This is a Study to Determine the Antidepressant Effects of AZD6765

Back to results

Primary Purpose

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

AZD6765

Placebo to AZD6765

About this trial

This is an interventional treatment trial for Treatment Resistant Major Depressive Disorder focused on measuring Patients

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients with a diagnosis of Major Depressive Disorder, currently depressed without psychotic features
Females must be of non-childbearing potential.

Exclusion Criteria:

Treatment with Clozapine or ECT within 3 months prior to study
Current or past history of psychotic features or a diagnosis of schizophrenia or any other psychotic disorder as defined in the DSM-IV

Sites / Locations

Research Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

AZD6765 (150 mg) / Placebo

Placebo / AZD6765 (150 mg)

Arm Description

Patients randomized to receive a single intravenous (iv) infusion of AZD6765 (150 mg) over 60 minutes during the first period, followed by a 7-day drug-free period, followed by a single iv infusion of placebo (saline solution) over 60 minutes during the second period.

Patients randomized to receive a single intravenous (iv) infusion of placebo (saline solution) over 60 minutes during the first period, followed by a 7-day drug-free period, followed by a single iv infusion of AZD6765 (150 mg) over 60 minutes during the second period.

Outcomes

Primary Outcome Measures

Montgomery-Asberg Depression Rating Scale (MADRS) Total Score.

Montgomery-Asberg Depression Rating Scale (MADRS) is a 10-item instrument used for the evaluation of depressive symptoms. Each item is rated on a scale of 0 to 6 (with higher scores indicating more severe depression). The individual item scores are added together to form a total score, ranging between 0 and 60. 0 is considered the best score, 60 the worst.

Secondary Outcome Measures

The Number of Participants With Montgomery-Asberg Depression Rating Scale (MADRS) Total Score Less Than 10 (MADRS Remission).

Remission defined as a Montgomery-Asberg Depression Rating Scale (MADRS) total score <10. MADRS is a 10-item instrument used for the evaluation of depressive symptoms. Each item is rated on a scale of 0 to 6 (with higher scores indicating more severe depression). The individual item scores are added together to form a total score, ranging between 0 and 60. 0 is considered the best score, 60 the worst.

The Number of Participants With at Least 50% Reduction in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score (MADRS Response).

Response defined as a >= 50% reduction from baseline in MADRS total score. MADRS is a 10-item instrument used for the evaluation of depressive symptoms. Each item is rated on a scale of 0 to 6 (with higher scores indicating more severe depression). The individual item scores are added together to form a total score, ranging between 0 and 60. 0 is considered the best score, 60 the worst.

Scale for Suicide Ideation (SSI) Total Score.

Scale for Suicide Ideation (SSI) is a 19-item scale designed to quantify the intensity of current conscious suicide ideation. Each item is rated on a scale of 0 to 2 (with higher scores indicating greater suicidal ideation). The individual item scores are added together to form a total score, ranging between 0 and 38. 0 is considered the best outcome, 38 the worst.

Hamilton Anxiety Rating Scale (HAM-A) Total Score.

Hamilton Anxiety Rating Scale (HAM-A) is used as a rating measure of anxiety severity. The scale consists of 14 items. Each item is rated on a scale of 0 to 4. The HAM-A total score is the sum of the 14 items and the score ranges from 0 to 56. 0 is considered the best outcome, 56 the worst.

Hamilton Depression Rating Scale-17 Item (HDRS) Total Score

Hamilton Depression Rating Scale-17 item (HDRS) is a scale that assesses depressive symptoms. HDRS consists of 17 symptoms, each of which is rated from 0 to 2 or 0 to 4, where 0 is none/absent. The total score is calculated as the sum of the 17 individual symptom scores; the total score can range from 0 to 52. Higher scores indicate more severe depression.

Visual Analogue Scale (VAS) Depressed Score

The Visual Analog Scale (VAS) Depressed is a 0 to 100-mm self-administered scale where patients rate their mood between "extreme sad" (0-mm) and "extreme happy" (100-mm), with a median "normal" point.

Clinician-Administered Dissociative States Scale (CADSS) Score.

Clinician- Administered Dissociative States Scale (CADSS) is a clinician-administered measure of perceptual, behavioral, and attentional alterations occurring during dissociative experiences. This scale involves a 23 questions and each is rated from 0 (not at all) to 4 (extremely). The total score is sum of the 23 items and range from 0 to 92 - best is 0 and worst is 92.

Brief Psychiatric Rating Scale (BPRS) Score.

The Brief Psychiatric Rating Scale (BPRS) is a 18-item scale which measures symptoms and behaviors that are characteristic of schizophrenia. Each item is rated from 1 to 7 with higher score indicating greater severity. The total score is the sum of the 18 items, resulting in a range of scores from 18-126. 18 is considered to be the best outcome, 126 the worst.

Beck Depression Inventory (BDI) Score.

Beck Depression Inventory (BDI) is a 21-question instrument for measuring the severity of depression. Each question has a set of at least four possible answer choices, ranging in intensity. A value of 0 to 3 is assigned for each answer and the total score is computed. Higher total scores indicate more severe depressive symptoms.

Young Mania Rating Scale (YMRS) Score.

Young Mania Rating Scale (YMRS) consists of 11 items, rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe) or from 0 (symptom not present) to 4 (symptom extremely severe). The YMRS total score ranges from 0 to 60. 0 is considered to be the best outcome, 60 the worst.

Visual Analogue Scale (VAS) Anxious Score.

The Visual Analog Scale (VAS) Anxious is a 0 to 100-mm self-administered scale where patients rate their mood between "extreme sad" (0-mm) and "extreme happy" (100-mm), with a median "normal" point.

Brief Psychiatric Rating Scale (BPRS) Positive Score.

Brief Psychiatric Rating Scale (BPRS) Positive is a 4-item scale which measures positive symptoms of schizophrenia (conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content). Each item is rated from 1 to 7 with higher score indicating greater severity. The total score is the sum of the 4 items, resulting in a range of scores from 4-28.

Full Information

NCT ID

NCT00986479

First Posted

September 24, 2009

Last Updated

October 15, 2014

Sponsor

AstraZeneca

Collaborators

National Institute of Mental Health (NIMH)

1. Study Identification

Unique Protocol Identification Number

NCT00986479

Brief Title

This is a Study to Determine the Antidepressant Effects of AZD6765

Official Title

An Investigation of the Antidepressant Effects of an NMDA Antagonist in Treatment-Resistant Major Depression

Study Type

Interventional

2. Study Status

Record Verification Date

October 2014

Overall Recruitment Status

Completed

Study Start Date

December 2009 (undefined)

Primary Completion Date

December 2011 (Actual)

Study Completion Date

December 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AstraZeneca

Collaborators

National Institute of Mental Health (NIMH)

4. Oversight

Data Monitoring Committee

No

5. Study Description

Brief Summary

The purpose of this study is to determine the antidepressant effects of AZD6765 compared to placebo.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Treatment Resistant Major Depressive Disorder

Keywords

Patients

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Crossover Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

22 (Actual)

8. Arms, Groups, and Interventions

Arm Title

AZD6765 (150 mg) / Placebo

Arm Type

Experimental

Arm Description

Patients randomized to receive a single intravenous (iv) infusion of AZD6765 (150 mg) over 60 minutes during the first period, followed by a 7-day drug-free period, followed by a single iv infusion of placebo (saline solution) over 60 minutes during the second period.

Arm Title

Placebo / AZD6765 (150 mg)

Arm Type

Placebo Comparator

Arm Description

Patients randomized to receive a single intravenous (iv) infusion of placebo (saline solution) over 60 minutes during the first period, followed by a 7-day drug-free period, followed by a single iv infusion of AZD6765 (150 mg) over 60 minutes during the second period.

Intervention Type

Drug

Intervention Name(s)

AZD6765

Intervention Description

Single IV infusion of 150 mg AZD6765.

Intervention Type

Drug

Intervention Name(s)

Placebo to AZD6765

Intervention Description

Single IV infusion of Placebo to AZD6765

Primary Outcome Measure Information:

Title

Montgomery-Asberg Depression Rating Scale (MADRS) Total Score.

Description

Montgomery-Asberg Depression Rating Scale (MADRS) is a 10-item instrument used for the evaluation of depressive symptoms. Each item is rated on a scale of 0 to 6 (with higher scores indicating more severe depression). The individual item scores are added together to form a total score, ranging between 0 and 60. 0 is considered the best score, 60 the worst.

Time Frame

60 minutes (min) prior to dosing (baseline); and 60 min, 80 min, 110 min, 230 min, 1 day, 2 days, 3 days and 7 days following dosing.

Secondary Outcome Measure Information:

Title

The Number of Participants With Montgomery-Asberg Depression Rating Scale (MADRS) Total Score Less Than 10 (MADRS Remission).

Description

Remission defined as a Montgomery-Asberg Depression Rating Scale (MADRS) total score <10. MADRS is a 10-item instrument used for the evaluation of depressive symptoms. Each item is rated on a scale of 0 to 6 (with higher scores indicating more severe depression). The individual item scores are added together to form a total score, ranging between 0 and 60. 0 is considered the best score, 60 the worst.

Time Frame

60 minutes (min) prior to dosing (baseline); and 60 min, 80 min, 110 min, 230 min, 1 day, 2 days, 3 days and 7 days following dosing.

Title

The Number of Participants With at Least 50% Reduction in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score (MADRS Response).

Description

Response defined as a >= 50% reduction from baseline in MADRS total score. MADRS is a 10-item instrument used for the evaluation of depressive symptoms. Each item is rated on a scale of 0 to 6 (with higher scores indicating more severe depression). The individual item scores are added together to form a total score, ranging between 0 and 60. 0 is considered the best score, 60 the worst.

Time Frame

60 minutes (min) prior to dosing (baseline); and 60 min, 80 min, 110 min, 230 min, 1 day, 2 days, 3 days and 7 days following dosing.

Title

Scale for Suicide Ideation (SSI) Total Score.

Description

Scale for Suicide Ideation (SSI) is a 19-item scale designed to quantify the intensity of current conscious suicide ideation. Each item is rated on a scale of 0 to 2 (with higher scores indicating greater suicidal ideation). The individual item scores are added together to form a total score, ranging between 0 and 38. 0 is considered the best outcome, 38 the worst.

Time Frame

60 minutes (min) prior to dosing (baseline); and 60 min, 80 min, 110 min, 230 min, 1 day, 2 days, 3 days and 7 days following dosing.

Title

Hamilton Anxiety Rating Scale (HAM-A) Total Score.

Description

Hamilton Anxiety Rating Scale (HAM-A) is used as a rating measure of anxiety severity. The scale consists of 14 items. Each item is rated on a scale of 0 to 4. The HAM-A total score is the sum of the 14 items and the score ranges from 0 to 56. 0 is considered the best outcome, 56 the worst.

Time Frame

60 minutes (min) prior to dosing (baseline); and 230 min, 1 day, 2 days, 3 days and 7 days following dosing.

Title

Hamilton Depression Rating Scale-17 Item (HDRS) Total Score

Description

Hamilton Depression Rating Scale-17 item (HDRS) is a scale that assesses depressive symptoms. HDRS consists of 17 symptoms, each of which is rated from 0 to 2 or 0 to 4, where 0 is none/absent. The total score is calculated as the sum of the 17 individual symptom scores; the total score can range from 0 to 52. Higher scores indicate more severe depression.

Time Frame

60 minutes (min) prior to dosing (baseline); and 60 min, 80 min, 110 min, 230 min, 1 day, 2 days, 3 days and 7 days following dosing

Title

Visual Analogue Scale (VAS) Depressed Score

Description

The Visual Analog Scale (VAS) Depressed is a 0 to 100-mm self-administered scale where patients rate their mood between "extreme sad" (0-mm) and "extreme happy" (100-mm), with a median "normal" point.

Time Frame

60 minutes (min) prior to dosing (baseline); and 60 min, 80 min, 110 min, 230 min, 1 day, 2 days, 3 days and 7 days following dosing

Title

Clinician-Administered Dissociative States Scale (CADSS) Score.

Description

Clinician- Administered Dissociative States Scale (CADSS) is a clinician-administered measure of perceptual, behavioral, and attentional alterations occurring during dissociative experiences. This scale involves a 23 questions and each is rated from 0 (not at all) to 4 (extremely). The total score is sum of the 23 items and range from 0 to 92 - best is 0 and worst is 92.

Time Frame

60 minutes (min) prior to dosing (baseline); and 60 min, 80 min, 110 min, 230 min, 1 day, 2 days, 3 days and 7 days following dosing

Title

Brief Psychiatric Rating Scale (BPRS) Score.

Description

The Brief Psychiatric Rating Scale (BPRS) is a 18-item scale which measures symptoms and behaviors that are characteristic of schizophrenia. Each item is rated from 1 to 7 with higher score indicating greater severity. The total score is the sum of the 18 items, resulting in a range of scores from 18-126. 18 is considered to be the best outcome, 126 the worst.

Time Frame

60 minutes (min) prior to dosing (baseline); and 60 min, 80 min, 110 min, 230 min, 1 day, 2 days, 3 days and 7 days following dosing.

Title

Beck Depression Inventory (BDI) Score.

Description

Beck Depression Inventory (BDI) is a 21-question instrument for measuring the severity of depression. Each question has a set of at least four possible answer choices, ranging in intensity. A value of 0 to 3 is assigned for each answer and the total score is computed. Higher total scores indicate more severe depressive symptoms.

Time Frame

60 minutes (min) prior to dosing (baseline); and 60 min, 80 min, 110 min, 230 min, 1 day, 2 days, 3 days and 7 days following dosing.

Title

Young Mania Rating Scale (YMRS) Score.

Description

Young Mania Rating Scale (YMRS) consists of 11 items, rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe) or from 0 (symptom not present) to 4 (symptom extremely severe). The YMRS total score ranges from 0 to 60. 0 is considered to be the best outcome, 60 the worst.

Time Frame

60 minutes (min) prior to dosing (baseline); and 60 min, 80 min, 110 min, 230 min, 1 day, 2 days, 3 days and 7 days following dosing.

Title

Visual Analogue Scale (VAS) Anxious Score.

Description

The Visual Analog Scale (VAS) Anxious is a 0 to 100-mm self-administered scale where patients rate their mood between "extreme sad" (0-mm) and "extreme happy" (100-mm), with a median "normal" point.

Time Frame

60 minutes (min) prior to dosing (baseline); and 60 min, 80 min, 110 min, 230 min, 1 day, 2 days, 3 days and 7 days following dosing.

Title

Brief Psychiatric Rating Scale (BPRS) Positive Score.

Description

Brief Psychiatric Rating Scale (BPRS) Positive is a 4-item scale which measures positive symptoms of schizophrenia (conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content). Each item is rated from 1 to 7 with higher score indicating greater severity. The total score is the sum of the 4 items, resulting in a range of scores from 4-28.

Time Frame

60 minutes (min) prior to dosing (baseline); and 60 min, 80 min, 110 min, 230 min, 1 day, 2 days, 3 days and 7 days following dosing.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria: Patients with a diagnosis of Major Depressive Disorder, currently depressed without psychotic features Females must be of non-childbearing potential. Exclusion Criteria: Treatment with Clozapine or ECT within 3 months prior to study Current or past history of psychotic features or a diagnosis of schizophrenia or any other psychotic disorder as defined in the DSM-IV

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Carlos A Zarate, MD

Organizational Affiliation

National Institute of Mental Health (NIMH)

Official's Role

Principal Investigator

Facility Information:

Facility Name

Research Site

City

Bethesda

State/Province

Maryland

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

34510411

Citation

Dean RL, Hurducas C, Hawton K, Spyridi S, Cowen PJ, Hollingsworth S, Marquardt T, Barnes A, Smith R, McShane R, Turner EH, Cipriani A. Ketamine and other glutamate receptor modulators for depression in adults with unipolar major depressive disorder. Cochrane Database Syst Rev. 2021 Sep 12;9(9):CD011612. doi: 10.1002/14651858.CD011612.pub3.

Results Reference

derived

PubMed Identifier

27914292

Citation

Lepow L, Luckenbaugh DA, Park L, Henter ID, Zarate CA Jr. Case series: Antidepressant effects of low-affinity and low-trapping NMDA receptor antagonists did not predict response to ketamine in seven subjects. J Psychiatr Res. 2017 Mar;86:55-57. doi: 10.1016/j.jpsychires.2016.10.023. Epub 2016 Nov 22. No abstract available.

Results Reference

derived

PubMed Identifier

23206319

Citation

Zarate CA Jr, Mathews D, Ibrahim L, Chaves JF, Marquardt C, Ukoh I, Jolkovsky L, Brutsche NE, Smith MA, Luckenbaugh DA. A randomized trial of a low-trapping nonselective N-methyl-D-aspartate channel blocker in major depression. Biol Psychiatry. 2013 Aug 15;74(4):257-64. doi: 10.1016/j.biopsych.2012.10.019. Epub 2012 Dec 1.

Results Reference

derived

Links:

URL

http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=213&filename=D6702C00015_Clinical_Study_Report_Synopsis.pdf

Description

D6702C00015 Clinical Study Report Synopsis

Treatment Resistant Major Depressive Disorder

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial