E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Major Depressive Disorder |
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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 | PT |
E.1.2 | Classification code | 10012378 |
E.1.2 | Term | Depression |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
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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 | 10025453 |
E.1.2 | Term | Major depressive disorder NOS |
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 6 weeks treatment of RO4995819 versus placebo as adjunctive therapy in patients with MDD having inadequate response to ongoing antidepressant treatment based on mean change in Montgomery Asberg Depression Rating Scale (MADRS) scores from baseline to end of treatment. |
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E.2.2 | Secondary objectives of the trial |
1. To investigate the safety and tolerability of RO4995819
2. To evaluate the efficacy of RO4995819 versus placebo, according to other efficacy measures
3. To investigate the PK of RO4995819
4. To investigate exposure-response/safety relationships of RO4995819
5. To investigate dynamic biomarkers of depression and treatment response
6. To investigate the impact of known genetic variants on the safety, PK, PD, and efficacy
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• A primary diagnosis of MDD without psychotic features
• Having inadequate response to current antidepressant treatment
• Having at least 1 but no more than 2 antidepressant treatment trial failures within the index depressive episode
• Index depressive episode started within 1 year
• 18 up to 65 years of age
• BMI between 18.0 to 35.0 kg/m2 inclusive
• Patients with reproductive potential must agree to use specified contraceptive protection
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E.4 | Principal exclusion criteria |
• Previously received RO4995819
• History of non-response to, or current use of a non-pharmacological treatment
• Present DSM-IV-TR axis I diagnosis except anxiety comorbidity
• Past or present psychotic symptoms
• Mood disorder due to medical condition or substance use/abuse/dependence
• Established personality disorder
• Alcohol and/or substance abuse/dependence
• A current (at screening) significant risk for suicidal behavior as judged by the Investigator following a thorough clinical evaluation and supported by information collected on the C-SSRS
• Significant or unstable other medical condition that could interfere with the conduct of the study
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in the 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 |
Weekly assessments from baseline to 6 weeks |
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E.5.2 | Secondary end point(s) |
Endpoints related to other efficacy objectives, safety, tolerability, pharmacokinetics and exposure-response/safety relationships of RO4995819 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Up to weekly assessments from baseline to end of study |
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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 | 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 | 4 |
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 | 15 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
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 |
Austria |
Canada |
Germany |
Russian Federation |
Slovakia |
South Africa |
Ukraine |
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 end of the study will be considered to be the date of the last visit (including the last follow-up visit) 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 | 1 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 24 |
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 | 11 |
E.8.9.2 | In all countries concerned by the trial days | 24 |