| 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 | 12.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10025453 |
| E.1.2 | Term | Major depressive disorder NOS |
|
| 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 | 10025454 |
| E.1.2 | Term | Major depressive disorder, recurrent episode |
|
| 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 two fixed doses of Lu AA21004 (15 or 20 mg/day) versus placebo as assessed by the change from baseline in MADRS total score after 8 weeks of treatment in adult patients with moderate to severe MDD. |
|
| E.2.2 | Secondary objectives of the trial |
Key secondary objectives to compare the effect of Lu AA21004 to that of placebo at Week 8 on:
− patients who respond (response defined as a ≥50% decrease in the MADRS total score from baseline)
− global improvement as assessed by CGI-I
− depressive symptoms in patients with a high baseline level of anxiety (defined by HAM-A), as assessed by MADRS total score
− patients who are in remission (remission defined as a MADRS total score ≤10)
− disability as assessed by SDS total score
Safety objectives to evaluate the:
− effect of Lu AA21004 on sexual function as assessed by ASEX versus placebo
− safety and tolerability of Lu AA21004 (15 or 20 mg/day) versus placebo during treatment
− potential discontinuation symptoms after abrupt discontinuation of treatment with Lu AA21004
Additional objectives are described in the protocol. |
|
| 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 Informed Consent Form. No study-related procedures may be performed before the patient has signed the form.
3. The patient has recurrent Major Depressive Disorder (MDD) as the primary diagnosis according to DSM-IV-TR™ criteria (classification code 296.3x). The current Major Depressive Episode (MDE) should be confirmed using the Mini International Neuropsychiatric Interview (MINI).
4. The patient has a MADRS total score >26.
5. The patient has a CGI-S score >4.
6. The reported duration of the current MDE is >3 months.
7. The patient is a man or woman, aged >18 and <75 years.
8. 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 [that is, <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 Screening Visit, OR
− have been surgically sterilised prior to the Screening Visit, OR
− have had a hysterectomy prior to the Screening Visit.
9. The patient is willing and able to attend study appointments within the specified time windows. |
|
| E.4 | Principal exclusion criteria |
The patient:
1. has previously participated in this study.
2. is a member of the site personnel or their immediate families.
3. is pregnant or breast-feeding.
4. has a history of severe drug allergy or hypersensitivity, or knownhypersensitivity to duloxetine.
5. 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.
6. has a history of lack of response to previous adequate treatment with duloxetine (including current episode).
7. has hereditary problems of fructose intolerance, glucose-galactose malabsorption, or sucrose-isomaltase insufficiency.
8. has any current anxiety psychiatric disorder (DSM-IV-TR™ criteria), as assessed using the Mini International Neuropsychiatric Interview (MINI).
9. has a current diagnosis or 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 (DSM-IV-TR™ criteria).
10. has a current diagnosis or history of alcohol or other substance abuse or dependence (excluding nicotine or caffeine) (DSM-IV-TR™ criteria).
11. has any other disorder for which the treatment takes priority over treatment of MDD or is likely to interfere with study treatment or impair treatment compliance.
12. has a history of moderate or severe head trauma or other neurological disorders or systemic medical diseases that are likely to affect central nervous system functioning.
13. 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 at least 5 years prior to the first dose of IMP.
14. has a clinically significant unstable illness, for example:
− neurological/neurodegenerative disorder
− cardiovascular disease
− seizure disorder or encephalopathy
− congestive heart failure
− cardiac hypertrophy
− arrhythmia
− bradycardia (pulse <50 bpm)
− respiratory disease
− hepatic impairment or renal insufficiency
− metabolic disorder
− endocrinological disorder
− gastrointestinal disorder
− haematological disorder
− infectious disorder
− any clinically significant immunological condition
− dermatological disorder
− venereal disease
15. has a chronic liver disease.
16. takes or has taken 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.
17. has been treated with any investigational medicinal product within 30 days or 5 half lives (whichever is longer) prior to the Screening Visit.
18. has elevated intra-ocular pressure or is at risk of acute narrow-angle glaucoma.
19. has clinically significant abnormal vital signs at the Screening Visit.
20. has one or more laboratory values outside the reference range, based on the blood or urine samples taken at the Screening Visit, 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 Screening Visit:
− 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
− a plasma prothrombin time (expressed as the international normalised ratio [INR]) >1.5 times the upper limit of the reference range
21. has, at the Screening Visit:
− 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/RR0.33)
22. 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 theconduct or interpretation of the study.
23. is, in the investigator’s opinion, unlikely to comply with the protocol or is unsuitable for any reason.
24. is at significant risk of suicide or has a score ≥5 on Item 10 (suicidalthoughts) of the MADRS, or has attempted suicide within 6 months prior to theScreening Visit.
25. is currently receiving formal cognitive or behavioural therapy or systematic psychotherapy, or planning to initiate such therapy during the study.
26. has received electroconvulsive therapy, vagal nerve stimulation, or repetitive trans-cranial magnetic stimulation within 6 months prior to the Screening Visit.
27. has a value of thyroid stimulating hormone (TSH) outside the normal range at the Screening Visit and deemed clinically significant by the investigator.
28. has previously been exposed to Lu AA21004.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint is the change from baseline in MADRS total score after 8 weeks of treatment. |
|
| 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 | Yes |
| 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.8.3 |
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 | 8 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 59 |
| 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
|
| The end of the study for an individual patient is defined as the last protocol-specified contact with that patient. The overall end of the study is defined as the last protocol-specified contact with the last patient ongoing in the study. |
|
| 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 | 1 |
| 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 | 1 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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