Safety and Efficacy Study Comparing ETS6103 With Amitriptyline in the Treatment of Major Depressive Disorder (MDD) (ETS6103-003)

e-Therapeutics

Status and phase: Completed; Phase 2

Conditions: Major Depressive Disorder

Treatments: Drug: ETS6103 (low dose); Drug: ETS6103 (high dose); Drug: Amitriptyline

Study type: Interventional

Funder types: Industry

Identifiers

NCT02014363

ETS6103-003

2013-000719-26 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 164 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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164 participants in 4 patient groups

ETS6103 (low dose)

Experimental group

Description:

ETS6103 (low dose) extended release tablets (encapsulated) taken once daily orally for the duration of randomised phase of the study (8 weeks).

Treatment:

Drug: ETS6103 (low dose)

ETS6103 (high dose)

Experimental group

Description:

ETS6103 (high dose) extended release tablets (encapsulated) taken once daily orally for the duration of randomised phase of the study (8 weeks).

Treatment:

Drug: ETS6103 (high dose)

Amitriptyline

Active Comparator group

Description:

Amitriptyline tablets (encapsulated) Standard dosing regime

Treatment:

Drug: Amitriptyline

Lead-in phase

No Intervention group

Description:

Citalopram tablets: Standard dosing regime