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Trial record 64 of 1906 for:    "Depressive Disorder" [DISEASE] AND Rating AND Major Depressive Disorder AND Depressive Disorder, Major

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01482221
Recruitment Status : Completed
First Posted : November 30, 2011
Results First Posted : April 11, 2017
Last Update Posted : April 11, 2017
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Major Depressive Disorder
Interventions Drug: AZD6765 iv
Drug: Placebo
Enrollment 542
Recruitment Details This multicenter study was conducted in Chile, Slovakia, South Africa, and the United States between 16 December 2011 and 26 August 2013. A total of 542 patients were enrolled in the study and of these, 302 patients were randomized to treatment. 240 patients were not randomized to treatment due to eligibility criteria not being fulfilled.
Pre-assignment Details The study had a screening/washout period of up to 42 days, a 12-week double blind treatment period, and a 14-day follow-up period. Patients received 3 infusions per week during Weeks 1 to 3,1 infusion per week during Weeks 4 to 6, and 1 infusion every other week during Weeks 7 to 12.
Arm/Group Title AZD6765 50 mg AZD6765 100 mg Placebo
Hide Arm/Group Description Intravenous infusion Intravenous infusion Intravenous infusion
Period Title: Overall Study
Started 101 101 100
Completed 80 81 77
Not Completed 21 20 23
Reason Not Completed
Lack of Efficacy             1             0             1
Lost to Follow-up             3             2             1
Study-Specific Withdrawal Criteria             2             0             1
Condition under Investigation Worsened             3             2             4
Severe Non-Compliance to Protocol             1             0             1
Adverse Event             1             7             3
Withdrawal by Subject             10             7             12
Incorrect randomization             0             1             0
Physician Decision             0             1             0
Arm/Group Title AZD6765 50 mg AZD6765 100 mg Placebo Total
Hide Arm/Group Description Intravenous infusion Intravenous infusion Intravenous infusion Total of all reporting groups
Overall Number of Baseline Participants 101 101 100 302
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 101 participants 101 participants 100 participants 302 participants
47.7  (11.19) 47.5  (11.89) 49.5  (11.12) 48.2  (11.40)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 101 participants 101 participants 100 participants 302 participants
Female
62
  61.4%
70
  69.3%
65
  65.0%
197
  65.2%
Male
39
  38.6%
31
  30.7%
35
  35.0%
105
  34.8%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 101 participants 101 participants 100 participants 302 participants
White 91 87 91 269
Black or African American 8 11 6 25
Asian 0 3 1 4
Other 2 0 2 4
1.Primary Outcome
Title Change From Baseline to Week 6 in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Hide Description 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.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
The modified intent-to-treat (mITT) analysis set included all randomized patients, who took investigational product (IP) and who have a non-missing baseline MADRS total score and at least 1 post-baseline MADRS total score, classified according to their randomized treatment.
Arm/Group Title AZD6765 50 mg AZD6765 100 mg Placebo
Hide Arm/Group Description:
Intravenous infusion
Intravenous infusion
Intravenous infusion
Overall Number of Participants Analyzed 101 100 97
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-14.37  (1.238) -14.40  (1.244) -13.18  (1.266)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZD6765 50 mg, Placebo
Comments Mixed model repeated measures (MMRM) includes treatment, pooled center, visit, treatment by visit interaction, and baseline MADRS score by visit interaction as explanatory variables. Treatment, visit, treatment by visit interaction, and baseline MADRS score by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.630
Comments The adjusted p-values protect the overall family-wise error rate across the 6 key comparisons of AZD6765 100 mg and 50 mg to placebo (for MADRS change from baseline to 6 weeks and to 12 weeks and for Sustained Response).
Method Mixed models for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -1.18
Confidence Interval (2-Sided) 95%
-4.519 to 2.152
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.695
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection AZD6765 100 mg, Placebo
Comments MMRM includes treatment, pooled center, visit, treatment by visit interaction, and baseline MADRS score by visit interaction as explanatory variables. Treatment, visit, treatment by visit interaction, and baseline MADRS score by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.476
Comments The adjusted p-values protect the overall family-wise error rate across the 6 key comparisons of AZD6765 100 mg and 50 mg to placebo (for MADRS change from baseline to 6 weeks and to 12 weeks and for Sustained Response).
Method Mixed models for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -1.21
Confidence Interval (2-Sided) 95%
-4.563 to 2.134
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.701
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline to Week 12 in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Hide Description 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.
Time Frame Baseline to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The modified intent-to-treat (mITT) analysis set included all randomized patients, who took IP and who have a non-missing baseline MADRS total score and at least 1 post-baseline MADRS total score, classified according to their randomized treatment.
Arm/Group Title AZD6765 50 mg AZD6765 100 mg Placebo
Hide Arm/Group Description:
Intravenous infusion
Intravenous infusion
Intravenous infusion
Overall Number of Participants Analyzed 101 100 97
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-15.97  (1.313) -13.03  (1.332) -13.92  (1.354)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZD6765 50 mg, Placebo
Comments Mixed model repeated measures (MMRM) includes treatment, pooled center, visit, treatment by visit interaction, and baseline MADRS score by visit interaction as explanatory variables. Treatment, visit, treatment by visit interaction, and baseline MADRS score by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.630
Comments The adjusted p-values protect the overall family-wise error rate across the 6 key comparisons of AZD6765 100 mg and 50 mg to placebo (for MADRS change from baseline to 6 weeks and to 12 weeks and for Sustained Response).
Method Mixed models for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -2.05
Confidence Interval (2-Sided) 95%
-5.628 to 1.522
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.816
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection AZD6765 100 mg, Placebo
Comments MMRM includes treatment, pooled center, visit, treatment by visit interaction, and baseline MADRS score by visit interaction as explanatory variables. Treatment, visit, treatment by visit interaction, and baseline MADRS score by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.630
Comments The adjusted p-values protect the overall family-wise error rate across the 6 key comparisons of AZD6765 100 mg and 50 mg to placebo (for MADRS change from baseline to 6 weeks and to 12 weeks and for Sustained Response).
Method Mixed models for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.88
Confidence Interval (2-Sided) 95%
-2.720 to 4.485
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.830
Estimation Comments [Not Specified]
3.Secondary Outcome
Title 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)
Hide Description 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.
Time Frame Week 6 to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT analysis set included all randomized patients, who took IP and who have a non-missing baseline MADRS total score and at least 1 post-baseline MADRS total score, classified according to their randomized treatment.
Arm/Group Title AZD6765 50 mg AZD6765 100 mg Placebo
Hide Arm/Group Description:
Intravenous infusion
Intravenous infusion
Intravenous infusion
Overall Number of Participants Analyzed 101 100 97
Measure Type: Number
Unit of Measure: percentage of participants analyzed
22.8 23.0 21.6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZD6765 50 mg, Placebo
Comments Logistic regression model including treatment as a fixed effect and the baseline MADRS total score as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.852
Comments The adjusted p-values protect the overall family-wise error rate across the 6 key comparisons of AZD6765 100 mg and 50 mg to placebo (for MADRS change from baseline to 6 weeks and to 12 weeks and for Sustained Response).
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.07
Confidence Interval (2-Sided) 95%
0.544 to 2.089
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.366
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection AZD6765 100 mg, Placebo
Comments Logistic regression model including treatment as a fixed effect and the baseline MADRS total score as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.821
Comments The adjusted p-values protect the overall family-wise error rate across the 6 key comparisons of AZD6765 100 mg and 50 mg to placebo (for MADRS change from baseline to 6 weeks and to 12 weeks and for Sustained Response).
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.08
Confidence Interval (2-Sided) 95%
0.552 to 2.115
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.370
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Patients Who Were Responders (Defined as a ≥50% Reduction From Baseline in MADRS Total Score) at Week 6
Hide Description The percentage of patients who were Responders (defined as ≥50% reduction from baseline in MADRS total score) was calculated.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT analysis set included all randomized patients, who took IP and who have a non-missing baseline MADRS total score and at least 1 post-baseline MADRS total score, classified according to their randomized treatment.
Arm/Group Title AZD6765 50 mg AZD6765 100 mg Placebo
Hide Arm/Group Description:
Intravenous infusion
Intravenous infusion
Intravenous infusion
Overall Number of Participants Analyzed 86 84 82
Measure Type: Number
Unit of Measure: percentage of participants analyzed
36.0 44.0 39.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZD6765 50 mg, Placebo
Comments Generalized linear model of the repeated measures (GEE) with logic link including treatment, visit, and treatment by visit interaction as fixed effects and the baseline MADRS total score as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.751
Comments [Not Specified]
Method GEE for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
0.485 to 1.686
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.318
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection AZD6765 100 mg, Placebo
Comments Generalized linear model of the repeated measures (GEE) with logic link including treatment, visit, and treatment by visit interaction as fixed effects and the baseline MADRS total score as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.555
Comments [Not Specified]
Method GEE for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.20
Confidence Interval (2-Sided) 95%
0.650 to 2.233
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.315
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Patients Who Were Responders (Defined as a ≥50% Reduction From Baseline in MADRS Total Score) at Week 12
Hide Description The percentage of patients who were Responders (defined as ≥50% reduction from baseline in MADRS total score) was calculated.
Time Frame Baseline to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT analysis set included all randomized patients, who took IP and who have a non-missing baseline MADRS total score and at least 1 post-baseline MADRS total score, classified according to their randomized treatment.
Arm/Group Title AZD6765 50 mg AZD6765 100 mg Placebo
Hide Arm/Group Description:
Intravenous infusion
Intravenous infusion
Intravenous infusion
Overall Number of Participants Analyzed 89 85 81
Measure Type: Number
Unit of Measure: percentage of participants analyzed
48.3 36.5 40.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZD6765 50 mg, Placebo
Comments Generalized linear model of the repeated measures (GEE) with logic link including treatment, visit, and treatment by visit interaction as fixed effects and the baseline MADRS total score as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.434
Comments [Not Specified]
Method GEE for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.27
Confidence Interval (2-Sided) 95%
0.699 to 2.301
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.304
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection AZD6765 100 mg, Placebo
Comments Generalized linear model of the repeated measures (GEE) with logic link including treatment, visit, and treatment by visit interaction as fixed effects and the baseline MADRS total score as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.286
Comments [Not Specified]
Method GEE for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.71
Confidence Interval (2-Sided) 95%
0.377 to 1.334
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.322
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Percentage of Patients Who Were Remitted (Defined as MADRS Total Score ≤10) at Week 6
Hide Description The percentage of patients who were Remitted (defined as MADRS total score ≤10) was calculated.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT analysis set included all randomized patients, who took IP and who have a non-missing baseline MADRS total score and at least 1 post-baseline MADRS total score, classified according to their randomized treatment.
Arm/Group Title AZD6765 50 mg AZD6765 100 mg Placebo
Hide Arm/Group Description:
Intravenous infusion
Intravenous infusion
Intravenous infusion
Overall Number of Participants Analyzed 86 84 82
Measure Type: Number
Unit of Measure: percentage of participants analyzed
23.3 23.8 18.3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZD6765 50 mg, Placebo
Comments Generalized linear model of the repeated measures (GEE) with logic link including treatment, visit, and treatment by visit interaction as fixed effects and the baseline MADRS total score as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.357
Comments [Not Specified]
Method GEE for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.42
Confidence Interval (2-Sided) 95%
0.672 to 3.007
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.382
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection AZD6765 100 mg, Placebo
Comments Generalized linear model of the repeated measures (GEE) with logic link including treatment, visit, and treatment by visit interaction as fixed effects and the baseline MADRS total score as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.463
Comments [Not Specified]
Method GEE for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.33
Confidence Interval (2-Sided) 95%
0.622 to 2.840
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.387
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Percentage of Patients Who Were Remitted (Defined as MADRS Total Score ≤10) at Week 12
Hide Description The percentage of patients who were Remitted (defined as MADRS total score ≤10) was calculated.
Time Frame Baseline to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT analysis set included all randomized patients, who took IP and who have a non-missing baseline MADRS total score and at least 1 post-baseline MADRS total score, classified according to their randomized treatment.
Arm/Group Title AZD6765 50 mg AZD6765 100 mg Placebo
Hide Arm/Group Description:
Intravenous infusion
Intravenous infusion
Intravenous infusion
Overall Number of Participants Analyzed 89 85 81
Measure Type: Number
Unit of Measure: percentage of participants analyzed
27.0 22.4 25.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZD6765 50 mg, Placebo
Comments Generalized linear model of the repeated measures (GEE) with logic link including treatment, visit, and treatment by visit interaction as fixed effects and the baseline MADRS total score as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.911
Comments [Not Specified]
Method GEE for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.04
Confidence Interval (2-Sided) 95%
0.532 to 2.031
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.342
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection AZD6765 100 mg, Placebo
Comments Generalized linear model of the repeated measures (GEE) with logic link including treatment, visit, and treatment by visit interaction as fixed effects and the baseline MADRS total score as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.509
Comments [Not Specified]
Method GEE for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.78
Confidence Interval (2-Sided) 95%
0.382 to 1.613
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.368
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change From Baseline in Functional Impairment as Measured by the Change From Baseline in the Sheehan Disability Scale (SDS) Total Score
Hide Description 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).
Time Frame Baseline to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT analysis set included all randomized patients, who took IP and who have a non-missing baseline MADRS total score and at least 1 post-baseline MADRS total score, classified according to their randomized treatment.
Arm/Group Title AZD6765 50 mg AZD6765 100 mg Placebo
Hide Arm/Group Description:
Intravenous infusion
Intravenous infusion
Intravenous infusion
Overall Number of Participants Analyzed 101 100 97
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Week 6 -7.08  (0.959) -6.90  (0.981) -6.91  (0.989)
Week 12 -6.98  (0.995) -6.80  (1.021) -8.09  (1.034)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZD6765 50 mg, Placebo
Comments MMRM includes treatment, pooled center, visit, treatment by visit interaction, and baseline SDS score by visit interaction as explanatory variables. Treatment, visit, treatment by visit interaction, and baseline SDS score by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.889
Comments Analysis for change in SDS total score from baseline to Week 6
Method Mixed models for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.17
Confidence Interval (2-Sided) 95%
-2.609 to 2.264
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.238
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection AZD6765 100 mg, Placebo
Comments MMRM includes treatment, pooled center, visit, treatment by visit interaction, and baseline SDS score by visit interaction as explanatory variables. Treatment, visit, treatment by visit interaction, and baseline SDS score by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.992
Comments Analysis for change in SDS total score from baseline to Week 6
Method Mixed models for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.01
Confidence Interval (2-Sided) 95%
-2.477 to 2.501
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.264
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection AZD6765 50 mg, Placebo
Comments MMRM includes treatment, pooled center, visit, treatment by visit interaction, and baseline SDS score by visit interaction as explanatory variables. Treatment, visit, treatment by visit interaction, and baseline SDS score by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.392
Comments Analysis for change in SDS total score from baseline to Week 12
Method Mixed models for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 1.11
Confidence Interval (2-Sided) 95%
-1.448 to 3.678
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.301
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection AZD6765 100 mg, Placebo
Comments MMRM includes treatment, pooled center, visit, treatment by visit interaction, and baseline SDS score by visit interaction as explanatory variables. Treatment, visit, treatment by visit interaction, and baseline SDS score by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.333
Comments Analysis for changed in SDS total score from baseline to Week 12
Method Mixed models for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 1.29
Confidence Interval (2-Sided) 95%
-1.327 to 3.908
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.329
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Change in Severity of Depressive Symptoms as Measured by Change From Baseline in the Clinical Global Impression-Severity (CGI-S) Score
Time Frame Baseline to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT analysis set included all randomized patients, who took IP and who have a non-missing baseline MADRS total score and at least 1 post-baseline MADRS total score, classified according to their randomized treatment.
Arm/Group Title AZD6765 50 mg AZD6765 100 mg Placebo
Hide Arm/Group Description:
Intravenous infusion
Intravenous infusion
Intravenous infusion
Overall Number of Participants Analyzed 101 100 97
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Week 6 -1.5  (0.16) -1.5  (0.16) -1.4  (0.16)
Week 12 -1.8  (0.16) -1.5  (0.16) -1.6  (0.16)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZD6765 50 mg, Placebo
Comments MMRM includes treatment, pooled center, visit, treatment by visit interaction, and baseline CGI-S score by visit interaction as explanatory variables. Treatment, visit, treatment by visit interaction, and baseline CGI-S score by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.728
Comments Analysis for change in CGI-S total score from baseline to Week 6
Method Mixed models for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.49 to 0.34
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.21
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection AZD6765 100 mg, Placebo
Comments MMRM includes treatment, pooled center, visit, treatment by visit interaction, and baseline CGI-S score by visit interaction as explanatory variables. Treatment, visit, treatment by visit interaction, and baseline CGI-S score by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.562
Comments Analysis for change in CGI-S total score from baseline to Week 6
Method Mixed models for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.54 to 0.29
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.21
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection AZD6765 50 mg, Placebo
Comments MMRM includes treatment, pooled center, visit, treatment by visit interaction, and baseline CGI-S score by visit interaction as explanatory variables. Treatment, visit, treatment by visit interaction, and baseline CGI-S score by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.283
Comments Analysis for change in CGI-S total score from baseline to Week 12
Method Mixed models for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-0.64 to 0.19
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.21
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection AZD6765 100 mg, Placebo
Comments MMRM includes treatment, pooled center, visit, treatment by visit interaction, and baseline CGI-S score by visit interaction as explanatory variables. Treatment, visit, treatment by visit interaction, and baseline CGI-S score by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.540
Comments Analysis for changed in CGI-S total score from baseline to Week 12
Method Mixed models for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.29 to 0.55
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.21
Estimation Comments [Not Specified]
10.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT analysis set included all randomized patients, who took IP and who have a non-missing baseline MADRS total score and at least 1 post-baseline MADRS total score, classified according to their randomized treatment.
Arm/Group Title AZD6765 50 mg AZD6765 100 mg Placebo
Hide Arm/Group Description:
Intravenous infusion
Intravenous infusion
Intravenous infusion
Overall Number of Participants Analyzed 86 84 82
Measure Type: Number
Unit of Measure: percentage of participants analyzed
51.2 47.6 37.8
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZD6765 50 mg, Placebo
Comments Generalized linear model of the repeated measures (GEE) with logic link including treatment, visit, and treatment by visit interaction as fixed effects and the baseline CGI-S total score as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.067
Comments [Not Specified]
Method GEE for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.74
Confidence Interval (2-Sided) 95%
0.962 to 3.141
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.302
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection AZD6765 100 mg, Placebo
Comments Generalized linear model of the repeated measures (GEE) with logic link including treatment, visit, and treatment by visit interaction as fixed effects and the baseline CGI-S total score as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.230
Comments [Not Specified]
Method GEE for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.43
Confidence Interval (2-Sided) 95%
0.798 to 2.558
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.297
Estimation Comments [Not Specified]
11.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Baseline to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT analysis set included all randomized patients, who took IP and who have a non-missing baseline MADRS total score and at least 1 post-baseline MADRS total score, classified according to their randomized treatment.
Arm/Group Title AZD6765 50 mg AZD6765 100 mg Placebo
Hide Arm/Group Description:
Intravenous infusion
Intravenous infusion
Intravenous infusion
Overall Number of Participants Analyzed 89 85 81
Measure Type: Number
Unit of Measure: percentage of participants analyzed
50.6 44.7 40.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZD6765 50 mg, Placebo
Comments Generalized linear model of the repeated measures (GEE) with logic link including treatment, visit, and treatment by visit interaction as fixed effects and the baseline CGI-S total score as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.268
Comments [Not Specified]
Method GEE for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.38
Confidence Interval (2-Sided) 95%
0.780 to 2.447
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.292
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection AZD6765 100 mg, Placebo
Comments Generalized linear model of the repeated measures (GEE) with logic link including treatment, visit, and treatment by visit interaction as fixed effects and the baseline CGI-S total score as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.909
Comments [Not Specified]
Method GEE for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.97
Confidence Interval (2-Sided) 95%
0.533 to 1.750
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.303
Estimation Comments [Not Specified]
12.Secondary Outcome
Title 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
Hide Description 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).
Time Frame Baseline to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT analysis set included all randomized patients, who took IP and who have a non-missing baseline MADRS total score and at least 1 post-baseline MADRS total score, classified according to their randomized treatment.
Arm/Group Title AZD6765 50 mg AZD6765 100 mg Placebo
Hide Arm/Group Description:
Intravenous infusion
Intravenous infusion
Intravenous infusion
Overall Number of Participants Analyzed 101 100 97
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Week 6 -8.7  (0.69) -7.9  (0.70) -8.1  (0.71)
Week 12 -9.2  (0.70) -7.6  (0.71) -8.9  (0.72)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZD6765 50 mg, Placebo
Comments MMRM includes treatment, pooled center, visit, treatment by visit interaction, and baseline QIDS-SR-16 total score by visit interaction as explanatory variables. Treatment, visit, treatment by visit interaction, and baseline QIDS-SR-16 total score by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.505
Comments Analysis for change in QIDS-SR-16 total score from baseline to Week 6
Method Mixed models for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-2.29 to 1.13
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.87
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection AZD6765 100 mg, Placebo
Comments MMRM includes treatment, pooled center, visit, treatment by visit interaction, and baseline QIDS-SR-16 total score by visit interaction as explanatory variables. Treatment, visit, treatment by visit interaction, and baseline QIDS-SR-16 total score by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.842
Comments Analysis for change in QIDS-SR-16 total score from baseline to Week 6
Method Mixed models for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-1.56 to 1.91
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.88
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection AZD6765 50 mg, Placebo
Comments MMRM includes treatment, pooled center, visit, treatment by visit interaction, and baseline QIDS-SR-16 total score by visit interaction as explanatory variables. Treatment, visit, treatment by visit interaction, and baseline QIDS-SR-16 total score by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.788
Comments Analysis for change in QIDS-SR-16 total score from baseline to Week 12
Method Mixed models for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-1.98 to 1.51
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.89
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection AZD6765 100 mg, Placebo
Comments MMRM includes treatment, pooled center, visit, treatment by visit interaction, and baseline QIDS-SR-16 total score by visit interaction as explanatory variables. Treatment, visit, treatment by visit interaction, and baseline QIDS-SR-16 total score by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.133
Comments Analysis for changed in QIDS-SR-16 total score from baseline to Week 12
Method Mixed models for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 1.4
Confidence Interval (2-Sided) 95%
-0.42 to 3.12
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.90
Estimation Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description The AZD6765iv (intravenous) 100 mg group had one less subject than the numbers provided in the Participant Flow Module because one subject who was randomized did not receive any study medication and thus was excluded from the efficacy and safety analysis sets.
 
Arm/Group Title AZD6765iv 100 mg AZD6765iv 50 mg Placebo
Hide Arm/Group Description Intravenous infusion Intravenous infusion Intravenous infusion
All-Cause Mortality
AZD6765iv 100 mg AZD6765iv 50 mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
AZD6765iv 100 mg AZD6765iv 50 mg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/100 (4.00%)      2/101 (1.98%)      4/100 (4.00%)    
Blood and lymphatic system disorders       
ANAEMIA  1  0/100 (0.00%)  0 1/101 (0.99%)  1 0/100 (0.00%)  0
General disorders       
NON-CARDIAC CHEST PAIN  1  0/100 (0.00%)  0 0/101 (0.00%)  0 1/100 (1.00%)  1
Infections and infestations       
HEPATITIS C  1  1/100 (1.00%)  1 0/101 (0.00%)  0 0/100 (0.00%)  0
Injury, poisoning and procedural complications       
ALCOHOL POISONING  1  0/100 (0.00%)  0 0/101 (0.00%)  0 1/100 (1.00%)  1
Psychiatric disorders       
DEPRESSIVE SYMPTOM  1  1/100 (1.00%)  1 0/101 (0.00%)  0 0/100 (0.00%)  0
INTENTIONAL DRUG MISUSE  1  1/100 (1.00%)  1 0/101 (0.00%)  0 0/100 (0.00%)  0
MAJOR DEPRESSION  1  1/100 (1.00%)  1 0/101 (0.00%)  0 0/100 (0.00%)  0
SUICIDAL IDEATION  1  0/100 (0.00%)  0 0/101 (0.00%)  0 1/100 (1.00%)  1
SUICIDE ATTEMPT  1  0/100 (0.00%)  0 0/101 (0.00%)  0 1/100 (1.00%)  1
Respiratory, thoracic and mediastinal disorders       
ASTHMA  1  0/100 (0.00%)  0 1/101 (0.99%)  1 0/100 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
AZD6765iv 100 mg AZD6765iv 50 mg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   68/100 (68.00%)      59/101 (58.42%)      47/100 (47.00%)    
Gastrointestinal disorders       
CONSTIPATION  1  6/100 (6.00%)  6 2/101 (1.98%)  2 5/100 (5.00%)  5
DIARRHOEA  1  5/100 (5.00%)  7 7/101 (6.93%)  10 5/100 (5.00%)  6
DRY MOUTH  1  6/100 (6.00%)  17 3/101 (2.97%)  5 2/100 (2.00%)  3
NAUSEA  1  21/100 (21.00%)  26 13/101 (12.87%)  13 13/100 (13.00%)  16
General disorders       
FATIGUE  1  6/100 (6.00%)  6 5/101 (4.95%)  6 5/100 (5.00%)  6
FEELING DRUNK  1  6/100 (6.00%)  38 1/101 (0.99%)  1 0/100 (0.00%)  0
Infections and infestations       
UPPER RESPIRATORY TRACT INFECTION  1  6/100 (6.00%)  7 7/101 (6.93%)  8 4/100 (4.00%)  4
Musculoskeletal and connective tissue disorders       
BACK PAIN  1  1/100 (1.00%)  1 7/101 (6.93%)  9 2/100 (2.00%)  2
Nervous system disorders       
DIZZINESS  1  45/100 (45.00%)  205 27/101 (26.73%)  63 10/100 (10.00%)  17
HEADACHE  1  17/100 (17.00%)  29 20/101 (19.80%)  28 18/100 (18.00%)  28
SEDATION  1  7/100 (7.00%)  26 5/101 (4.95%)  18 5/100 (5.00%)  13
SOMNOLENCE  1  6/100 (6.00%)  12 9/101 (8.91%)  16 7/100 (7.00%)  9
Psychiatric disorders       
DISSOCIATION  1  8/100 (8.00%)  37 4/101 (3.96%)  6 4/100 (4.00%)  7
INSOMNIA  1  6/100 (6.00%)  6 5/101 (4.95%)  6 4/100 (4.00%)  4
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Sanjeev Pathak
Organization: AstraZeneca
EMail: ClinicalTrialTransparency@astrazeneca.com
Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01482221     History of Changes
Other Study ID Numbers: D6702C00031
EudraCT number 2011-004690-87
First Submitted: November 28, 2011
First Posted: November 30, 2011
Results First Submitted: October 13, 2014
Results First Posted: April 11, 2017
Last Update Posted: April 11, 2017