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

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 \<30 mL/min
• •Epilepsy
• •Uncontrolled hypothyroidism
• •Uncontrolled hypertension
• •Acute porphyria
• •Urinary retention, prostatic hypertrophy, narrow angle glaucoma or increased intraocular pressure or any other clinically relevant contraindication stated in the Summary of Product Characteristics (SmPC) for citalopram, tramadol or amitriptyline
• •History of significant cardiac dysrhythmia or history of myocardial infarction within 1 year prior to screening
• •Significant history of alcohol or substance abuse
• •Regular alcohol intake above the recommended United Kingdom (UK) guideline of 4 units per day for males or 3 units per day for females
• •Pregnant or lactating women
• •Known hepatitis B or C or human immunodeficiency virus (HIV) or syphilis seropositivity.
• •A corrected QT interval of \>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.