Clinical trial NCT02014363: Safety and Efficacy Study Comparing ETS6103 With Amitriptyline in the Treatment of Major Depressive Disorder (MDD)
Official title: Double Blind, Non-inferiority Study to Evaluate the Antidepressant Activity of ETS6103 Compared to Amitriptyline in Treating Major Depressive Disorder in Patients With Unsatisfactory Response to Selective Serotonin Re-uptake Inhibitors.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Major Depressive Disorder
Lead sponsor: e-Therapeutics PLC
Sponsor class: INDUSTRY
First posted: 2013-12-18
Enrollment: 164
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Change From Baseline in Baseline-adjusted (Montgomery-Asberg Depression Scale) MADRS Score at the End of Treatment.
timeFrame: Baseline (start of randomized treatment) and 8 weeks post start of treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Glasgow
country: United Kingdom
facility: CPS Research
state: Scotland
Study officials:
affiliation: CPS Research
name: Alan G Wade, MBChb
role: PRINCIPAL_INVESTIGATOR
References: