Major Depressive Disorder
Conditions
Keywords
Depression
Brief summary
The purpose of this study is to prove the principle that treatment with AZD7268 reduces depressive symptoms in patients with Major Depressive Disorder (MDD) compared with placebo.
Interventions
DRUGAZD7268
15 mg, oral, twice daily (BID)
DRUGEscitalopram
20 mg, oral, once daily (QD)
DRUGPlacebo capsules
Placebo capsules to match AZD7268
DRUGPlacebo tablets
Placebo tablets to match encapsulated escitalopram
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 65 Years
Healthy volunteers
No
Inclusion criteria
* Provision of signed, written, and dated Informed Consent prior to any study specific procedures * Documented primary clinical diagnosis meeting criteria from the DSM-IV, Text Revision (APA 2000) for any of the following: * 296.2x Major Depressive Disorder, Single Episode, or * 296.3x Major Depressive Disorder, Recurrent
Exclusion criteria
* Patients with a secondary DSM-IV Axis I disorder other than GAD or social anxiety disorder (as assessed by MINI), provided the primary diagnosis is MDD. This diagnosis should have been made at least 6 months before enrollment * Patients with a diagnosis of DSM-IV Axis II disorder which has a major impact on the patient's current psychiatric status * Patients whose current episode of depression started less than 4 weeks before enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score Change From Baseline to Week 4. | Baseline, Week 4 | MADRS total score, sum of 10 item scores (each on a 0 (best value) to 6 (worst value)scale), assesses the severity of depressive symptoms on a continuous scale from 0 (the best) to 60 (the worst). Change from baseline was calculated as Week 4 value minus baseline value. \[observed cases, Mixed Model Repeated Measurement (MMRM), Full Analysis Set (FAS)\] |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Montgomery-Åsberg Depression Rating Scale (MADRS) Response | Week 4 | Number of patients with MADRS response at Week 4. MADRS response is defined as \>=50% reduction in MADRS total score from baseline. MADRS total score, sum of 10 item scores (each on a 0 (best value) to 6 (worst value)scale), assesses the severity of depressive symptoms on a continuous scale from 0 (the best) to 60 (the worst). MADRS response at Week 4 is calculated using last observation carried forward (LOCF). \[Full Analysis Set (FAS)\] |
| Montgomery-Åsberg Depression Rating Scale (MADRS) Remission | Week 4 | Number of patients, who achieved MADRS remission at week 4. Remission is defined as a MADRS total score \<= 10. MADRS total score, sum of 10 item scores (each on a 0 (best value) to 6 (worst value)scale), assesses the severity of depressive symptoms on a continuous scale from 0 (the best) to 60 (the worst). MADRS remission at Week 4 is calculated using last observation carried forward (LOCF). \[Full Analysis Set (FAS)\] |
| Hamilton Rating Scale for Depression (HAM-D) Total Score Change From Baseline to Week 4. | Baseline, Week 4 | HAM-D total score, sum of 17 item scores (each on a 0 to 2 or 0 to 4 scale), assesses the severity of depressive symptoms on a continuous scale from 0 (the best) to 52 (the worst). Change from baseline to Week 4 was calculated as Week 4 value minus baseline value. \[observed cases, Mixed Model Repeated Measurement (MMRM), Full Analysis Set (FAS)\] |
| Clinical Global Impression - Severity (CGI-S) Score Change From Baseline | Baseline, Week 4 | CGI-S assesses global illness severity, i.e. the patient's current clinical state, on a continuous scale from 1 (Normal, not ill) to 7 (Among the most extremely ill patients). Change from baseline to Week 4 was calculated as Week 4 value minus baseline value. \[observed cases, Mixed Model Repeated Measurement (MMRM), Full Analysis Set (FAS)\] |
| Hamilton Rating Scale for Anxiety (HAM-A) Total Score Change From Baseline | Baseline, Week 4 | HAM-A total score, sum of 14 item scores (each on a 0 to 4 scale), assesses the severity of anxiety symptoms on a continuous scale from 0 (the best) to 52 (the worst). Change from baseline to Week 4 was calculated as Week 4 value minus baseline value. \[observed cases, Mixed Model Repeated Measurement (MMRM), Full Analysis Set (FAS)\] |
Countries
United States
Participant flow
Recruitment details
A total of 18 centers were inititated with first patient enrolled on 16 November 2009 and last patient completed on 15 April 2010. A total of 430 patients were enrolled with 247 qualified patients allocated to randomized treatment.
Pre-assignment details
Patients were required to discontinue current treatment for MDD at least 7 days prior to randomization (14 days prior to Day 1 for monoamine oxidase inhibitors \[MAOIs\] and 28 days prior to Day 1 for fluoxetine). Patients not taking medications for MDD at enrollment could be randomized once eligibility was confirmed.
Participants by arm
| Arm | Count |
|---|---|
| AZD7268 AZD7268 15 mg twice per day (BID), placebo matching escitalopram | 98 |
| Placebo Placebo matching both AZD7268 and escitalopram | 99 |
| Escitalopram Escitalopram 20 mg once per day(QD) Placebo matching AZD7268 | 50 |
| Total | 247 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 3 | 2 |
| Overall Study | Lost to Follow-up | 6 | 4 | 2 |
| Overall Study | non-compliance; lack of efficacy; etc. | 4 | 3 | 0 |
| Overall Study | Protocol Violation | 3 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 2 | 3 |
Baseline characteristics
| Characteristic | Total | Escitalopram | Placebo | AZD7268 |
|---|---|---|---|---|
| Age Continuous | 39.09 Years STANDARD_DEVIATION 10.98 | 36.22 Years STANDARD_DEVIATION 11.29 | 41.77 Years STANDARD_DEVIATION 10.02 | 39.29 Years STANDARD_DEVIATION 11.63 |
| Hamilton Rating Scale for Depression (HAM-D) total score at baseline | 24.43 scores on a scale STANDARD_DEVIATION 2.83 | 24.4 scores on a scale STANDARD_DEVIATION 2.8 | 24.6 scores on a scale STANDARD_DEVIATION 2.8 | 24.3 scores on a scale STANDARD_DEVIATION 2.9 |
| Montgomery-Åsberg Depression Rating Scale (MADRS) total score at baseline | 31.03 scores on a scale STANDARD_DEVIATION 4.03 | 30.8 scores on a scale STANDARD_DEVIATION 4 | 31.4 scores on a scale STANDARD_DEVIATION 4.2 | 30.9 scores on a scale STANDARD_DEVIATION 3.9 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 5 Participants | 1 Participants | 4 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 77 Participants | 15 Participants | 35 Participants | 27 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 2 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 6 Participants | 0 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 156 Participants | 34 Participants | 56 Participants | 66 Participants |
| Sex: Female, Male Female | 108 Participants | 22 Participants | 49 Participants | 37 Participants |
| Sex: Female, Male Male | 139 Participants | 28 Participants | 50 Participants | 61 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 | 36 / 96 | 33 / 99 | 26 / 50 |
| serious Total, serious adverse events | 0 / 96 | 0 / 99 | 0 / 50 |
Outcome results
Primary
Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score Change From Baseline to Week 4.
MADRS total score, sum of 10 item scores (each on a 0 (best value) to 6 (worst value)scale), assesses the severity of depressive symptoms on a continuous scale from 0 (the best) to 60 (the worst). Change from baseline was calculated as Week 4 value minus baseline value. \[observed cases, Mixed Model Repeated Measurement (MMRM), Full Analysis Set (FAS)\]
Time frame: Baseline, Week 4
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AZD7268 | Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score Change From Baseline to Week 4. | -11.78 scores on a scale | Standard Error 1.13 |
| Placebo | Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score Change From Baseline to Week 4. | -11.45 scores on a scale | Standard Error 1.05 |
| Escitalopram | Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score Change From Baseline to Week 4. | -11.70 scores on a scale | Standard Error 1.57 |
Secondary
Clinical Global Impression - Severity (CGI-S) Score Change From Baseline
CGI-S assesses global illness severity, i.e. the patient's current clinical state, on a continuous scale from 1 (Normal, not ill) to 7 (Among the most extremely ill patients). Change from baseline to Week 4 was calculated as Week 4 value minus baseline value. \[observed cases, Mixed Model Repeated Measurement (MMRM), Full Analysis Set (FAS)\]
Time frame: Baseline, Week 4
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AZD7268 | Clinical Global Impression - Severity (CGI-S) Score Change From Baseline | -1.26 scores on a scale | Standard Error 0.13 |
| Placebo | Clinical Global Impression - Severity (CGI-S) Score Change From Baseline | -1.15 scores on a scale | Standard Error 0.13 |
| Escitalopram | Clinical Global Impression - Severity (CGI-S) Score Change From Baseline | -1.31 scores on a scale | Standard Error 0.17 |
Secondary
Hamilton Rating Scale for Anxiety (HAM-A) Total Score Change From Baseline
HAM-A total score, sum of 14 item scores (each on a 0 to 4 scale), assesses the severity of anxiety symptoms on a continuous scale from 0 (the best) to 52 (the worst). Change from baseline to Week 4 was calculated as Week 4 value minus baseline value. \[observed cases, Mixed Model Repeated Measurement (MMRM), Full Analysis Set (FAS)\]
Time frame: Baseline, Week 4
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AZD7268 | Hamilton Rating Scale for Anxiety (HAM-A) Total Score Change From Baseline | -5.30 scores on a scale | Standard Error 0.6 |
| Placebo | Hamilton Rating Scale for Anxiety (HAM-A) Total Score Change From Baseline | -4.66 scores on a scale | Standard Error 0.61 |
| Escitalopram | Hamilton Rating Scale for Anxiety (HAM-A) Total Score Change From Baseline | -6.15 scores on a scale | Standard Error 0.78 |
Secondary
Hamilton Rating Scale for Depression (HAM-D) Total Score Change From Baseline to Week 4.
HAM-D total score, sum of 17 item scores (each on a 0 to 2 or 0 to 4 scale), assesses the severity of depressive symptoms on a continuous scale from 0 (the best) to 52 (the worst). Change from baseline to Week 4 was calculated as Week 4 value minus baseline value. \[observed cases, Mixed Model Repeated Measurement (MMRM), Full Analysis Set (FAS)\]
Time frame: Baseline, Week 4
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AZD7268 | Hamilton Rating Scale for Depression (HAM-D) Total Score Change From Baseline to Week 4. | -9.22 scores on a scale | Standard Error 0.82 |
| Placebo | Hamilton Rating Scale for Depression (HAM-D) Total Score Change From Baseline to Week 4. | -9.15 scores on a scale | Standard Error 0.81 |
| Escitalopram | Hamilton Rating Scale for Depression (HAM-D) Total Score Change From Baseline to Week 4. | -9.84 scores on a scale | Standard Error 0.99 |
Secondary
Montgomery-Åsberg Depression Rating Scale (MADRS) Remission
Number of patients, who achieved MADRS remission at week 4. Remission is defined as a MADRS total score \<= 10. MADRS total score, sum of 10 item scores (each on a 0 (best value) to 6 (worst value)scale), assesses the severity of depressive symptoms on a continuous scale from 0 (the best) to 60 (the worst). MADRS remission at Week 4 is calculated using last observation carried forward (LOCF). \[Full Analysis Set (FAS)\]
Time frame: Week 4
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZD7268 | Montgomery-Åsberg Depression Rating Scale (MADRS) Remission | 20 Participants |
| Placebo | Montgomery-Åsberg Depression Rating Scale (MADRS) Remission | 12 Participants |
| Escitalopram | Montgomery-Åsberg Depression Rating Scale (MADRS) Remission | 10 Participants |
Secondary
Montgomery-Åsberg Depression Rating Scale (MADRS) Response
Number of patients with MADRS response at Week 4. MADRS response is defined as \>=50% reduction in MADRS total score from baseline. MADRS total score, sum of 10 item scores (each on a 0 (best value) to 6 (worst value)scale), assesses the severity of depressive symptoms on a continuous scale from 0 (the best) to 60 (the worst). MADRS response at Week 4 is calculated using last observation carried forward (LOCF). \[Full Analysis Set (FAS)\]
Time frame: Week 4
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZD7268 | Montgomery-Åsberg Depression Rating Scale (MADRS) Response | 31 Participants |
| Placebo | Montgomery-Åsberg Depression Rating Scale (MADRS) Response | 31 Participants |
| Escitalopram | Montgomery-Åsberg Depression Rating Scale (MADRS) Response | 14 Participants |