Tests Samyr injection added to antidepressant tablets in adults with depression

Who can take part

• Written and signed informed consent needs to be provided by participant before starting any protocol-specific procedures
• Male and female participant between the ages of 18 to 65 years, both ages inclusive
• Participant who is able and willing to comply with the requirements of the study protocol including the visits scheme, assessments and scales
• Primary diagnosis of MDD of at least 12 weeks duration, according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), criteria
• Participant is on prescribed SSRI (citalopram / escitalopram / sertraline / paroxetine) or SNRI (venlafaxine / duloxetine) antidepressant treatment, at approved and stable dose (based on local SmPC), for at least 4 weeks prior to screening
• Partial-response to the prescribed antidepressant during the last 8 weeks prior to screening. Partial response is defined as less than 50% symptom reduction based on the investigator judgment and the treatment history
• Participant who have a Montgomery-Asberg Depression Rating Scale (MADRS) score as assessed by the site investigator of at least 22 at screening and with less than 15% reduction at baseline, post run in treatment. Additionally, participant must have a MADRS score of ≥19 at randomization

Who cannot take part

• Receipt of another investigational drug within 45 days prior to screening, or if the screening visit is within 5 half-lives of another investigational drug received (whichever is longer), or scheduled to receive another investigational drug during the current study period
• Any elective surgery requiring hospitalization planned during the study period
• Use of more than 4 acceptable antidepressant treatments since the diagnosis of depression or treatment with ECT or ketamine during the current episode or lifetime treatment with Vagus Nerve Stimulation (VNS) during the last 5 years
• Previous treatment with Samyr which was not effective or resulted in an AE, or already treatment with Samyr during the current episode
• Treatment with Monoamine Oxidase (MAO)-inhibitors including selegiline and moclobemide, during the 4 weeks prior to screening
• Treatment with linezolid or pimozide
• Treatment with at least one prohibited medication as detailed in appendix 1 (prohibit drug medication prior and during the study)
• History or presence of a medical condition or disease that in the Investigator’s opinion would place the participant at an unacceptable risk as a result of trial participation
• History of bipolar disorders, Schizophrenia and other psychotic disorders
• Hypersensitivity to the active substance or to any of the excipients of Samyr
• Cardiac disorder which in the Investigator’s opinion would place the participant at an unacceptable risk from trial participation
• Any clinically significant abnormality in electrocardiogram (ECG) or safety laboratory tests that in the Investigator’s opinion would place the participant at an unacceptable risk as a result of trial participation
• Known QT interval prolongation or congenital long QT syndrome
• Treatment with products that are known to prolong the QT interval
• Hepatic values that in the Investigator’s opinion would place the participant at an unacceptable risk as a result of trial participation
• Decrease in the baseline MADRS score by ≥ 15% vs screening visit
• Female participant who are pregnant or plan to be pregnant or breast-feeding
• Female participant of childbearing potential who are not able/willing to use oral contraception or acceptable methods of contraception as outlined in this protocol (Protocol Section 4.3), from the time of screening and for the duration of the study, through study completion
• Substance abuse or dependence
• The participant is, in the investigator’s opinion, at significant current risk of harming himself/herself, or provides the following answers on the C-SSRS at screening: - “Yes” to Question 4 or 5 on the Lifetime version Suicidal Ideation section and the ideation was within the last 3 months at Screening Visit, OR - “Yes” to question on the Lifetime version Suicidal Behavior section (other than preparatory behavior) and the ideation was within the last 3 months at Screening Visit, OR - “Yes” to Questions 4 or 5 on the Since Last Visit version of the Suicidal Ideation section at the Baseline Visit - “Yes” to any question on the Suicidal Behavior section at the Baseline Visit
• Participant with known genetic defects which affect the methionine cycle and/or cause homocystinuria and/or hyperhomocysteinaemia (e.g. cystathionine beta-synthase deficiency, defects of vitamin B12 metabolism)