E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Major depressive disorder (MDD), Seasonal affective disorder (subtype of MDD) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012378 |
E.1.2 | Term | Depression |
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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 |
Rhythmic 24hour mRNA expression of CLOCK genes, differences in transcript levels of CLOCK genes, differences in the genome-wide gene expression, assessed in mRNA from peripheral blood leucocytes.
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E.2.2 | Secondary objectives of the trial |
Patients with MDD will be post hoc stratified, based on the DSM-IV seasonal pattern specifier (gene expression profiles before and after agomelatine treatment will be compared between MDD and SAD)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
All subjects: • Female or male • Caucasian • Age 18-65 years • Blood pressure <160/100 (measured after 5 minutes in supine position) • Healthy defined as absence of relevant disease or laboratory findings as defined by the investigator • Signed informed consent • Ability to comprehend the full nature and purpose of the study • Negative pregnancy test at screening in women with childbearing potential • No jet lag, shift work, sleep disorders according to ICD 10 or other events interfering with the chronobiological routine within 2 weeks preceding the first study day. • No participation in drug trials within 1 month before the first study day. • No high risk of suicide or a previous suicide attempt within 6 months before the first study day (score >2 on HDRS item 3).
Study group 1 (healthy volunteers) • No intake of psychotropic drugs within the preceding month • Global seasonality score (GSS) lower than 6 • No personal or family history (parents and siblings) of affective disorders or relevant diseases, as defined by the investigator (according to MINI (Sheehan et al., 1998)
Study group 2 (Patients with MDD including SAD) • Fulfilled criteria for a moderate or severe episode of recurrent major depressive disorder (296.32, 296.33) assessed with Structured Clinical Interview for the DSM-IV (SCID) (First et al., 1996). Furthermore patients with SAD must fulfill the criteria for the seasonal pattern specifier according to the DSM-IV-TR • Healthy defined as absence of relevant laboratory findings or disease other than MDD (including SAD) as defined by the investigator. • total Hamilton Depression Rating score (HDRS) of >12 Structured Interview Guide for the Hamilton Depression Rating Scale, (HDRS, 21 items, Hamilton, 1960) • No axis-I co morbidity (according to MINI) (Sheehan et al., 1998) • No intake of psychotropic drugs during the following timeframes before the first study day: - 1 week for most antidepressants (including herbal medication), zolpidem and zopiclone, systemic corticosteroids, ACTH, central alpha-adrenergic agonists, reserpine, methyldopa, exogenous melatonin, and opioides; - 2 weeks for nonselective MAO inhibitors, benzodiazepines, and buspirone; - 3 weeks for fluoxetine (if the duration of treatment had been longer than 7 days); - 4 weeks for lithium, antiepileptics, barbiturates, and antipsychotics; - 6 months for long-acting depot neuroleptics. |
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E.4 | Principal exclusion criteria |
2.5.3 Exclusion criteria • History of relevant diseases as defined by the investogator • Known affective disorder (healthy subjects only) • HIV or Hepatitis B/C positive virology • Any drug intake 1 week prior to the first study day (excluding hormonal contraceptives) • No stable intake of concomitant medication (other than psychotropic drugs) during 4 weeks prior to study day 1. • Presence of relevant illness within the last 3 weeks • Suspected non-compliance with study instructions and life-style requirements • Alcohol or drug abuse • Blood/Plasma donation within 4 weeks prior to the study day • Healthy subjects with a subsyndromal SAD or a “out of range” result in the Neuropsychological test • High risk of suicide or a previous suicide attempt within 6 months before the first study day (score >2 on HDRS item 3). • Pregnant or lactating women
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E.5 End points |
E.5.1 | Primary end point(s) |
Differences in leucocyte gene expression between healthy subjects and patients before and after agomelatine treatment over 14 days including: • Rhythmic 24hour mRNA expression of CLOCK genes • Differences in transcript levels of specific CLOCK genes • Differences in the genome-wide gene expression
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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 | No |
E.6.5 | Efficacy | No |
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 | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
drug given to healthy volunteers |
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E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
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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defined as 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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |