E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Major Depressive Disorder |
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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 efficacy of a 100 mg fixed dose of saredutant compared to placebo in patients with major depressive disorder |
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E.2.2 | Secondary objectives of the trial |
To evaluate the tolerability and safety of saredutant in patients with major depressive disorder. To evaluate the efficacy of saredutant compared to placebo on disability and quality of life in patients with major depressive disorder. To evaluate plasma concentrations of saredutant and SR49596 and explore their relationships to efficacy and safety outcomes. To evaluate the safety and tolerability of forty-four weeks of additional treatment with saredutant in patients completing the initial eight-week treatment period. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
- Male or female patients. - 18 to 64 years of age. - In patients or out patients. - Written informed consent from the patient and/or legally authorized representative. - Able to comply with the protocol and follow written and verbal instructions. - Subjects of childbearing potential must have a confirmed negative serum beta-hCG prior to entry into Segment B and must employ an acceptable method of birth control at least on month prior to entry into Segment A, throughout the study, and at least one month after study completion. - Diagnostic of major depressive disorder, as defined by DSMIV TR. - Minimum total score of 22 on the MADRS. |
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E.4 | Principal exclusion criteria |
- Patients whose current depressive episode is diagnosed with psychotic features, catatonic features, seasonal pattern or post-partum onset. - The duration of the current depressive episode is greater than 2 years. - Patients having a current score of >5 on the suicidal thoughts item of the MADRS (item 10) and/or a score of 4 on the suicide item (item 3) of the Hamilton Depression Rating Scale at screening (V1, Day –7) or baseline (V2, Day –1) and/or endorses a Yes response (10 points) to items 4 (Have a suicide plan?) or 5 (Attempt suicide) of the C (suicidality) criteria of the MINI. - History of a suicide attempt within 3 years prior to entry into Segment A. - Patients whose current depressive episode is secondary to a general medical disorder (293.83). - Patients with a history or presence or some other concomitant psychiatric disorders according to MINI criteria. - Patients with alcohol dependence or abuse or substance dependence or abuse in the past 12 months according to the MINI, except nicotine or caffeine dependence. - Patients who have used the following prior to entry into Segment B : any antipsychotic within 3 months - fluoxetine within 35 days - any MAOI within 21 days - any other antidepressant, anxiolytic, sedative-hypnotic, or mood-stabilizer (lithium, anticonvulsants) within 7 days except permitted concomitant medications as defined in (Section 9.9.2). - Patients who test positive for any illicit drug included in the urine drug screen Visit 1 (Day - 7). - A 20% or greater decrease in MADRS total score during Segment A or a MADRS total score of<22 at entry into Segment B. - Females who are pregnant or breast-feeding. - Severe or unstable cardiovascular, renal, hepatic, respiratory, hematological, endocrinological, neurological, or other somatic disease that, according to the Investigator's judgment, might interfere with the evaluation of study medication. - ECG abnormalities of potential clinical significance including a QT interval with Bazett's correction (QTcB) > or equal to 500msec at entry into Segment B. - Use of known inducers or potent inhibitors of CYP3A4 within 7 days of entry into Segment B. These medications should be discontinued at entry into Segment A. See (Appendix 1) for a list of CYP3A4 inhibitors and inducers. Note that phenobarbital should be washed out for at least 30 days prior to entry into Segment B. - Use of drugs with known risk for Torsade de Pointes within 7 days of entry into Segment B. All medications listed (Appendix 2) should be discontinued at entry into Segment A and washed out for the full 7 days of Segment A. - Patients not compliant in taking study medication during Segment A (e.g., takes less than 80% of the prescribed number of capsules). - Patients with a positive HbsAg or anti-HCV antibody test at screening (V1, Day –7). - Patients with any of the following at screening (V1, Day –7): ALT >2 times the upper limit of the normal range AST >2 times the upper limit of the normal range GGT >3 times the upper limit of the normal range total or conjugated bilirubin above the upper limit of the normal range
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline to Day 56 in the 17-item Hamilton Depression Rating Scale (HAM-D) total score. |
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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 | 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 | Yes |
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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | Information not present in EudraCT |
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 | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |