Safety and Efficacy Study Comparing ETS6103 With Amitriptyline in the Treatment of Major Depressive Disorder (MDD)
Condition: Major Depressive Disorder
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Intervention: ETS6103 (low dose); ETS6103 (high dose); Amitriptyline
Intervention MeSH terms: Amitriptyline
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 164.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

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.