Major Depressive Disorder
Conditions
Keywords
Major Depressive Disorder, MDD, Inadequate Response to Antidepressant Therapy, Channel blocker of the NMDA class of glutamate receptors
Brief summary
The purpose of this study is to assess the effect and safety of AZD6765 in patients with major depressive disorder who exhibit inadequate response to antidepressants. AZD6765 is a channel blocker of the N-methyl-D-aspartate (NMDA) class of glutamate receptors.
Detailed description
A Multicenter, Randomized, Double-blind, Parallel Group, Placebo-controlled, Phase IIb Efficacy and Safety Study of Adjunctive AZD6765 in Patients with Major Depressive Disorder (MDD) and a History of Inadequate Response to Antidepressants
Interventions
DRUGAZD6765 iv
50 mg (AZD6765 Solution for Infusion, 0.5 mg/mL) by iv infusion.
DRUGPlacebo
0.9 sodium chloride \[normal saline\] solution for injection by iv infusion
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Provision of signed and dated informed consent before initiation of any study-related procedures. * Male or female patients aged 18 to 70 years, inclusive. * The patient must have a clinical diagnosis of major depressive disorder with a lifetime history of inadequate response to at least 3 antidepressants. * Women of child-bearing potential must have a negative serum pregnancy test and confirmed use of a highly effective form of birth control before enrollment for a minimum of 3 months before study start. * Outpatient status at screening and randomization visits.
Exclusion criteria
* Patients with a history of diagnosed bipolar disorder or schizophrenia or schizoaffective disorder or currently exhibiting psychotic features associated with their depression; dementia or suspicion thereof. * Patients who have had a suicide attempt within the last 6 months. * Electroconvulsive therapy (ECT), vagal nerve stimulation (VNS) or transcranial magnetic stimulation (TMS) or previous treatment with ketamine infusion within the 6 months prior to screening, or any history of deep brain stimulation. * Patients with any history of seizure disorder (except for febrile seizures in childhood). * Pregnancy or lactation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 6 in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Baseline to Week 6 | A 10-item scale for the evaluation of depressive symptoms. Each MADRS item is rated on a 0 to 6 scale. The MADRS total score is calculated as the sum of the 10 individual item scores; the total score can range from 0 to 60. Higher MADRS scores indicate higher levels of depressive symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Sustained Response From Week 6 to Week 12 (Defined as ≥50% Reduction From Baseline in the MADRS Total Score at Week 6 and Which is Maintained Through Week 12) | Week 6 to Week 12 | The percentage of patients with with Sustained Response (defined as ≥50% reduction from baseline in the MADRS total score at Week 6 and which is maintained through Week 12) was calculated. |
| Percentage of Patients Who Were Responders (Defined as a ≥50% Reduction From Baseline in MADRS Total Score) at Week 6 | Baseline to Week 6 | The percentage of patients who were Responders (defined as ≥50% reduction from baseline in MADRS total score) was calculated. |
| Percentage of Patients Who Were Responders (Defined as a ≥50% Reduction From Baseline in MADRS Total Score) at Week 12 | Baseline to Week 12 | The percentage of patients who were Responders (defined as ≥50% reduction from baseline in MADRS total score) was calculated. |
| Percentage of Patients Who Were Remitted (Defined as MADRS Total Score ≤10) at Week 6 | Baseline to Week 6 | The percentage of patients who were Remitted (defined as MADRS total score ≤10) was calculated. |
| Percentage of Patients Who Were Remitted (Defined as MADRS Total Score ≤10) at Week 12 | Baseline to Week 12 | The percentage of patients who were Remitted (defined as MADRS total score ≤10) was calculated. |
| Change From Baseline to Week 12 in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Baseline to Week 12 | A 10-item scale for the evaluation of depressive symptoms. Each MADRS item is rated on a 0 to 6 scale. The MADRS total score is calculated as the sum of the 10 individual item scores; the total score can range from 0 to 60. Higher MADRS scores indicate higher levels of depressive symptoms. |
| Change in Severity of Depressive Symptoms as Measured by Change From Baseline in the Clinical Global Impression-Severity (CGI-S) Score | Baseline to Week 12 | Clinical Global Impression - Severity (CGI-S) scale rates the severity of the patient's illness at the time of assessment, range from 1 (normal, not ill) to 7 (very severely ill). |
| Change in Severity of Depressive Symptoms as Measured by the CGI-I Response (Defined as CGI-I Rating of Very Much Improved or Much Improved) at Week 6 | Baseline to Week 6 | A 3-part, clinician-administered scale that rates the improvement or worsening of the patient's illness from randomization (baseline). Each item is scored on a 1 to 7 scale. CGI-I scores \>4 indicate worsening, while scores \<4 indicate improvement. |
| Change in Severity of Depressive Symptoms as Measured by the CGI-I Response (Defined as CGI-I Rating of Very Much Improved or Much Improved) at Week 12 | Baseline to Week 12 | A 3-part, clinician-administered scale that rates the improvement or worsening of the patient's illness from randomization (baseline). Each item is scored on a 1 to 7 scale. CGI-I scores \>4 indicate worsening, while scores \<4 indicate improvement. |
| Change From Baseline in Self-rated Severity of Depressive Symptoms as Measured by Quick Inventory of Depressive Symptomatology Self-Rated 16-item Scale (QIDS-SR-16) Total Score | Baseline to Week 12 | A 16-question self-report inventory that includes the 9 Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) criteria symptom domains: sad mood, concentration, self-outlook, suicidal ideation, involvement, energy/fatigability, sleep disturbance (4 items: initial, middle, late insomnia, and hypersomnia), appetite/weight increased or decrease (4 items), and psychomotor agitation/retardation (2 items). The QIDS-SR-16 total scores range from 0 (least severe) to 27 (most severe). |
| Change From Baseline in Functional Impairment as Measured by the Change From Baseline in the Sheehan Disability Scale (SDS) Total Score | Baseline to Week 12 | A 3-item, self-administered scale that measures the extent a patient is impaired by their disease. Higher scores indicate more severe impairment. The SDS total score is calculated as the sum of the score for the 3 intercorrelated domains (school/work, social life, and family life/home responsibilities), ranges from 0 (no impairment) to 30 (most severe impairment). |
Countries
Chile, Slovakia, South Africa, United States
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| AZD6765 50 mg Intravenous infusion | 101 |
| AZD6765 100 mg Intravenous infusion | 101 |
| Placebo Intravenous infusion | 100 |
| Total | 302 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 7 | 3 |
| Overall Study | Condition under Investigation Worsened | 3 | 2 | 4 |
| Overall Study | Incorrect randomization | 0 | 1 | 0 |
| Overall Study | Lack of Efficacy | 1 | 0 | 1 |
| Overall Study | Lost to Follow-up | 3 | 2 | 1 |
| Overall Study | Physician Decision | 0 | 1 | 0 |
| Overall Study | Severe Non-Compliance to Protocol | 1 | 0 | 1 |
| Overall Study | Study-Specific Withdrawal Criteria | 2 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 10 | 7 | 12 |
Baseline characteristics
| Characteristic | AZD6765 50 mg | AZD6765 100 mg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 47.7 Years STANDARD_DEVIATION 11.19 | 47.5 Years STANDARD_DEVIATION 11.89 | 49.5 Years STANDARD_DEVIATION 11.12 | 48.2 Years STANDARD_DEVIATION 11.4 |
| Race/Ethnicity, Customized Asian | 0 Participants | 3 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Black or African American | 8 Participants | 11 Participants | 6 Participants | 25 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 0 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized White | 91 Participants | 87 Participants | 91 Participants | 269 Participants |
| Sex: Female, Male Female | 62 Participants | 70 Participants | 65 Participants | 197 Participants |
| Sex: Female, Male Male | 39 Participants | 31 Participants | 35 Participants | 105 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 68 / 100 | 59 / 101 | 47 / 100 |
| serious Total, serious adverse events | 4 / 100 | 2 / 101 | 4 / 100 |
Outcome results
Primary
Change From Baseline to Week 6 in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
A 10-item scale for the evaluation of depressive symptoms. Each MADRS item is rated on a 0 to 6 scale. The MADRS total score is calculated as the sum of the 10 individual item scores; the total score can range from 0 to 60. Higher MADRS scores indicate higher levels of depressive symptoms.
Time frame: Baseline to Week 6
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AZD6765 50 mg | Change From Baseline to Week 6 in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | -14.37 units on a scale | Standard Error 1.238 |
| AZD6765 100 mg | Change From Baseline to Week 6 in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | -14.40 units on a scale | Standard Error 1.244 |
| Placebo | Change From Baseline to Week 6 in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | -13.18 units on a scale | Standard Error 1.266 |
Comparison: 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.p-value: 0.6395% CI: [-4.519, 2.152]Mixed models for repeated measures
Comparison: 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.p-value: 0.47695% CI: [-4.563, 2.134]Mixed models for repeated measures
Secondary
Change From Baseline in Functional Impairment as Measured by the Change From Baseline in the Sheehan Disability Scale (SDS) Total Score
A 3-item, self-administered scale that measures the extent a patient is impaired by their disease. Higher scores indicate more severe impairment. The SDS total score is calculated as the sum of the score for the 3 intercorrelated domains (school/work, social life, and family life/home responsibilities), ranges from 0 (no impairment) to 30 (most severe impairment).
Time frame: Baseline to Week 12
Population: 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 | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| AZD6765 50 mg | Change From Baseline in Functional Impairment as Measured by the Change From Baseline in the Sheehan Disability Scale (SDS) Total Score | Week 6 | -7.08 units on a scale | Standard Error 0.959 |
| AZD6765 50 mg | Change From Baseline in Functional Impairment as Measured by the Change From Baseline in the Sheehan Disability Scale (SDS) Total Score | Week 12 | -6.98 units on a scale | Standard Error 0.995 |
| AZD6765 100 mg | Change From Baseline in Functional Impairment as Measured by the Change From Baseline in the Sheehan Disability Scale (SDS) Total Score | Week 6 | -6.90 units on a scale | Standard Error 0.981 |
| AZD6765 100 mg | Change From Baseline in Functional Impairment as Measured by the Change From Baseline in the Sheehan Disability Scale (SDS) Total Score | Week 12 | -6.80 units on a scale | Standard Error 1.021 |
| Placebo | Change From Baseline in Functional Impairment as Measured by the Change From Baseline in the Sheehan Disability Scale (SDS) Total Score | Week 6 | -6.91 units on a scale | Standard Error 0.989 |
| Placebo | Change From Baseline in Functional Impairment as Measured by the Change From Baseline in the Sheehan Disability Scale (SDS) Total Score | Week 12 | -8.09 units on a scale | Standard Error 1.034 |
Comparison: 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.p-value: 0.88995% CI: [-2.609, 2.264]Mixed models for repeated measures
Comparison: 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.p-value: 0.99295% CI: [-2.477, 2.501]Mixed models for repeated measures
Comparison: 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.p-value: 0.39295% CI: [-1.448, 3.678]Mixed models for repeated measures
Comparison: 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.p-value: 0.33395% CI: [-1.327, 3.908]Mixed models for repeated measures
Secondary
Change From Baseline in Self-rated Severity of Depressive Symptoms as Measured by Quick Inventory of Depressive Symptomatology Self-Rated 16-item Scale (QIDS-SR-16) Total Score
A 16-question self-report inventory that includes the 9 Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) criteria symptom domains: sad mood, concentration, self-outlook, suicidal ideation, involvement, energy/fatigability, sleep disturbance (4 items: initial, middle, late insomnia, and hypersomnia), appetite/weight increased or decrease (4 items), and psychomotor agitation/retardation (2 items). The QIDS-SR-16 total scores range from 0 (least severe) to 27 (most severe).
Time frame: Baseline to Week 12
Population: 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 | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| AZD6765 50 mg | 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 | Week 6 | -8.7 units on a scale | Standard Error 0.69 |
| AZD6765 50 mg | 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 | Week 12 | -9.2 units on a scale | Standard Error 0.7 |
| AZD6765 100 mg | 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 | Week 6 | -7.9 units on a scale | Standard Error 0.7 |
| AZD6765 100 mg | 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 | Week 12 | -7.6 units on a scale | Standard Error 0.71 |
| Placebo | 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 | Week 6 | -8.1 units on a scale | Standard Error 0.71 |
| Placebo | 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 | Week 12 | -8.9 units on a scale | Standard Error 0.72 |
Comparison: 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.p-value: 0.50595% CI: [-2.29, 1.13]Mixed models for repeated measures
Comparison: 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.p-value: 0.84295% CI: [-1.56, 1.91]Mixed models for repeated measures
Comparison: 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.p-value: 0.78895% CI: [-1.98, 1.51]Mixed models for repeated measures
Comparison: 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.p-value: 0.13395% CI: [-0.42, 3.12]Mixed models for repeated measures
Secondary
Change From Baseline to Week 12 in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
A 10-item scale for the evaluation of depressive symptoms. Each MADRS item is rated on a 0 to 6 scale. The MADRS total score is calculated as the sum of the 10 individual item scores; the total score can range from 0 to 60. Higher MADRS scores indicate higher levels of depressive symptoms.
Time frame: Baseline to Week 12
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AZD6765 50 mg | Change From Baseline to Week 12 in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | -15.97 units on a scale | Standard Error 1.313 |
| AZD6765 100 mg | Change From Baseline to Week 12 in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | -13.03 units on a scale | Standard Error 1.332 |
| Placebo | Change From Baseline to Week 12 in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | -13.92 units on a scale | Standard Error 1.354 |
Comparison: 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.p-value: 0.6395% CI: [-5.628, 1.522]Mixed models for repeated measures
Comparison: 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.p-value: 0.6395% CI: [-2.72, 4.485]Mixed models for repeated measures
Secondary
Change in Severity of Depressive Symptoms as Measured by Change From Baseline in the Clinical Global Impression-Severity (CGI-S) Score
Clinical Global Impression - Severity (CGI-S) scale rates the severity of the patient's illness at the time of assessment, range from 1 (normal, not ill) to 7 (very severely ill).
Time frame: Baseline to Week 12
Population: 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 | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| AZD6765 50 mg | Change in Severity of Depressive Symptoms as Measured by Change From Baseline in the Clinical Global Impression-Severity (CGI-S) Score | Week 6 | -1.5 units on a scale | Standard Error 0.16 |
| AZD6765 50 mg | Change in Severity of Depressive Symptoms as Measured by Change From Baseline in the Clinical Global Impression-Severity (CGI-S) Score | Week 12 | -1.8 units on a scale | Standard Error 0.16 |
| AZD6765 100 mg | Change in Severity of Depressive Symptoms as Measured by Change From Baseline in the Clinical Global Impression-Severity (CGI-S) Score | Week 12 | -1.5 units on a scale | Standard Error 0.16 |
| AZD6765 100 mg | Change in Severity of Depressive Symptoms as Measured by Change From Baseline in the Clinical Global Impression-Severity (CGI-S) Score | Week 6 | -1.5 units on a scale | Standard Error 0.16 |
| Placebo | Change in Severity of Depressive Symptoms as Measured by Change From Baseline in the Clinical Global Impression-Severity (CGI-S) Score | Week 6 | -1.4 units on a scale | Standard Error 0.16 |
| Placebo | Change in Severity of Depressive Symptoms as Measured by Change From Baseline in the Clinical Global Impression-Severity (CGI-S) Score | Week 12 | -1.6 units on a scale | Standard Error 0.16 |
Comparison: 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.p-value: 0.72895% CI: [-0.49, 0.34]Mixed models for repeated measures
Comparison: 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.p-value: 0.56295% CI: [-0.54, 0.29]Mixed models for repeated measures
Comparison: 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.p-value: 0.28395% CI: [-0.64, 0.19]Mixed models for repeated measures
Comparison: 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.p-value: 0.5495% CI: [-0.29, 0.55]Mixed models for repeated measures
Secondary
Change in Severity of Depressive Symptoms as Measured by the CGI-I Response (Defined as CGI-I Rating of Very Much Improved or Much Improved) at Week 12
A 3-part, clinician-administered scale that rates the improvement or worsening of the patient's illness from randomization (baseline). Each item is scored on a 1 to 7 scale. CGI-I scores \>4 indicate worsening, while scores \<4 indicate improvement.
Time frame: Baseline to Week 12
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| AZD6765 50 mg | 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 | 50.6 percentage of participants analyzed |
| AZD6765 100 mg | 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 | 44.7 percentage of participants analyzed |
| Placebo | 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 | 40.7 percentage of participants analyzed |
Comparison: 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.p-value: 0.26895% CI: [0.78, 2.447]GEE for repeated measures
Comparison: 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.p-value: 0.90995% CI: [0.533, 1.75]GEE for repeated measures
Secondary
Change in Severity of Depressive Symptoms as Measured by the CGI-I Response (Defined as CGI-I Rating of Very Much Improved or Much Improved) at Week 6
A 3-part, clinician-administered scale that rates the improvement or worsening of the patient's illness from randomization (baseline). Each item is scored on a 1 to 7 scale. CGI-I scores \>4 indicate worsening, while scores \<4 indicate improvement.
Time frame: Baseline to Week 6
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| AZD6765 50 mg | 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 | 51.2 percentage of participants analyzed |
| AZD6765 100 mg | 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 | 47.6 percentage of participants analyzed |
| Placebo | 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 | 37.8 percentage of participants analyzed |
Comparison: 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.p-value: 0.06795% CI: [0.962, 3.141]GEE for repeated measures
Comparison: 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.p-value: 0.2395% CI: [0.798, 2.558]GEE for repeated measures
Secondary
Percentage of Patients Who Were Remitted (Defined as MADRS Total Score ≤10) at Week 12
The percentage of patients who were Remitted (defined as MADRS total score ≤10) was calculated.
Time frame: Baseline to Week 12
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| AZD6765 50 mg | Percentage of Patients Who Were Remitted (Defined as MADRS Total Score ≤10) at Week 12 | 27.0 percentage of participants analyzed |
| AZD6765 100 mg | Percentage of Patients Who Were Remitted (Defined as MADRS Total Score ≤10) at Week 12 | 22.4 percentage of participants analyzed |
| Placebo | Percentage of Patients Who Were Remitted (Defined as MADRS Total Score ≤10) at Week 12 | 25.9 percentage of participants analyzed |
Comparison: 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.p-value: 0.91195% CI: [0.532, 2.031]GEE for repeated measures
Comparison: 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.p-value: 0.50995% CI: [0.382, 1.613]GEE for repeated measures
Secondary
Percentage of Patients Who Were Remitted (Defined as MADRS Total Score ≤10) at Week 6
The percentage of patients who were Remitted (defined as MADRS total score ≤10) was calculated.
Time frame: Baseline to Week 6
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| AZD6765 50 mg | Percentage of Patients Who Were Remitted (Defined as MADRS Total Score ≤10) at Week 6 | 23.3 percentage of participants analyzed |
| AZD6765 100 mg | Percentage of Patients Who Were Remitted (Defined as MADRS Total Score ≤10) at Week 6 | 23.8 percentage of participants analyzed |
| Placebo | Percentage of Patients Who Were Remitted (Defined as MADRS Total Score ≤10) at Week 6 | 18.3 percentage of participants analyzed |
Comparison: 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.p-value: 0.35795% CI: [0.672, 3.007]GEE for repeated measures
Comparison: 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.p-value: 0.46395% CI: [0.622, 2.84]GEE for repeated measures
Secondary
Percentage of Patients Who Were Responders (Defined as a ≥50% Reduction From Baseline in MADRS Total Score) at Week 12
The percentage of patients who were Responders (defined as ≥50% reduction from baseline in MADRS total score) was calculated.
Time frame: Baseline to Week 12
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| AZD6765 50 mg | Percentage of Patients Who Were Responders (Defined as a ≥50% Reduction From Baseline in MADRS Total Score) at Week 12 | 48.3 percentage of participants analyzed |
| AZD6765 100 mg | Percentage of Patients Who Were Responders (Defined as a ≥50% Reduction From Baseline in MADRS Total Score) at Week 12 | 36.5 percentage of participants analyzed |
| Placebo | Percentage of Patients Who Were Responders (Defined as a ≥50% Reduction From Baseline in MADRS Total Score) at Week 12 | 40.7 percentage of participants analyzed |
Comparison: 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.p-value: 0.43495% CI: [0.699, 2.301]GEE for repeated measures
Comparison: 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.p-value: 0.28695% CI: [0.377, 1.334]GEE for repeated measures
Secondary
Percentage of Patients Who Were Responders (Defined as a ≥50% Reduction From Baseline in MADRS Total Score) at Week 6
The percentage of patients who were Responders (defined as ≥50% reduction from baseline in MADRS total score) was calculated.
Time frame: Baseline to Week 6
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| AZD6765 50 mg | Percentage of Patients Who Were Responders (Defined as a ≥50% Reduction From Baseline in MADRS Total Score) at Week 6 | 36.0 percentage of participants analyzed |
| AZD6765 100 mg | Percentage of Patients Who Were Responders (Defined as a ≥50% Reduction From Baseline in MADRS Total Score) at Week 6 | 44.0 percentage of participants analyzed |
| Placebo | Percentage of Patients Who Were Responders (Defined as a ≥50% Reduction From Baseline in MADRS Total Score) at Week 6 | 39.0 percentage of participants analyzed |
Comparison: 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.p-value: 0.75195% CI: [0.485, 1.686]GEE for repeated measures
Comparison: 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.p-value: 0.55595% CI: [0.65, 2.233]GEE for repeated measures
Secondary
Percentage of Patients With Sustained Response From Week 6 to Week 12 (Defined as ≥50% Reduction From Baseline in the MADRS Total Score at Week 6 and Which is Maintained Through Week 12)
The percentage of patients with with Sustained Response (defined as ≥50% reduction from baseline in the MADRS total score at Week 6 and which is maintained through Week 12) was calculated.
Time frame: Week 6 to Week 12
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| AZD6765 50 mg | 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) | 22.8 percentage of participants analyzed |
| AZD6765 100 mg | 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) | 23.0 percentage of participants analyzed |
| Placebo | 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) | 21.6 percentage of participants analyzed |
Comparison: Logistic regression model including treatment as a fixed effect and the baseline MADRS total score as a covariate.p-value: 0.85295% CI: [0.544, 2.089]Regression, Logistic
Comparison: Logistic regression model including treatment as a fixed effect and the baseline MADRS total score as a covariate.p-value: 0.82195% CI: [0.552, 2.115]Regression, Logistic