Major Depressive Disorder
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy, safety, and tolerability of vilazodone compared with placebo in pediatric outpatients (7-17 years of age) with major depressive disorder.
Interventions
DRUGVilazodone
DRUGPlacebo
DRUGFluoxetine
Sponsors
Forest Laboratories
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
7 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Male or Female outpatients between 7-17 years of age * Primary diagnosis of Major Depressive Disorder (MDD) * Children's Depression Rating Scale-Revised (CDRS-R) score of 40 or greater * Clinical Global Impressions-Severity (CGI-S) score of 4 or greater
Exclusion criteria
* Current (past 3 months) principal Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision (DSM-IV-TR) based diagnosis of an axis disorder other than major depressive disorder (MDD) that is the primary focus of treatment. * History of suicidal behavior, or requires precaution against suicide * Not generally healthy medical condition * Seizure disorder
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Children's Depression Rating Scale-Revised (CDRS-R) Total Score | From Baseline to Week 8 | The Children's Depression Rating Scale-Revised (CDRS-R) total score ranges from 17 (minimal or no symptoms of depression) to 133 (indicative of depression) is a semi-structured, clinician-rated instrument designed for use with children and adolescents between the ages of 6 to 17 years of age and their caregivers. The CDRS-R evaluates the presence and severity of symptoms commonly associated with depression in childhood. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Clinical Global Impressions-Severity (CGI-S) Score | From Baseline to Week 8 | The Clinical Global Impressions-Severity (CGI-S) is a clinician-rated instrument used to rate the severity of the patient's current state of mental illness compared with the clinician's total experience with patients with major depressive disorder (MDD). The severity of the patient's MDD was rated on a scale from 1 to 7, with 1 indicating a normal state and 7 indicating a patient who is among the most extremely ill patients. |
Countries
Canada, United States
Participant flow
Pre-assignment details
Randomization and treatment assignment were based on a randomization scheme prepared by Allergan Biostatistics prior to the start of the study
Participants by arm
| Arm | Count |
|---|---|
| Placebo Dose-matched placebo tablets or capsules, oral administration, once per day. | 186 |
| Vilazodone Vilazodone tablets 15-30 mg. Oral administration, once per day. | 187 |
| Fluoxetine Fluoxetine capsules 20 mg. Oral administration, once per day. | 97 |
| Total | 470 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Down-taper Period | Lost to Follow-up | 1 | 2 | 2 |
| Treatment Period | Adverse Event | 3 | 10 | 6 |
| Treatment Period | Insufficient therapeutic response | 2 | 2 | 0 |
| Treatment Period | Lost to Follow-up | 11 | 5 | 3 |
| Treatment Period | Miscellaneous Reasons | 1 | 1 | 0 |
| Treatment Period | Non-compliance with study drug | 4 | 4 | 4 |
| Treatment Period | Protocol Violation | 3 | 0 | 0 |
| Treatment Period | Withdrawal by Subject | 10 | 10 | 2 |
Baseline characteristics
| Characteristic | Placebo | Vilazodone | Fluoxetine | Total |
|---|---|---|---|---|
| Age, Continuous | 13 Years STANDARD_DEVIATION 2.9 | 13 Years STANDARD_DEVIATION 2.9 | 13.2 Years STANDARD_DEVIATION 2.8 | 13 Years STANDARD_DEVIATION 2.9 |
| Age, Customized 12-17 | 125 Participants | 132 Participants | 67 Participants | 324 Participants |
| Age, Customized 7-11 | 61 Participants | 55 Participants | 30 Participants | 146 Participants |
| Body Mass Index (BMI) | 23.31 kg/m2 STANDARD_DEVIATION 6.85 | 24.25 kg/m2 STANDARD_DEVIATION 7.58 | 23.48 kg/m2 STANDARD_DEVIATION 6.66 | 23.72 kg/m2 STANDARD_DEVIATION 7.11 |
| CDRS-R total score | 57.3 units on a scale STANDARD_DEVIATION 9.2 | 58.3 units on a scale STANDARD_DEVIATION 9.2 | 58 units on a scale STANDARD_DEVIATION 8.8 | 57.8 units on a scale STANDARD_DEVIATION 9.1 |
| CGI-S score | 4.6 Units on a Scale STANDARD_DEVIATION 0.6 | 4.7 Units on a Scale STANDARD_DEVIATION 0.6 | 4.6 Units on a Scale STANDARD_DEVIATION 0.6 | 4.6 Units on a Scale STANDARD_DEVIATION 0.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 27 Participants | 25 Participants | 12 Participants | 64 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 159 Participants | 162 Participants | 85 Participants | 406 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 5 Participants | 1 Participants | 1 Participants | 7 Participants |
| Race/Ethnicity, Customized Black or African American | 57 Participants | 58 Participants | 30 Participants | 145 Participants |
| Race/Ethnicity, Customized Missing | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants | 2 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Other | 5 Participants | 5 Participants | 5 Participants | 15 Participants |
| Race/Ethnicity, Customized White | 118 Participants | 121 Participants | 60 Participants | 299 Participants |
| Sex: Female, Male Female | 106 Participants | 126 Participants | 51 Participants | 283 Participants |
| Sex: Female, Male Male | 80 Participants | 61 Participants | 46 Participants | 187 Participants |
| Weight | 59.13 kg STANDARD_DEVIATION 24.29 | 61.35 kg STANDARD_DEVIATION 24.79 | 59.38 kg STANDARD_DEVIATION 21.14 | 60.07 kg STANDARD_DEVIATION 23.86 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 186 | 0 / 187 | 0 / 97 |
| other Total, other adverse events | 54 / 186 | 97 / 187 | 27 / 97 |
| serious Total, serious adverse events | 1 / 186 | 0 / 187 | 6 / 97 |
Outcome results
Primary
Change in Children's Depression Rating Scale-Revised (CDRS-R) Total Score
The Children's Depression Rating Scale-Revised (CDRS-R) total score ranges from 17 (minimal or no symptoms of depression) to 133 (indicative of depression) is a semi-structured, clinician-rated instrument designed for use with children and adolescents between the ages of 6 to 17 years of age and their caregivers. The CDRS-R evaluates the presence and severity of symptoms commonly associated with depression in childhood.
Time frame: From Baseline to Week 8
Population: The Intent-to-Treat (ITT) Population will consist of all patients in the Safety Population who had baseline and at least 1 postbaseline assessment of the Children's Depression Rating Scale-Revised (CDRS-R) total score.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Children's Depression Rating Scale-Revised (CDRS-R) Total Score | -20.32 units on a scale | Standard Error 0.983 |
| Vilazodone | Change in Children's Depression Rating Scale-Revised (CDRS-R) Total Score | -20.72 units on a scale | Standard Error 0.977 |
| Fluoxetine | Change in Children's Depression Rating Scale-Revised (CDRS-R) Total Score | -22.71 units on a scale | Standard Error 1.32 |
p-value: 0.766295% CI: [-3.08, 2.27]MMRM
p-value: 0.143395% CI: [-5.6, 0.81]MMRM
Secondary
Change in Clinical Global Impressions-Severity (CGI-S) Score
The Clinical Global Impressions-Severity (CGI-S) is a clinician-rated instrument used to rate the severity of the patient's current state of mental illness compared with the clinician's total experience with patients with major depressive disorder (MDD). The severity of the patient's MDD was rated on a scale from 1 to 7, with 1 indicating a normal state and 7 indicating a patient who is among the most extremely ill patients.
Time frame: From Baseline to Week 8
Population: The Intent-to-Treat (ITT) Population will consist of all patients in the Safety Population who had baseline and at least 1 postbaseline assessment of the Children's Depression Rating Scale-Revised (CDRS-R) total score.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Clinical Global Impressions-Severity (CGI-S) Score | -1.52 units on a scale | Standard Error 0.097 |
| Vilazodone | Change in Clinical Global Impressions-Severity (CGI-S) Score | -1.57 units on a scale | Standard Error 0.096 |
| Fluoxetine | Change in Clinical Global Impressions-Severity (CGI-S) Score | -1.72 units on a scale | Standard Error 0.13 |
p-value: 0.738795% CI: [-0.31, 0.22]MMRM
p-value: 0.215895% CI: [-0.52, 0.12]MMRM