Safety and Efficacy Study Comparing ETS6103 With Amitriptyline in the Treatment of Major Depressive Disorder (MDD)

Inclusion Criteria

• Signed informed consent
• Male or female
• Age 18-65 years inclusive
• Subjects with a current episode of moderate to severe Major Depressive Disorder meeting the criteria of Diagnostic and Statistical Manual of Mental Disorders (DSM) IV -TR and documented using the brief structured interview Mini International Neuropsychiatric Interview (MINI) version 5.0 and with a minimum duration of two weeks and a maximum of twelve months
• Minimum Hamilton Depression Scale (HAM-D) 17 items total score of 18 at screening and ≥12 at the end of the lead-in phase prior to randomization.
• Female subjects of childbearing potential must have a negative pregnancy test at the Screening Visit and must use an acceptable method of contraception throughout the study and for 30 days after. Male subjects with female partners of child-bearing potential must use an acceptable method of contraception throughout the study and for 30 days after.
• Able to understand and comply with the requirements of the study as judged by the investigator

Exclusion Criteria

• Considered by the investigator to be at significant risk of suicide or scoring 5 or more on the Montgomery Asberg Depression Rating Scale (c) question 10
• Significant other psychiatric illness which would interfere with trial assessments co-morbid generalized anxiety disorder (GAD) and panic disorder will be permitted where MDD is considered the primary diagnosis
• Significant physical illness which would interfere with trial assessments
• Recent (within 1 week of screening) antidepressants (except for fluoxetine [within 4 weeks of screening] and St John's Wort or Monoamine oxidase inhibitors (MAOI) [within 14 days of screening]),
• Benzodiazepine or any other psychotropic medication including lithium or other mood stabilizers within 1 week of screening
• Oral anticoagulant therapy within one month of screening
• Formal psychotherapy or alternative treatments for one week prior to screening or during the study
• Reduced hepatic function defined as liver enzyme levels ≥2.5 times upper limit of normal
• Renal insufficiency defined as creatinine clearance 470ms for female subjects of >450ms for male subjects, calculated using the QTcB (Bazett Correction Formula) , or second degree or higher heart block on an electrocardiography (ECG) recording, at screening.
• Allergy to the study drugs or excipients
• Treatment with another investigational medicinal product within the 30 days prior to screening.