of Bipolar Disorder
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in the Montgomery Asberg Depression Rating Scale (MADRS) total score from baseline to end of treatment. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From baseline to end of treatment (6 weeks) |
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E.5.2 | Secondary end point(s) |
• Change in Clinical Global Scores Severity (CGI-S) from baseline to end of treatment and Improvement (CGI-I) at end of treatment
• Patient Global Impression of Improvement (PGI-I) score at end of treatment
• Frequency of patients exhibiting remission or response (based on a priori definition related to change in MADRS score) at end of treatment
• Quick Inventory of Depressive Symptomatology Self Report (QIDS-SR16) change from baseline to end of treatment
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
From baseline to end of treatment (6 weeks) |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 10 |
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 | No |
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 |
Chile |
Germany |
India |
Japan |
Mexico |
Poland |
Romania |
Russian Federation |
Taiwan |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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The date of the last visit (including the follow-up period) of the last patient in the study |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 21 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 21 |