E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Major Depressive Disorder |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10057840 |
E.1.2 | Term | Major depression |
|
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 of this study is to prove efficacy of one or more doses of Lu AA24530 relative to placebo. |
|
E.2.2 | Secondary objectives of the trial |
Compare the efficacy of Lu AA24530 to that of pbo in terms of proportion of pts w. response and remission after 6-weeks and 14 days of treatm. that is maintained or further improved at 6-w. Compare the efficacy of Lu AA24530 to that of pbo in terms of change from Baseline on the total MADRS score during the course of the study. Assess the safety and tolerability of Lu AA24530 Analyse exploratorily the population PK of Lu AA24530 and its metabolite Lu AA37208 in depressed pts and to evaluate any relationship between exposure and efficacy, tolerability, and safety Evaluate the efficacy of Lu AA24530 on the subpopulations of pts with MDD with melancholic- and atypical features Evaluate the effect on pain, cognitive deficits and on Health Related QoL of Lu AA24530. Conduct exploratory analyses of biomarkers to better understand the pathophysiology of MDD and the treatment response
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
The patient is able to read and understand the Patient Information Sheet. The patient has signed the Informed Consent Form. The patient has a Major Depressive Episode (MDE), diagnosed according to DSM-IV-TR criteria (classification code 296.xx) and confirmed according to the Mini-International Neuropsychiatric Interview (MINI) . The patient is a man or a woman, aged between 18 and 65 years (extremes included). The patient has a Major Depressive Episode that has lasted at least 3 months. The patient has a MADRS of total score ≥ 26. The patient is able to swallow capsules. The patient, if female, must: agree not to try to become pregnant during the study, AND use adequate contraception (adequate contraception is defined as oral/systemic contraception, intrauterine device, diaphragm in combination with spermicide, or condom for male partner in combination with spermicide), OR have had her last natural menstruation at least 24 months prior to Baseline, OR have been surgically sterilised prior to Baseline, OR have had a hysterectomy prior to Baseline, OR not be sexually active.
|
|
E.4 | Principal exclusion criteria |
The patient has one or more of the following conditions: Any current psychiatric disorder established as the principal diagnosis other than MDD as defined in the DSM-IV-TR and assessed with the Mini-International Neuropsychiatric Interview (MINI), current or past history of: manic or hypomanic episode, schizophrenia or any other psychotic disorder, including major depression with psychotic features, mental retardation, organic mental disorders, or mental disorders due to a general medical condition as defined in the DSM-IV-TR, any substance use disorder (except nicotine) within the previous 6 months as defined in the DSM-IV-TR, presence or history of a clinically significant neurological disorder, any axis II disorder that might compromise the study. The patient is at significant risk of suicide either corroborated by MINI item A3g, a score ≥5 on item 10 (suicidal thoughts) on the MADRS, ≥4 on item 3 of the HAM-D-17 (suicidal thoughts), or according to investigator’s opinion. The patient has a Major Depressive Episode that has been unresponsive to two adequate courses of antidepressant treatment of each at least 6 weeks duration. The patient has a history of lack of response to previous treatment with duloxetine. The patient has a history of severe drug allergy or hypersensitivity, or known hypersensitivity to duloxetine. The patient has received electroconvulsive therapy within 6 months prior to Baseline. The patient used/uses 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. The patient is currently receiving formal cognitive or behavioural therapy, systematic psychotherapy, or plans to initiate such therapy during the study. The patient has a clinically significant unstable illness, for example, hepatic or renal insufficiency, or a cardiovascular, pulmonary, gastrointestinal, endocrine, neurological, infectious, neoplastic, or metabolic disturbance.The patient has increased intra-ocular pressure or is at risk of acute narrow-angleglaucoma.The patient has a chronic liver disease. The patient has abnormal vital signs judged by the investigator to be indicative of significant illness. The patient has a history of seizures. The patient has a history of renal illness or damage or decreased renal function. The patient has one or more laboratory values outside the normal range, based on the blood samples taken at the Screening Visit, that are considered by the investigator to be indicative of significant illness. The patient has a thyroid-stimulating hormone (TSH) out of normal range The patient has an abnormal ECG judged by the investigator to be indicative of significant illness. The patient has a QTc above 450 ms. The patient has a history of hypokalaemia. The patient has a family history of Long QT Syndrome. The patient has a disease or takes medication that, in the opinion of the investigator, could interfere with the assessments of safety, tolerability, or efficacy. The patient has been treated with any investigational medicinal product within 30 days or 5 half lives (whichever is longer) prior to Baseline. The patient has a positive urine drug screen. The patient is pregnant or breast-feeding. The patient, in the opinion of the investigator, is unlikely to comply with the clinical study protocol or is unsuitable for any reason. The patient is a member of the site personnel or their immediate families. The patient has previously participated in this study. The patient has previously been exposed to Lu AA24530 |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of interest is MADRS total score at Week 6. Secondary endpoints are MADRS total score at all time points, MADRS remission and response after 6 weeks and MADRS sustained response after 2 weeks. Also safety and tolerability measured by vital signs, ECGs, laboratory measurements, weight, adverse events and withdrawal rates, are considered as secondary endpoints. In addition HAM-D-17, CGI-I, CGI-S, SF-36, pain assessments, and cognition outcomes will be analysed at all time points (where rated).
|
|
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 | 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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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.8.3 |
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.8.5.1 | 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 | 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 |
|
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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |