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

Phase 2

Completed

Conditions: Major Depressive Disorder

Interventions: Drug: AZD6765 iv
Drug: Placebo

Registration Number: NCT01482221

Lead Sponsor: AstraZeneca

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

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 542

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2	AZD6765 iv	-
1	AZD6765 iv	-
3	Placebo	-

Primary Outcome Measures

Name	Time	Method
Change From Baseline to Week 6 in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score	Baseline to Week 6	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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline to Week 12 in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score	Baseline to Week 12	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.
Percentage of Patients Who Were Remitted (Defined as MADRS Total Score ≤10) at Week 6	Baseline to Week 6	The percentage of patients who were Remitted (defined as MADRS total score ≤10) was calculated.
Percentage of Patients Who Were Responders (Defined as a ≥50% Reduction From Baseline in MADRS Total Score) at Week 12	Baseline to Week 12	The percentage of patients who were Responders (defined as ≥50% reduction from baseline in MADRS total score) was calculated.
Percentage of Patients Who Were Remitted (Defined as MADRS Total Score ≤10) at Week 12	Baseline to Week 12	The percentage of patients who were Remitted (defined as MADRS total score ≤10) was calculated.
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)	Week 6 to 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.
Change From Baseline in Functional Impairment as Measured by the Change From Baseline in the Sheehan Disability Scale (SDS) Total Score	Baseline to Week 12	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).
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	Baseline to 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.
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	Baseline to 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.
Percentage of Patients Who Were Responders (Defined as a ≥50% Reduction From Baseline in MADRS Total Score) at Week 6	Baseline to Week 6	The percentage of patients who were Responders (defined as ≥50% reduction from baseline in MADRS total score) was calculated.
Change in Severity of Depressive Symptoms as Measured by Change From Baseline in the Clinical Global Impression-Severity (CGI-S) Score	Baseline to Week 12	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).
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	Baseline to Week 12	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).