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

Phase 2

Completed

Conditions: Major Depressive Disorder

Interventions: Drug: ETS6103 (high dose)
Drug: ETS6103 (low dose)
Drug: Amitriptyline

Registration Number: NCT02014363

Lead Sponsor: e-Therapeutics PLC

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 164

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ETS6103 (high dose)	ETS6103 (high dose)	ETS6103 (high dose) extended release tablets (encapsulated) taken once daily orally for the duration of randomised phase of the study (8 weeks).
ETS6103 (low dose)	ETS6103 (low dose)	ETS6103 (low dose) extended release tablets (encapsulated) taken once daily orally for the duration of randomised phase of the study (8 weeks).
Amitriptyline	Amitriptyline	Amitriptyline tablets (encapsulated) Standard dosing regime

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Baseline-adjusted (Montgomery-Asberg Depression Scale) MADRS Score at the End of Treatment.	Baseline (start of randomized treatment) and 8 weeks post start of treatment	The mean difference in baseline-adjusted MADRS score at the end of treatment in the per protocol population using the last observation carried forward (LOCF) method. MADRS is used to assess the range of symptoms that are most frequently observed in patients with major depression. The MADRS test includes 10 items and uses a 0 to 6 severity scale, with higher scores indicating increasing depressive symptoms. The total MADRS score is derived by adding all the scores from the 10 items, meaning the lowest possible score is 0 and the highest possible is 60.

Secondary Outcome Measures