A Study to Assess the Effect and Safety of AZD6765 in Patients With Major Depressive Disorder

A Multicenter, Randomized, Double-blind, Parallel Group, Placebo-controlled, Phase IIb Efficacy and Safety Study of Adjunctive AZD6765 in Patients With Major Depressive Disorder (MDD) and a History of Inadequate Response to Antidepressants

The purpose of this study is to assess the effect and safety of AZD6765 in patients with major depressive disorder who exhibit inadequate response to antidepressants. AZD6765 is a channel blocker of the N-methyl-D-aspartate (NMDA) class of glutamate receptors.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: AZD6765 iv; Drug: AZD6765 iv; Drug: Placebo

Detailed Description

A Multicenter, Randomized, Double-blind, Parallel Group, Placebo-controlled, Phase IIb Efficacy and Safety Study of Adjunctive AZD6765 in Patients with Major Depressive Disorder (MDD) and a History of Inadequate Response to Antidepressants

• Study Type: Interventional
• Enrollment (Actual): 542
• Phase: Phase 2

Contacts and Locations

Study Locations

• Chile
  • Antofagasta, Chile
    • Research Site
  • Santiago, Chile
    • Research Site
• Slovakia
  • Bratislava, Slovakia
    • Research Site
  • Liptovsky Mikulas, Slovakia
    • Research Site
  • Michalovce Stranany, Slovakia
    • Research Site
  • Rimavska Sobota, Slovakia
    • Research Site
  • Svidnik, Slovakia
    • Research Site
  • Trnava, Slovakia
    • Research Site
• South Africa
  • Cape Town, South Africa
    • Research Site
  • Johannesburg, South Africa
    • Research Site
  • Tygervalley, South Africa
    • Research Site
• United States
  • California
    • Chino, California, United States
      • Research Site
    • Lond Beach, California, United States
      • Research Site
    • San Diego, California, United States
      • Research Site
    • Stanford, California, United States
      • Research Site
  • Connecticut
    • New Heaven, Connecticut, United States
      • Research Site
  • Florida
    • Ft. Lauderdale, Florida, United States
      • Research Site
    • Gainsville, Florida, United States
      • Research Site
    • Lake City, Florida, United States
      • Research Site
    • Miami, Florida, United States
      • Research Site
    • Orlando, Florida, United States
      • Research Site
    • St Petersburg, Florida, United States
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States
      • Research Site
    • Decatur, Georgia, United States
      • Research Site
  • Illinois
    • Hoffman Estates, Illinois, United States
      • Research Site
    • Joliet, Illinois, United States
      • Research Site
    • Skokie, Illinois, United States
      • Research Site
  • Louisiana
    • Lake Charles, Louisiana, United States
      • Research Site
    • Shreveport, Louisiana, United States
      • Research Site
  • Maryland
    • Baltimore, Maryland, United States
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States
      • Research Site
  • Minnesota
    • Minneapolis, Minnesota, United States
      • Research Site
  • Missouri
    • St. Louis, Missouri, United States
      • Research Site
  • New Jersey
    • Willingboro, New Jersey, United States
      • Research Site
  • New York
    • Mount Kisco, New York, United States
      • Research Site
    • New York, New York, United States
      • Research Site
    • Rochester, New York, United States
      • Research Site
  • North Carolina
    • Winston-Salem, North Carolina, United States
      • Research Site
  • Ohio
    • Cincinnati, Ohio, United States
      • Research Site
    • Dayton, Ohio, United States
      • Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States
      • Research Site
  • Texas
    • Dallas, Texas, United States
      • Research Site
    • Houston, Texas, United States
      • Research Site
  • Washington
    • Bellevue, Washington, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Provision of signed and dated informed consent before initiation of any study-related procedures.
• Male or female patients aged 18 to 70 years, inclusive.
• The patient must have a clinical diagnosis of major depressive disorder with a lifetime history of inadequate response to at least 3 antidepressants.
• Women of child-bearing potential must have a negative serum pregnancy test and confirmed use of a highly effective form of birth control before enrollment for a minimum of 3 months before study start.
• Outpatient status at screening and randomization visits.

Exclusion Criteria:

• Patients with a history of diagnosed bipolar disorder or schizophrenia or schizoaffective disorder or currently exhibiting psychotic features associated with their depression; dementia or suspicion thereof.
• Patients who have had a suicide attempt within the last 6 months.
• Electroconvulsive therapy (ECT), vagal nerve stimulation (VNS) or transcranial magnetic stimulation (TMS) or previous treatment with ketamine infusion within the 6 months prior to screening, or any history of deep brain stimulation.
• Patients with any history of seizure disorder (except for febrile seizures in childhood).
• Pregnancy or lactation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: AZD6765 iv; 50 mg (AZD6765 Solution for Infusion, 0.5 mg/mL) by iv infusion.; Drug: AZD6765 iv; 100 mg (AZD6765 Solution for Infusion, 1.0 mg/mL) by iv infusion.
Experimental: 2	Drug: AZD6765 iv; 50 mg (AZD6765 Solution for Infusion, 0.5 mg/mL) by iv infusion.; Drug: AZD6765 iv; 100 mg (AZD6765 Solution for Infusion, 1.0 mg/mL) by iv infusion.
Placebo Comparator: 3	Drug: Placebo; 0.9 sodium chloride [normal saline] solution for injection by iv infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 6 in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score	A 10-item scale for the evaluation of depressive symptoms. Each MADRS item is rated on a 0 to 6 scale. The MADRS total score is calculated as the sum of the 10 individual item scores; the total score can range from 0 to 60. Higher MADRS scores indicate higher levels of depressive symptoms.	Baseline to Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 12 in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score	A 10-item scale for the evaluation of depressive symptoms. Each MADRS item is rated on a 0 to 6 scale. The MADRS total score is calculated as the sum of the 10 individual item scores; the total score can range from 0 to 60. Higher MADRS scores indicate higher levels of depressive symptoms.	Baseline to Week 12
Percentage of Patients With Sustained Response From Week 6 to Week 12 (Defined as ≥50% Reduction From Baseline in the MADRS Total Score at Week 6 and Which is Maintained Through Week 12)	The percentage of patients with with Sustained Response (defined as ≥50% reduction from baseline in the MADRS total score at Week 6 and which is maintained through Week 12) was calculated.	Week 6 to Week 12
Percentage of Patients Who Were Responders (Defined as a ≥50% Reduction From Baseline in MADRS Total Score) at Week 6	The percentage of patients who were Responders (defined as ≥50% reduction from baseline in MADRS total score) was calculated.	Baseline to Week 6
Percentage of Patients Who Were Responders (Defined as a ≥50% Reduction From Baseline in MADRS Total Score) at Week 12	The percentage of patients who were Responders (defined as ≥50% reduction from baseline in MADRS total score) was calculated.	Baseline to Week 12
Percentage of Patients Who Were Remitted (Defined as MADRS Total Score ≤10) at Week 6	The percentage of patients who were Remitted (defined as MADRS total score ≤10) was calculated.	Baseline to Week 6
Percentage of Patients Who Were Remitted (Defined as MADRS Total Score ≤10) at Week 12	The percentage of patients who were Remitted (defined as MADRS total score ≤10) was calculated.	Baseline to Week 12
Change From Baseline in Functional Impairment as Measured by the Change From Baseline in the Sheehan Disability Scale (SDS) Total Score	A 3-item, self-administered scale that measures the extent a patient is impaired by their disease. Higher scores indicate more severe impairment. The SDS total score is calculated as the sum of the score for the 3 intercorrelated domains (school/work, social life, and family life/home responsibilities), ranges from 0 (no impairment) to 30 (most severe impairment).	Baseline to Week 12
Change in Severity of Depressive Symptoms as Measured by Change From Baseline in the Clinical Global Impression-Severity (CGI-S) Score	Clinical Global Impression - Severity (CGI-S) scale rates the severity of the patient's illness at the time of assessment, range from 1 (normal, not ill) to 7 (very severely ill).	Baseline to Week 12
Change in Severity of Depressive Symptoms as Measured by the CGI-I Response (Defined as CGI-I Rating of "Very Much Improved" or "Much Improved") at Week 6	A 3-part, clinician-administered scale that rates the improvement or worsening of the patient's illness from randomization (baseline). Each item is scored on a 1 to 7 scale. CGI-I scores >4 indicate worsening, while scores <4 indicate improvement.	Baseline to Week 6
Change in Severity of Depressive Symptoms as Measured by the CGI-I Response (Defined as CGI-I Rating of "Very Much Improved" or "Much Improved") at Week 12	A 3-part, clinician-administered scale that rates the improvement or worsening of the patient's illness from randomization (baseline). Each item is scored on a 1 to 7 scale. CGI-I scores >4 indicate worsening, while scores <4 indicate improvement.	Baseline to Week 12
Change From Baseline in Self-rated Severity of Depressive Symptoms as Measured by Quick Inventory of Depressive Symptomatology Self-Rated 16-item Scale (QIDS-SR-16) Total Score	A 16-question self-report inventory that includes the 9 Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) criteria symptom domains: sad mood, concentration, self-outlook, suicidal ideation, involvement, energy/fatigability, sleep disturbance (4 items: initial, middle, late insomnia, and hypersomnia), appetite/weight increased or decrease (4 items), and psychomotor agitation/retardation (2 items). The QIDS-SR-16 total scores range from 0 (least severe) to 27 (most severe).	Baseline to Week 12

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Dhaval A Desai, MD, 1800 Concord Pike, Wilmington, DE 19850

Publications and helpful links

Helpful Links

• D6702C00031_Clinical Study Report_Synopsis

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2011
• Primary Completion (Actual): August 26, 2013
• Study Completion (Actual): August 26, 2013

Study Registration Dates

• First Submitted: November 28, 2011
• First Submitted That Met QC Criteria: November 29, 2011
• First Posted (Estimate): November 30, 2011

Study Record Updates

• Last Update Posted (Actual): April 11, 2017
• Last Update Submitted That Met QC Criteria: April 10, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: MDD; Major Depressive Disorder; Inadequate Response to Antidepressant Therapy; Channel blocker of the NMDA class of glutamate receptors
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Pathologic Processes; Mood Disorders; Depression; Depressive Disorder; Disease; Depressive Disorder, Major
• Other Study ID Numbers: D6702C00031; EudraCT number 2011-004690-87