Clinical Trial Results:
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
Summary
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EudraCT number |
2011-004690-87 |
Trial protocol |
SK |
Global end of trial date |
09 Oct 2013
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Results information
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Results version number |
v1(current) |
This version publication date |
27 May 2017
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First version publication date |
27 May 2017
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Other versions |
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Summary report(s) |
NS/D6702C00031-CSR Synopsis |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
D6702C00031
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
AstraZeneca
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Sponsor organisation address |
Pepparedsleden 1, Mölndal, Sweden, SE-431 83
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Public contact |
Sanjeev Pathak, AstraZeneca, ClinicalTrialTransparency@astrazeneca.com
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Scientific contact |
Sanjeev Pathak, AstraZeneca, ClinicalTrialTransparency@astrazeneca.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
09 Oct 2013
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
26 Aug 2013
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Global end of trial reached? |
Yes
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Global end of trial date |
09 Oct 2013
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the efficacy of AZD6765 (50 mg or 100 mg/infusion) as adjunct to current antidepressant medication versus antidepressant medication + placebo as assessed by the change from baseline to Week 6 in the MADRS total score in patients with MDD (DSM IV TR 296.2x or 296.3x) who exhibited an inadequate response to 3 or more different antidepressant treatments by history. Inadequate response was defined as persistent symptoms that, as judged by the investigator, continue to meet the diagnostic criteria for a Major Depressive Episode (MDE) according to the DSM IV TR.
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Protection of trial subjects |
Treated in routine care.
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Background therapy |
At least 1 antidepressant medication for a minimum of 6 weeks prior to randomization. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
16 Dec 2011
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Chile: 20
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Country: Number of subjects enrolled |
Slovakia: 27
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Country: Number of subjects enrolled |
South Africa: 17
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Country: Number of subjects enrolled |
United States: 238
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Worldwide total number of subjects |
302
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EEA total number of subjects |
27
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
287
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From 65 to 84 years |
15
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85 years and over |
0
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Recruitment
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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
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Screening 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Roles blinded |
Investigator, Monitor, Subject, Carer, Data analyst, Assessor | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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AZD6765 50 mg | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Intravenous infusion | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
AZD6765
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Solution for Infusion, 0.5 mg/mL
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Arm title
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AZD6765 100 mg | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Intravenous infusion | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
AZD6765
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Solution for Infusion, 1.0 mg/mL
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Arm title
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Placebo | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Intravenous infusion | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Solution for Infusion, 0.9% saline
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Baseline characteristics reporting groups
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Reporting group title |
AZD6765 50 mg
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Reporting group description |
Intravenous infusion | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
AZD6765 100 mg
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Reporting group description |
Intravenous infusion | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Intravenous infusion | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
AZD6765 50 mg
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Reporting group description |
Intravenous infusion | ||
Reporting group title |
AZD6765 100 mg
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Reporting group description |
Intravenous infusion | ||
Reporting group title |
Placebo
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Reporting group description |
Intravenous infusion |
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End point title |
Change from baseline to Week 6 in the Montgomery-Asberg Depression Rating Scale (MADRS) total score | ||||||||||||||||
End point 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.
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End point type |
Primary
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End point timeframe |
Baseline to Week 6
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Statistical analysis title |
Change in MADRS total score - baseline to Week 6 | ||||||||||||||||
Statistical analysis description |
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.
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Comparison groups |
Placebo v AZD6765 50 mg
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Number of subjects included in analysis |
198
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Analysis specification |
Pre-specified
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Analysis type |
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P-value |
= 0.63 [1] | ||||||||||||||||
Method |
Mixed models for repeated measures | ||||||||||||||||
Parameter type |
LS mean difference | ||||||||||||||||
Point estimate |
-1.18
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Confidence interval |
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level |
95% | ||||||||||||||||
sides |
2-sided
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lower limit |
-4.519 | ||||||||||||||||
upper limit |
2.152 | ||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
1.695
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Notes [1] - 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). |
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Statistical analysis title |
Change in MADRS total score - baseline to Week 6 | ||||||||||||||||
Statistical analysis description |
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.
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Comparison groups |
AZD6765 100 mg v Placebo
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Number of subjects included in analysis |
197
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Analysis specification |
Pre-specified
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Analysis type |
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P-value |
= 0.476 [2] | ||||||||||||||||
Method |
Mixed models for repeated measures | ||||||||||||||||
Parameter type |
LS mean difference | ||||||||||||||||
Point estimate |
-1.21
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Confidence interval |
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level |
95% | ||||||||||||||||
sides |
2-sided
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lower limit |
-4.563 | ||||||||||||||||
upper limit |
2.134 | ||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
1.701
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Notes [2] - 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). |
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End point title |
Change from baseline to Week 12 in the Montgomery-Asberg Depression Rating Scale (MADRS) total score | ||||||||||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
Baseline to Week 12
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Statistical analysis title |
Change in MADRS total score - baseline to Week 12 | ||||||||||||||||
Statistical analysis description |
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.
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Comparison groups |
AZD6765 50 mg v Placebo
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Number of subjects included in analysis |
198
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Analysis specification |
Pre-specified
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Analysis type |
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P-value |
= 0.63 [3] | ||||||||||||||||
Method |
Mixed models for repeated measures | ||||||||||||||||
Parameter type |
LS mean difference | ||||||||||||||||
Point estimate |
-2.05
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Confidence interval |
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level |
95% | ||||||||||||||||
sides |
2-sided
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lower limit |
-5.628 | ||||||||||||||||
upper limit |
1.522 | ||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
1.816
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Notes [3] - 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). |
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Statistical analysis title |
Change in MADRS total score - baseline to Week 12 | ||||||||||||||||
Statistical analysis description |
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.
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Comparison groups |
AZD6765 100 mg v Placebo
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Number of subjects included in analysis |
197
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Analysis specification |
Pre-specified
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Analysis type |
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P-value |
= 0.63 [4] | ||||||||||||||||
Method |
Mixed models for repeated measures | ||||||||||||||||
Parameter type |
LS mean difference | ||||||||||||||||
Point estimate |
0.88
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Confidence interval |
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level |
95% | ||||||||||||||||
sides |
2-sided
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lower limit |
-2.72 | ||||||||||||||||
upper limit |
4.485 | ||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
1.83
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Notes [4] - 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). |
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End point 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) | ||||||||||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
Week 6 to Week 12
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Statistical analysis title |
Sustained MADRS Response - Week 6 to Week 12 | ||||||||||||||||
Statistical analysis description |
Logistic regression model including treatment as a fixed effect and the baseline MADRS total score as a covariate.
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Comparison groups |
AZD6765 50 mg v Placebo
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Number of subjects included in analysis |
198
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Analysis specification |
Pre-specified
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Analysis type |
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P-value |
= 0.852 [5] | ||||||||||||||||
Method |
Regression, Logistic | ||||||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||||||
Point estimate |
1.07
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Confidence interval |
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level |
95% | ||||||||||||||||
sides |
2-sided
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lower limit |
0.544 | ||||||||||||||||
upper limit |
2.089 | ||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.366
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Notes [5] - 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). |
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Statistical analysis title |
Sustained MADRS Response - Week 6 to Week 12 | ||||||||||||||||
Statistical analysis description |
Logistic regression model including treatment as a fixed effect and the baseline MADRS total score as a covariate.
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Comparison groups |
AZD6765 100 mg v Placebo
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Number of subjects included in analysis |
197
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Analysis specification |
Pre-specified
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Analysis type |
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P-value |
= 0.821 [6] | ||||||||||||||||
Method |
Regression, Logistic | ||||||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||||||
Point estimate |
1.08
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Confidence interval |
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level |
95% | ||||||||||||||||
sides |
2-sided
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lower limit |
0.552 | ||||||||||||||||
upper limit |
2.115 | ||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.37
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Notes [6] - 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). |
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End point title |
Percentage of patients who were Responders (defined as a ≥50% reduction from baseline in MADRS total score) at Week 6 | ||||||||||||||||
End point description |
The percentage of patients who were Responders (defined as ≥50% reduction from baseline in MADRS total score) was calculated.
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End point type |
Secondary
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End point timeframe |
Baseline to Week 6
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Statistical analysis title |
Adjusted odds ratio of Response at Week 6 | ||||||||||||||||
Statistical analysis description |
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.
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Comparison groups |
AZD6765 50 mg v Placebo
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Number of subjects included in analysis |
168
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Analysis specification |
Pre-specified
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Analysis type |
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P-value |
= 0.751 | ||||||||||||||||
Method |
GEE for repeated measures | ||||||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||||||
Point estimate |
0.9
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Confidence interval |
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level |
95% | ||||||||||||||||
sides |
2-sided
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lower limit |
0.485 | ||||||||||||||||
upper limit |
1.686 | ||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.318
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Statistical analysis title |
Adjusted odds ratio of Response at Week 6 | ||||||||||||||||
Statistical analysis description |
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.
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Comparison groups |
AZD6765 100 mg v Placebo
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Number of subjects included in analysis |
166
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Analysis specification |
Pre-specified
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Analysis type |
|||||||||||||||||
P-value |
= 0.555 | ||||||||||||||||
Method |
GEE for repeated measures | ||||||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||||||
Point estimate |
1.2
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Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.65 | ||||||||||||||||
upper limit |
2.233 | ||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||
Dispersion value |
0.315
|
|
|||||||||||||||||
End point title |
Percentage of patients who were Responders (defined as a ≥50% reduction from baseline in MADRS total score) at Week 12 | ||||||||||||||||
End point description |
The percentage of patients who were Responders (defined as ≥50% reduction from baseline in MADRS total score) was calculated.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline to Week 12
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Adjusted odds ratio of Response at Week 12 | ||||||||||||||||
Statistical analysis description |
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.
|
||||||||||||||||
Comparison groups |
AZD6765 50 mg v Placebo
|
||||||||||||||||
Number of subjects included in analysis |
170
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
|||||||||||||||||
P-value |
= 0.434 | ||||||||||||||||
Method |
GEE for repeated measures | ||||||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||||||
Point estimate |
1.27
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.699 | ||||||||||||||||
upper limit |
2.301 | ||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||
Dispersion value |
0.304
|
||||||||||||||||
Statistical analysis title |
Adjusted odds ratio of Response at Week 12 | ||||||||||||||||
Statistical analysis description |
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.
|
||||||||||||||||
Comparison groups |
AZD6765 100 mg v Placebo
|
||||||||||||||||
Number of subjects included in analysis |
166
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
|||||||||||||||||
P-value |
= 0.286 | ||||||||||||||||
Method |
GEE for repeated measures | ||||||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||||||
Point estimate |
0.71
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.377 | ||||||||||||||||
upper limit |
1.334 | ||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||
Dispersion value |
0.322
|
|
|||||||||||||||||
End point title |
Percentage of patients who were Remitted (defined as MADRS total score ≤10) at Week 6 | ||||||||||||||||
End point description |
The percentage of patients who were Remitted (defined as MADRS total score ≤10) was calculated.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline to Week 6
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Adjusted odds ratio of Remission at Week 6 | ||||||||||||||||
Statistical analysis description |
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.
|
||||||||||||||||
Comparison groups |
AZD6765 50 mg v Placebo
|
||||||||||||||||
Number of subjects included in analysis |
168
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
|||||||||||||||||
P-value |
= 0.357 | ||||||||||||||||
Method |
GEE for repeated measures | ||||||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||||||
Point estimate |
1.42
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.672 | ||||||||||||||||
upper limit |
3.007 | ||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||
Dispersion value |
0.382
|
||||||||||||||||
Statistical analysis title |
Adjusted odds ratio of Remission at Week 6 | ||||||||||||||||
Statistical analysis description |
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.
|
||||||||||||||||
Comparison groups |
AZD6765 100 mg v Placebo
|
||||||||||||||||
Number of subjects included in analysis |
166
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
|||||||||||||||||
P-value |
= 0.463 | ||||||||||||||||
Method |
GEE for repeated measures | ||||||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||||||
Point estimate |
1.33
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.622 | ||||||||||||||||
upper limit |
2.84 | ||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||
Dispersion value |
0.387
|
|
|||||||||||||||||
End point title |
Percentage of patients who were Remitted (defined as MADRS total score ≤10) at Week 12 | ||||||||||||||||
End point description |
The percentage of patients who were Remitted (defined as MADRS total score ≤10) was calculated.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline to Week 12
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Adjusted odds ratio of Remission at Week 12 | ||||||||||||||||
Statistical analysis description |
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.
|
||||||||||||||||
Comparison groups |
AZD6765 50 mg v Placebo
|
||||||||||||||||
Number of subjects included in analysis |
170
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
|||||||||||||||||
P-value |
= 0.911 | ||||||||||||||||
Method |
GEE for repeated measures | ||||||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||||||
Point estimate |
1.04
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.532 | ||||||||||||||||
upper limit |
2.031 | ||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||
Dispersion value |
0.342
|
||||||||||||||||
Statistical analysis title |
Adjusted odds ratio of Remission at Week 12 | ||||||||||||||||
Statistical analysis description |
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.
|
||||||||||||||||
Comparison groups |
AZD6765 100 mg v Placebo
|
||||||||||||||||
Number of subjects included in analysis |
166
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
|||||||||||||||||
P-value |
= 0.509 | ||||||||||||||||
Method |
GEE for repeated measures | ||||||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||||||
Point estimate |
0.78
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.382 | ||||||||||||||||
upper limit |
1.613 | ||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||
Dispersion value |
0.368
|
|
|||||||||||||||||||||||||
End point title |
Change from baseline in functional impairment as measured by the change from baseline in the Sheehan Disability Scale (SDS) total score | ||||||||||||||||||||||||
End point 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).
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Baseline to Week 12
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Statistical analysis title |
Change in SDS total score - baseline to Week 6 | ||||||||||||||||||||||||
Statistical analysis description |
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.
|
||||||||||||||||||||||||
Comparison groups |
AZD6765 50 mg v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
198
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
|||||||||||||||||||||||||
P-value |
= 0.889 [7] | ||||||||||||||||||||||||
Method |
Mixed models for repeated measures | ||||||||||||||||||||||||
Parameter type |
LS mean difference | ||||||||||||||||||||||||
Point estimate |
-0.17
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-2.609 | ||||||||||||||||||||||||
upper limit |
2.264 | ||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||||||||
Dispersion value |
1.238
|
||||||||||||||||||||||||
Notes [7] - Analysis for change in SDS total score from baseline to Week 6 |
|||||||||||||||||||||||||
Statistical analysis title |
Change in SDS total score - baseline to Week 6 | ||||||||||||||||||||||||
Statistical analysis description |
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.
|
||||||||||||||||||||||||
Comparison groups |
AZD6765 100 mg v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
197
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
|||||||||||||||||||||||||
P-value |
= 0.992 [8] | ||||||||||||||||||||||||
Method |
Mixed models for repeated measures | ||||||||||||||||||||||||
Parameter type |
LS mean difference | ||||||||||||||||||||||||
Point estimate |
0.01
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-2.477 | ||||||||||||||||||||||||
upper limit |
2.501 | ||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||||||||
Dispersion value |
1.264
|
||||||||||||||||||||||||
Notes [8] - Analysis for change in SDS total score from baseline to Week 6 |
|||||||||||||||||||||||||
Statistical analysis title |
Change in SDS total score - baseline to Week 12 | ||||||||||||||||||||||||
Statistical analysis description |
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.
|
||||||||||||||||||||||||
Comparison groups |
AZD6765 50 mg v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
198
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
|||||||||||||||||||||||||
P-value |
= 0.392 [9] | ||||||||||||||||||||||||
Method |
Mixed models for repeated measures | ||||||||||||||||||||||||
Parameter type |
LS mean difference | ||||||||||||||||||||||||
Point estimate |
1.11
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-1.448 | ||||||||||||||||||||||||
upper limit |
3.678 | ||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||||||||
Dispersion value |
1.301
|
||||||||||||||||||||||||
Notes [9] - Analysis for change in SDS total score from baseline to Week 12 |
|||||||||||||||||||||||||
Statistical analysis title |
Change in SDS total score - baseline to Week 12 | ||||||||||||||||||||||||
Statistical analysis description |
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.
|
||||||||||||||||||||||||
Comparison groups |
AZD6765 100 mg v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
197
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
|||||||||||||||||||||||||
P-value |
= 0.333 [10] | ||||||||||||||||||||||||
Method |
Mixed models for repeated measures | ||||||||||||||||||||||||
Parameter type |
LS mean difference | ||||||||||||||||||||||||
Point estimate |
1.29
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-1.327 | ||||||||||||||||||||||||
upper limit |
3.908 | ||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||||||||
Dispersion value |
1.329
|
||||||||||||||||||||||||
Notes [10] - Analysis for changed in SDS total score from baseline to Week 12 |
|
|||||||||||||||||||||||||
End point title |
Change in severity of depressive symptoms as measured by change from baseline in the Clinical Global Impression-Severity (CGI-S) score | ||||||||||||||||||||||||
End point description |
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).
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Baseline to Week 12
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Statistical analysis title |
Change in CGI-S score - baseline to Week 6 | ||||||||||||||||||||||||
Statistical analysis description |
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.
|
||||||||||||||||||||||||
Comparison groups |
AZD6765 50 mg v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
198
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
|||||||||||||||||||||||||
P-value |
= 0.728 [11] | ||||||||||||||||||||||||
Method |
Mixed models for repeated measures | ||||||||||||||||||||||||
Parameter type |
LS mean difference | ||||||||||||||||||||||||
Point estimate |
-0.1
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-0.49 | ||||||||||||||||||||||||
upper limit |
0.34 | ||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||||||||
Dispersion value |
0.21
|
||||||||||||||||||||||||
Notes [11] - Analysis for change in CGI-S total score from baseline to Week 6 |
|||||||||||||||||||||||||
Statistical analysis title |
Change in CGI-S score - baseline to Week 6 | ||||||||||||||||||||||||
Statistical analysis description |
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.
|
||||||||||||||||||||||||
Comparison groups |
AZD6765 100 mg v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
197
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
|||||||||||||||||||||||||
P-value |
= 0.562 [12] | ||||||||||||||||||||||||
Method |
Mixed models for repeated measures | ||||||||||||||||||||||||
Parameter type |
LS mean difference | ||||||||||||||||||||||||
Point estimate |
-0.1
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-0.54 | ||||||||||||||||||||||||
upper limit |
0.29 | ||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||||||||
Dispersion value |
0.21
|
||||||||||||||||||||||||
Notes [12] - Analysis for change in CGI-S total score from baseline to Week 6 |
|||||||||||||||||||||||||
Statistical analysis title |
Change in CGI-S score - baseline to Week 12 | ||||||||||||||||||||||||
Statistical analysis description |
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.
|
||||||||||||||||||||||||
Comparison groups |
AZD6765 50 mg v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
198
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
|||||||||||||||||||||||||
P-value |
= 0.283 [13] | ||||||||||||||||||||||||
Method |
Mixed models for repeated measures | ||||||||||||||||||||||||
Parameter type |
LS mean difference | ||||||||||||||||||||||||
Point estimate |
-0.2
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-0.64 | ||||||||||||||||||||||||
upper limit |
0.19 | ||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||||||||
Dispersion value |
0.21
|
||||||||||||||||||||||||
Notes [13] - Analysis for change in CGI-S total score from baseline to Week 12 |
|||||||||||||||||||||||||
Statistical analysis title |
Change in CGI-S score - baseline to Week 12 | ||||||||||||||||||||||||
Statistical analysis description |
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.
|
||||||||||||||||||||||||
Comparison groups |
AZD6765 100 mg v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
197
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
|||||||||||||||||||||||||
P-value |
= 0.54 [14] | ||||||||||||||||||||||||
Method |
Mixed models for repeated measures | ||||||||||||||||||||||||
Parameter type |
LS mean difference | ||||||||||||||||||||||||
Point estimate |
0.1
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-0.29 | ||||||||||||||||||||||||
upper limit |
0.55 | ||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||||||||
Dispersion value |
0.21
|
||||||||||||||||||||||||
Notes [14] - Analysis for changed in CGI-S total score from baseline to Week 12 |
|
|||||||||||||||||
End point 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 | ||||||||||||||||
End point 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.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline to Week 6
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Response in CGI-I - baseline to Week 6 | ||||||||||||||||
Statistical analysis description |
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.
|
||||||||||||||||
Comparison groups |
AZD6765 50 mg v Placebo
|
||||||||||||||||
Number of subjects included in analysis |
168
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
|||||||||||||||||
P-value |
= 0.067 | ||||||||||||||||
Method |
GEE for repeated measures | ||||||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||||||
Point estimate |
1.74
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.962 | ||||||||||||||||
upper limit |
3.141 | ||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||
Dispersion value |
0.302
|
||||||||||||||||
Statistical analysis title |
Response in CGI-I - baseline to Week 6 | ||||||||||||||||
Statistical analysis description |
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.
|
||||||||||||||||
Comparison groups |
AZD6765 100 mg v Placebo
|
||||||||||||||||
Number of subjects included in analysis |
166
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
|||||||||||||||||
P-value |
= 0.23 | ||||||||||||||||
Method |
GEE for repeated measures | ||||||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||||||
Point estimate |
1.43
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.798 | ||||||||||||||||
upper limit |
2.558 | ||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||
Dispersion value |
0.297
|
|
|||||||||||||||||
End point 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 | ||||||||||||||||
End point 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.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline to Week 12
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Response in CGI-I - baseline to Week 12 | ||||||||||||||||
Statistical analysis description |
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.
|
||||||||||||||||
Comparison groups |
AZD6765 50 mg v Placebo
|
||||||||||||||||
Number of subjects included in analysis |
170
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
|||||||||||||||||
P-value |
= 0.268 | ||||||||||||||||
Method |
GEE for repeated measures | ||||||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||||||
Point estimate |
1.38
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.78 | ||||||||||||||||
upper limit |
2.447 | ||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||
Dispersion value |
0.292
|
||||||||||||||||
Statistical analysis title |
Response in CGI-I - baseline to Week 12 | ||||||||||||||||
Statistical analysis description |
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.
|
||||||||||||||||
Comparison groups |
AZD6765 100 mg v Placebo
|
||||||||||||||||
Number of subjects included in analysis |
166
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
|||||||||||||||||
P-value |
= 0.909 | ||||||||||||||||
Method |
GEE for repeated measures | ||||||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||||||
Point estimate |
0.97
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.533 | ||||||||||||||||
upper limit |
1.75 | ||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||
Dispersion value |
0.303
|
|
|||||||||||||||||||||||||
End point 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 | ||||||||||||||||||||||||
End point 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).
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Baseline to Week 12
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Statistical analysis title |
Change in QIDS-SR-16 score - baseline to Week 6 | ||||||||||||||||||||||||
Statistical analysis description |
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.
|
||||||||||||||||||||||||
Comparison groups |
AZD6765 50 mg v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
198
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
|||||||||||||||||||||||||
P-value |
= 0.505 [15] | ||||||||||||||||||||||||
Method |
Mixed models for repeated measures | ||||||||||||||||||||||||
Parameter type |
LS mean difference | ||||||||||||||||||||||||
Point estimate |
-0.6
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-2.29 | ||||||||||||||||||||||||
upper limit |
1.13 | ||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||||||||
Dispersion value |
0.87
|
||||||||||||||||||||||||
Notes [15] - Analysis for change in QIDS-SR-16 total score from baseline to Week 6 |
|||||||||||||||||||||||||
Statistical analysis title |
Change in QIDS-SR-16 score - baseline to Week 6 | ||||||||||||||||||||||||
Statistical analysis description |
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.
|
||||||||||||||||||||||||
Comparison groups |
AZD6765 100 mg v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
197
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
|||||||||||||||||||||||||
P-value |
= 0.842 [16] | ||||||||||||||||||||||||
Method |
Mixed models for repeated measures | ||||||||||||||||||||||||
Parameter type |
LS mean difference | ||||||||||||||||||||||||
Point estimate |
0.2
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-1.56 | ||||||||||||||||||||||||
upper limit |
1.91 | ||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||||||||
Dispersion value |
0.88
|
||||||||||||||||||||||||
Notes [16] - Analysis for change in QIDS-SR-16 total score from baseline to Week 6 |
|||||||||||||||||||||||||
Statistical analysis title |
Change in QIDS-SR-16 score - baseline to Week 12 | ||||||||||||||||||||||||
Statistical analysis description |
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.
|
||||||||||||||||||||||||
Comparison groups |
AZD6765 50 mg v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
198
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
|||||||||||||||||||||||||
P-value |
= 0.788 [17] | ||||||||||||||||||||||||
Method |
Mixed models for repeated measures | ||||||||||||||||||||||||
Parameter type |
LS mean difference | ||||||||||||||||||||||||
Point estimate |
-0.2
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-1.98 | ||||||||||||||||||||||||
upper limit |
1.51 | ||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||||||||
Dispersion value |
0.89
|
||||||||||||||||||||||||
Notes [17] - Analysis for change in QIDS-SR-16 total score from baseline to Week 12 |
|||||||||||||||||||||||||
Statistical analysis title |
Change in QIDS-SR-16 score - baseline to Week 12 | ||||||||||||||||||||||||
Statistical analysis description |
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.
|
||||||||||||||||||||||||
Comparison groups |
AZD6765 100 mg v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
197
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
|||||||||||||||||||||||||
P-value |
= 0.133 [18] | ||||||||||||||||||||||||
Method |
Mixed models for repeated measures | ||||||||||||||||||||||||
Parameter type |
LS mean difference | ||||||||||||||||||||||||
Point estimate |
1.4
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-0.42 | ||||||||||||||||||||||||
upper limit |
3.12 | ||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||||||||
Dispersion value |
0.9
|
||||||||||||||||||||||||
Notes [18] - Analysis for changed in QIDS-SR-16 total score from baseline to Week 12 |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Adverse events were collected from the time of signature of informed consent throughout the treatment period and follow-up period.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional 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.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
16.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
AZD6765iv 100 mg
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Intravenous infusion | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
AZD6765iv 50 mg
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Intravenous infusion | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Intravenous infusion | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
16 Feb 2012 |
Clarifications regarding timing of assessments, strengthening of requirements for contraception to also include male patients and male partners, addition of a new exclusion criterion for patients who during the past 2 years have met DSM IV-R-TR diagnostic criteria for post-traumatic stress disorder, addition of ethanol and methaqualone to exclusion criterion #8, modification of exclusion criterion #12 to exclude patients with a C-SSRS evaluation of type 4 or 5 within the last 6 months of screening or randomization, deletion of sub-criterion regarding insulin use in exclusion criterion #15, addition of laboratory values that signify a major medical illness that is inadequately controlled to exclusion criterion #18, exclusion criterion # 21 was revised to not limit the exclusions to hospitalizations for MDD only, addition of an exclusion criterion (#22) to clarify that a failed SAFER interview excludes a patient from participating in the study. |
||
25 Oct 2012 |
Increase in the number of study sites, clarification that, to be eligible for the study, patients’ lifetime history of inadequate response to 3 or more antidepressant treatments must include the current antidepressant medication, exclusion criterion #11 was revised to allow for repeat testing, addition of a new exclusion criterion to exclude patients with a current diagnosis of sleep apnea, addition of a new exclusion criterion to exclude patients with a BMI ≥45 kg/m2, removal of the SAFER interview, removal of the 8-week observation period, addition of a 14-day follow-up visit. |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |