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

Major Depressive Disorder Clinical Trial

— ETS6103-003  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02014363
• Other study ID #: ETS6103-003
• Secondary ID: 2013-000719-26
• Status: Completed
• Phase: Phase 2
• First received: December 12, 2013
• Last updated: April 26, 2016
• Start date: October 2013
• Est. completion date: October 2015

Study information

• Verified date: April 2016
• Source: e-Therapeutics PLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 162
• Est. completion date: October 2015
• Est. primary completion date: October 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

Drug:
• ETS6103 (low dose)

• ETS6103 (high dose)

• Amitriptyline

Locations

Country	Name	City	State
United Kingdom	CPS Research	Glasgow	Scotland

Sponsors (1)

Lead Sponsor	Collaborator
e-Therapeutics PLC

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The mean difference in baseline-adjusted (Montgomery-Asberg Depression Scale) MADRS score at the end of treatment.	The MADRS will be measured at every visit	8 weeks	No
Secondary	Assessment of MADRS score throughout the randomised study period	The mean difference in baseline-adjusted MADRS score at weeks 1, 2, 4 and 6. Percentage of subjects with remission defined as = 10 on the MADRS at the end of treatment.; Percentage of responders defined as = 50% decrease from baseline in the MADRS at the end of treatment (week 8)	Randomised treatment weeks 1, 2, 4, 6 and 8	No
Secondary	Assessment of Clinical Global Impression (CGI) of Severity / Improvement Scale	The mean difference in baseline-adjusted CGI severity at week 8. The mean difference in CGI improvement at weeks 1, 2, 4, 6 and 8.	Randomised treatment weeks 1 to 8	No