safety and efficacy study comparing ets6103 with amitriptyline in the treatment of major depressive disorder (mdd)

Conditions: Major Depressive Disorder

Summary: to demonstrate that the antidepressant activity of ets6103 is not inferior to amitriptyline in subjects who have an unsatisfactory response to / are resistant to treatment with ssris.


Eligibility criteria:
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 \<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.