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 |
Major Depressive Disorder |
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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 | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10057840 |
E.1.2 | Term | Major depression |
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 |
The primary objective is to demonstrate the antidepressant short-term efficacy of at least one of the two doses of agomelatine compared to placebo after 12 weeks of treatment in children (from 7 to less than 12 years of age) and adolescents (from 12 to less than 18 years of age) suffering from moderate to severe Major Depressive Disorder using Children Depression Rating Scale – Revised (CDRS-R) |
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E.2.2 | Secondary objectives of the trial |
- to assess the short-term and long-term safety of agomelatine (10mg, 25mg)
- to evaluate the long-term efficacy of agomelatine (10mg, 25mg)
- to explore efficacy and safety in children and adolescents separately
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female
2. In-or-out patients, considering that hospitalisation is not required for this study
3. Aged from 7 to less than 12 years of age (ICH E11 children age-sub-set, 2001) or from 12 to less than 18 years of age (ICH E11 adolescent age sub-set, 2001)
4. Living with their parents/ legally authorized representative(s)
5. Informed consent/assent obtained from the parents or legally authorized representative(s)/patient: to be defined according to patient’s age and corresponding regulatory requirements in the concerned countries
6. Primary diagnosis of Major Depressive Disorder, single or recurrent episode, of moderate to severe intensity, as per DSM-IV-TR criteria. The diagnosis of MDD according to DSM-IV-TR criteria will be made using a validated semi-structured interview, the Schedule for Affective Disorders and Schizophrenia for School-age Children, Present and Lifetime version
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E.4 | Principal exclusion criteria |
1. Any non-selection criterion which could have appeared after the selection visit
2. Any clinically significant abnormality detected during physical examination, ECG, laboratory test and likely to interfere with the study conduct or evaluation
3. Transaminases values (AST and/or ALT) > 2 times the upper limit of normal range (ULN), total bilirubin > 1.5 times ULN, transaminases (AST and/or ALT) and total bilirubin values > upper reference value, alkaline Phosphates (ALP) > 3 times ULN
4. All types of Depression other than Major Depressive Episode
5. Current suicide risk according to the clinical opinion of the investigator and based on the information obtained during the evaluation of the C-SSRS-C
Hepatic impairment
7. Creatinine Clearance < or = 30 ml/min
8. Abnormal Thyroid Function. |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
All visits except end visit. |
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E.5.2 | Secondary end point(s) |
- Clinical Global Impression: Severity of Illness (CGI-S) and Global Improvement (CGI-I) scores
- Clinical Global Assessment Scale (CGAS) total score
- Adolescent Depression Rating Scale (ADRS) total score (only for adolescents)
- The safety endpoints:
*Adverse events (AE), Pediatric Adverse Event Rating Scale (PAERS)
*Clinical laboratory evaluation (biochemistry, haematology, hormonal parameters)
*Vital signs and clinical examination
*Electrocardiogram
*Columbia Suicidide Severity Rating Scale (C-SSRS-C)
*Tanner stage
*Continuous Performance Task (CPT).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- CGI: All visits except end visit.
- CGAS and ADRS: Inclusion visit, week 4, week 8 and week 12.
- Adverse events (AE): All visits, Pediatric Adverse Event Rating Scale (PAERS): from week 001 and all after visits
- Clinical laboratory evaluation (biochemistry, haematology, hormonal parameters, evaluation of LFT): selection visit, week 002, 008, 012, 018, 024 052, 077 and 104
- Vital signs and clinical examination: selection visit, week 002, 008, 012, 018, 024, 052, 077 and 106
- Electrocardiogram: selection visit, week 012 and 104
- Columbia Suicidide Severity Rating Scale (C-SSRS-C): from inclusion visit and all after visit except end visit
- Tanner stage: inclusion visit, week 012, 052 and 104
- Continuous Performance Task (CPT): inclusion visit, week 012, 052 and 104 |
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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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
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.8.2.4 | 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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 42 |
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 |
Bulgaria |
Finland |
Germany |
Hungary |
Poland |
Romania |
Russian Federation |
South Africa |
Ukraine |
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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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Last visit of last patient. |
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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 | 5 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial months | 6 |