A Phase 3 Study of Lu AA21004 in Patients With Major Depressive Disorder

This is a randomized, double-blind, placebo-controlled, parallel-group, phase III study to assess the efficacy and safety of 8-week treatment of two fixed doses of Vortioxetine (Lu AA21004; 10 or 20 mg/day) in Japanese participants with major depressive disorder (MDD).

Inclusion criteria

• In the opinion of the investigator or sub-investigator, the participant is capable of understanding and complying with protocol requirements.
• The participant signs and dates a written, informed consent form prior to the initiation of any study procedures.
• The participant suffers from recurrent MDD as the primary diagnosis according to Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) criteria (classification code 296.3x).
• The participant is a man or a woman aged 20 to 75 years (both inclusive) at the time of informed consent.
• The reported duration of the current major depressive episode is 3 to 12 months (both inclusive) at the start of screening period.
• The participant has a MADRS total score ≥26, Hamilton Depression Rating Scale (HAM-D17) total score ≥18, and Clinical global impression scale-Severity (CGI-S) score ≥4 at the start of screening period, at the start of placebo lead-in period and at the start of double-blind treatment period.
• A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent to the end of the follow-up period.

Exclusion criteria

• The participant has any following current or past history of psychiatric disorder and/or neurological disorder:

• Any current psychiatric disorder other than MDD as defined by DSM-IV-TR (To be assessed by Mini International Neuropsychiatric Interview: MINI). A participant who exhibits symptoms of anxiety is eligible unless the participant fulfills the diagnostic criteria for a current anxiety disorder per DSM-IV-TR.
• Current diagnosis or history of manic, mixed or hypomanic episode, MDD with psychotic features, schizophrenia or any other psychotic disorder (including substance-related mental disorders, or mental disorders due to a general medical condition) as defined by DSM-IV-TR.
• Current diagnosis or history of any substance-related disorder (except nicotine and caffeine-related disorders) as defined by DSM-IV-TR.
• The participant with a positive urine drug screening result at the start of screening period or the start of placebo lead-in period. In case that a participant showed positive test result at the start of screening period because the test was conducted before washout of pretreatment drug, the participant is eligible as long as he/she shows negative result at the start of placebo lead-in period.
• Presence or history of any clinically significant neurological disorder (including epilepsy).
• Any neurodegenerative disorder (e.g. Alzheimer's disease, Parkinson's disease, multiple sclerosis, Huntington's disease).
• Any DSM-IV-TR axis II disorder.
• The participant has the current or previous major depressive episode which was considered by the investigator or sub-investigator to have been resistant to 2 or more adequate antidepressants treatments of at least 6 weeks duration each at sufficient doses.
• The participant has received any augmentation therapy (e.g. lithium, T3/T4, lamotrigine, sodium valproate, carbamazepine, additional atypical antipsychotic, or concomitant use of other antidepressant, etc.) for the current major depressive episode.
• In the opinion of the investigator or sub-investigator, the participant has experienced significant number of major depressive episodes in the past, and is suspected of disease other than MDD.
• In the opinion of the investigator or sub-investigator, the participant has experienced the first major depressive episode at his/her young age, and is suspected of disease other than MDD.
• The participant has a MADRS total score at the start of double-blind treatment period that has improved or aggravated by 25% or more from the score at the start of placebo lead-in period.
• The participant is significantly non-compliant with the study drug in the placebo lead-in period; e.g., not taking the study drug for 6 or more consecutive days.
• The participant has received electroconvulsive therapy, vagus nerve stimulation, or repetitive transcranial magnetic stimulation therapy within 6 months prior to the screening period, or plans to initiate such therapy during the study.
• The participant is receiving cognitive-behavioral therapy or psychotherapy at the time of informed consent, or plans to initiate such therapy during the study.
• The participant is at significant risk of suicide or has a score ≥5 on Item 10 (suicidal thoughts) of the MADRS at the start of screening period, at the start of placebo lead-in period or at the start of double-blind treatment period, or has attempted suicide within 6 months prior to the start of screening period.
• The participant has experienced any environmental change (e.g. temporary retirement, returnment, change of residence) considered by the investigator or sub-investigator to have the potential to impact on the efficacy evaluation, or plans such environmental changes during the study.
• The participant is currently receiving drug therapy for thyroid dysfunction.
• The participant is currently receiving hormonal therapy for gynecological disease.
• The participant has taken excluded medications during the protocol-specified period, or will require to take excluded medications during the study.
• The participant has previously received vortioxetine.
• The participant has received study drug in a previous clinical study of Lu AA21004 (including this study).
• The participant has a clinically significant chronic liver disease.
• The participant has a history of severe allergy or hypersensitivity to drugs.
• The participant has a clinically significant unstable illness, for example, liver disorder or renal insufficiency, or a cardiovascular, pulmonary, gastrointestinal, endocrine, neurological, rheumatologic, immunologic, infectious, neoplastic, skin and subcutaneous tissue disorders, eye disorders, or metabolic disturbance.
• The participant has clinically significant abnormal vital signs as determined by the investigator or sub-investigator at the start of screening period, placebo lead-in period, or double-blind treatment period.
• The participant has clinically significant abnormal electrocardiogram (ECG) as determined by the investigator or sub-investigator, at the start of the screening period, at the start of placebo lead-in period, or at the start of double-blind treatment period.
• The participant has clinically significant abnormal findings of clinical laboratory tests as determined by the investigator or sub-investigator, or has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 × ULN at the start of screening period or at the start of placebo lead-in period.
• If female, the participant is pregnant or lactating.
• The participant has a disease or takes medications that could, in the opinion of the investigator or sub-investigator, interfere with the evaluation of the safety, tolerability, or efficacy.
• The participant is, in the opinion of the investigator or sub-investigator, unsuitable for this study for any other reason.