E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
-Cognitive dysfunction
-Major Depressive Disorder (MDD) |
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E.1.1.1 | Medical condition in easily understood language |
-Cognitive dysfunction
-Depression |
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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 | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10057668 |
E.1.2 | Term | Cognitive disorder |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
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 acute treatment with 10 mg/day and 20 mg/day Lu AA21004 versus placebo on cognitive dysfunction. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are to evaluate:
− the efficacy of 10 mg/day and 20 mg/day Lu AA21004 versus placebo on:
- depressive symptoms
- global clinical status
− the proportion of the treatment effect on cognitive dysfunction that is not mediated through an improvement in depressive symptoms.
− the safety and tolerability of 10 mg/day and 20 mg/day Lu AA21004
− the pharmacoeconomics of 10 mg/day and 20 mg/day Lu AA21004
Exploratory objectives are descriebed in the protocol. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• The patient is an inpatient in a psychiatric hospital or an outpatient at a psychiatric setting at the time of the study entry.
• The patient is diagnosed with recurrent MDD according to DSM-IV-TR™ criteria (classification code 296.3x). The current MDE should be confirmed using the Mini International Neuropsychiatric Interview (MINI).
• The patient has received prescribed treatment for a previous episode of depression.
• The patient has a MADRS total score ≥26.
• The reported duration of the current MDE is at least 3 months.
Other protocol-defined inclusion criteria apply.
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E.4 | Principal exclusion criteria |
• The patient has a score ≥70 on the DSST (numbers correct), ≥42 on the RAVLT (learning) and ≥14 on the RAVLT (memory) at the Baseline Visit.
• The patient has any current Axis I disorder (DSM-IV-TR™ criteria) other than MDD, confirmed using the MINI.
• The patient has a current diagnosis or history of manic or hypomanic episode, schizophrenia or any other psychotic disorder, including major depression with psychotic features.
• The patient suffers from personality disorders, mental retardation, pervasive development disorder, attention-deficit/hyperactivity disorder, organic mental disorders, or mental disorders due to a general medical condition (DSM-IV-TR™ criteria).
• The patient has physical, cognitive, or language impairment of such severity as to adversely affect the validity of the data derived from the neuropsychological tests.
• The patient is diagnosed with reading disability (dyslexia).
• The patient is at significant risk of suicide or has a score ≥5 on Item 10 (suicidal thoughts) of the MADRS, or has attempted suicide <6 months prior to the Screening Visit.
• The patient has received electroconvulsive therapy <6 months prior to the Screening Visit.
• The current depressive symptoms are considered by the investigator to have been resistant to 2 adequate antidepressant treatments of at least 6 weeks duration each at the recommended dose.
• The patient has a history of moderate or severe head trauma (for example, loss of consciousness for more than 1 hour) or other neurological disorders or systemic medical diseases that are, in the opinion of the investigator, likely to affect central nervous system functioning.
• The patient has a history of cancer, other than basal cell or Stage 1 squamous cell carcinoma of the skin, that has not been in remission for >5 years prior to the first drug dose.
• The patient has a clinically significant unstable illness (Examples in protocol).
• The patient has, at the Screening Visit, an abnormal ECG that is, in the investigator's opinion, clinically significant.
• The patient is, in the investigator's opinion, unlikely to comply with the protocol or is unsuitable for any reason.
• The patient has previously been exposed to Lu AA21004.
Other protocol-defined exclusion criteria apply.
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E.5 End points |
E.5.1 | Primary end point(s) |
Composite z-score at Week 8 defined as the weighted sum of the standardised change from baseline DSST and RAVLT scores. |
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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) |
Change from baseline to Week 8 using the DSST, number of correct symbols
Change from baseline to Week 8 using the RAVLT, acquisition
Change from baseline to Week 8 using the RAVLT, delayed recall |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
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 | 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 | 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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 37 |
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 |
Australia |
Brazil |
Canada |
Finland |
France |
Germany |
Latvia |
Mexico |
Netherlands |
Serbia |
Slovakia |
South Africa |
Sweden |
Ukraine |
United States |
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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
|
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 | 2 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |