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 (MDD) is characterised by loss of interest or pleasure, disturbed sleep or appetite, low energy, feelings of guilt or low self-worth, and poor concentration.
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025454 |
E.1.2 | Term | Major depressive disorder, recurrent episode |
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 | 13.1 |
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 long-term safety and tolerability of flexible doses of Lu AA 21004 (15 and 20 mg/day) during 52-weeks treatment period in patients with Major Depressive Disorder (MDD) who have completed Study 13267A. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the therapeutic effect of flexible doses of Lu AA21004 (15 and 20 mg/day) over a period of 52 weeks in patients with MDD as assessed by MADRS, CGI-S and HAM-A
Additional Objectives of the trial are described in the protocol:
To evaluate the effect of Lu AA21004 on:
- health-related quality of life and satisfaction, related to various areas of functioning as assessed by Q-LES-Q (SF)
- health-related quality of life, related to disability as assessed by SDS
- health-related quality of life, related to health care utilization as assessed by HEA
- health-related quality of life as assessed by EQ-5D health questionnaire
- work productivity as assessed by WPAI
- sexual function as assessed by ASEX
- suicidal ideation and behaviour as assessed by C-SSRS
To evaluate the population pharmacokinetics of Lu AA21004.
To explore associations between biological parameters and clinical features such as disease symptoms, drug response and potential adverse events. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. The patient is able to read and understand the Informed Consent Form.
2. The patient has signed the new Informed Consent Form, which is separate from the signed informed consent obtained for the lead-in Study 13267A. No study-related procedures may be performed before the patient has signed the form.
3. The patients has completed the lead-in Study 13267A (Visit 9, end of Week 10) immediately prior to enrolment into this extension study.
4. The patient suffers from Major Depressive Disorder (MDD) according to DSM-IV-TR™ criteria (classification code 296.3x) at the entry into the lead-in Study 13267A.
5. The patient, if a woman, must:
- agree not to try to become pregnant during the study, AND
- use adequate, highly effective contraception, defined as those that result in a low failure rate (less than 1% per
year), when used consistently and correctly, for example, implants, injectables, combined oral contraceptives, some intrauterine devices, sexual abstinence, vasectomised partner), OR
- have had her last natural menstruation at least 24 months prior to the Baseline Visit, OR
- have been surgically sterilised prior to the Baseline Visit, OR
- have had a hysterectomy prior to the Baseline Visit.
6. The patient is willing and able to attend study appointments within the specified time windows.
7. The patient is judged to benefit from 52-week continuation treatment with Lu AA21004 according to the clinical opinion of the investigator. |
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E.4 | Principal exclusion criteria |
1. The patient has previously participated in this study.
2. The patient has been diagnosed with a psychiatric disorder other than MDD (mania, bipolar disorder,schizophrenia or any other) during the lead-in Study 13267A.
3. The patient has a clinically significant unstable illness diagnosed during the lead-in Study 13267A.
4. The patient, in the investigator’s clinical judgment, has a significant risk of suicide and/or a score of ≥5 points on item 10 (suicidal thoughts) of the Montgomery-Åsberg Depression Rating Scale (MADRS).
5. The patient has a moderate or severe ongoing adverse event related to study medication from the lead-in Study 13267A considered of potential safety risk by the investigator.
6. The patient takes or has taken any disallowed recent or concomitant medication, specified in Appendix II - Or it is anticipated that the patient will require treatment with at least one of the disallowed concomitant medications during the study.
7. The patient has a disease or takes medication that could, in the investigator’s opinion, interfere with the assessments of safety, tolerability, or efficacy, or interfere with the conduct or interpretation of the study.
8. The patient has clinically significant abnormal vital signs at the Completion Visit (Visit 7, end of Week 8)of the lead-in Study 13267A considered of potential safety risk by the investigator.
9. The patient has one or more laboratory values outside the reference range, based on the blood or urine samples taken at the Completion Visit (Visit 7, end of Week 8) of the lead-in Study 13267A, that are, in the investigator’s opinion, of potential risk to the patient’s safety, or the patient has any of the following values at the Completion
Visit (Visit 7, end of Week 8) of the lead-in Study 13267A:
- a serum creatinine value >1.5 times the upper limit of the reference range
- a serum total bilirubin value >1.5 times the upper limit of the reference range
- a serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value >2 times the upper limit of the reference range.
10. The patient has, at the Completion Visit (Visit 7, end of Week 8) of the lead-in Study 13267A:
- an abnormal ECG that is, in the investigator’s opinion, clinically significant
- a PR interval >250 ms
- a QRS interval >130 ms
- a QTcF interval >450 ms (for men) or >470 ms (for women) (based on the Fridericia correction where QTcF = QT/RR 0.33).
11. The patient is a member of the site personnel or their immediate families.
12. The patient is pregnant or breast-feeding.
13. The patient has a history of severe drug allergy or hypersensitivity, or known hypersensitivity to LuAA21004.
14. The patient is currently receiving formal cognitive or behavioural therapy or systematic psychotherapy except bereavement counselling, or planning to initiate such therapy during the study.
15. The patient is unlikely to be able to comply with the clinical protocol or is unsuitable for any other reason, in the opinion of the investigator. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the change from baseline in MADRS total score after 52 weeks of treatment. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Therapeutic effect of flexible doses of Lu AA21004 (15 and 20 mg/day) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
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 | No |
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 | No |
E.8.2.3 | Other | No |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 69 |
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 |
Russian Federation |
South Africa |
Ukraine |
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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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The end of the study for an individual patient is defined as the last protocol-specified contact with the patient. The overall end of the study is defined as the last protocol-specified contact with the last patient ongoing 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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |