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

Study Overview
=================
Brief Summary
-----------------
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.

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

Official Title
-----------------
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

Conditions
-----------------
Major Depressive Disorder

Intervention / Treatment
-----------------
* Drug: AZD6765 iv
* Drug: AZD6765 iv
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Major Depressive Disorder, MDD, Inadequate Response to Antidepressant Therapy, Channel blocker of the NMDA class of glutamate receptors