Major Depressive Disorder
Conditions
Brief summary
The purpose of this study is to evaluate the long-term safety and tolerability of vilazodone for the treatment of MDD in pediatric outpatients (7-17 years).
Interventions
DRUGVilazodone
Vilazodone tablets, once daily, oral administration
Sponsors
Forest Laboratories
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
7 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Male or Female outpatients betw een 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, Fourth Edition, Text Revision based diagnosis of an Axis I disorder other than MDD that is the primary focus of treatment (de novo patients only) * History of suicidal behavior, or requires precaution against suicide * Not generally healthy medical condition * Seizure disorder
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants to Experience a Treatment Emergent Adverse Event (TEAE) | Visit 1 (Week -1) to up to Visit 16 (Week 26) | The number of Participants who experienced a treatment emergent adverse events during the 27 week period from screening to the end of the open-label treatment period |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the CDRS-R Total Score | Baseline (Week 0) to Week 26 | 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. |
| Change From Baseline in the CGI-S Score | Baseline (Week 0) to Week 26 | 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. |
| Change From Baseline in Clinical Global Impressions-Improvement (CGI-I) | Baseline (Week 0) to Week 26 | The Clinical Global Impressions-Improvement is a clinician-rated instrument that was used to rate total improvement or worsening of mental illness, regardless of whether the Investigator considered it to be a result of treatment with the investigational product. The CGI-I was used to rate the patient's improvement on a scale from 1 to 7, with 1 indicating that the patient was very much improved (with a score of 4 indicating no change) and 7 indicating the patient was very much worse. |
Countries
Canada, United States
Participant flow
Pre-assignment details
Patients who completed lead-in study VLZ-MD-22 (NCT02372799) had already completed a down-taper period at the end of study VLZ-MD-22 and were not required to undergo a washout period in VLZ-MD-23. For de novo patients, the screening/washout period was generally 1 week prior to Baseline.
Participants by arm
| Arm | Count |
|---|---|
| Placebo/Vilazodone Participants who received placebo during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration. | 122 |
| Vilazodone/Vilazodone Participants who received vilazodone during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration. | 131 |
| Fluoxetine/Vilazodone Participants who received Fluoxetine during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration. | 65 |
| De Novo/Vilazodone Newly enrolled participants received vilazodone tablets once daily, oral administration. | 12 |
| Total | 330 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Down-Taper Period | Withdrawal by Subject | 4 | 4 | 1 | 2 |
| Open-Lable Treatment Period | Adverse Event | 12 | 3 | 4 | 2 |
| Open-Lable Treatment Period | Lack of Efficacy | 1 | 6 | 6 | 1 |
| Open-Lable Treatment Period | Lost to Follow-up | 4 | 2 | 4 | 1 |
| Open-Lable Treatment Period | Noncompliance with Study Drug | 5 | 6 | 3 | 1 |
| Open-Lable Treatment Period | Other Reason | 1 | 1 | 0 | 0 |
| Open-Lable Treatment Period | Protocol Violation | 0 | 1 | 1 | 0 |
| Open-Lable Treatment Period | Withdrawal by Subject | 10 | 15 | 9 | 0 |
Baseline characteristics
| Characteristic | Placebo/Vilazodone | Vilazodone/Vilazodone | Fluoxetine/Vilazodone | De Novo/Vilazodone | Total |
|---|---|---|---|---|---|
| Age, Continuous | 13.2 Years STANDARD_DEVIATION 2.9 | 13.3 Years STANDARD_DEVIATION 2.8 | 13.2 Years STANDARD_DEVIATION 2.8 | 13.0 Years STANDARD_DEVIATION 2.9 | 13.3 Years STANDARD_DEVIATION 2.9 |
| Age, Customized Age 12-17 Years | 83 Participants | 93 Participants | 46 Participants | 8 Participants | 230 Participants |
| Age, Customized Age 18 Years | 2 Participants | 3 Participants | 0 Participants | 0 Participants | 5 Participants |
| Age, Customized Age 7-11 Years | 37 Participants | 35 Participants | 19 Participants | 4 Participants | 95 Participants |
| Body Mass Index (BMI) | 22.73 kg/m^2 STANDARD_DEVIATION 6.59 | 24.75 kg/m^2 STANDARD_DEVIATION 7.96 | 23.30 kg/m^2 STANDARD_DEVIATION 5.37 | 23.90 kg/m^2 STANDARD_DEVIATION 6.2 | 23.69 kg/m^2 STANDARD_DEVIATION 6.98 |
| CDRS-R total score | 55.7 units on a scale STANDARD_DEVIATION 9.6 | 59.3 units on a scale STANDARD_DEVIATION 9.5 | 57.8 units on a scale STANDARD_DEVIATION 8.7 | 59.7 units on a scale STANDARD_DEVIATION 9.1 | 58.4 units on a scale STANDARD_DEVIATION 9.3 |
| CGI-S score | 4.6 units on a scale STANDARD_DEVIATION 0.6 | 4.7 units on a scale STANDARD_DEVIATION 0.7 | 4.6 units on a scale STANDARD_DEVIATION 0.6 | 4.2 units on a scale STANDARD_DEVIATION 0.4 | 4.6 units on a scale STANDARD_DEVIATION 0.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 16 Participants | 16 Participants | 8 Participants | 2 Participants | 42 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 106 Participants | 115 Participants | 57 Participants | 10 Participants | 288 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 1 Participants | 1 Participants | 0 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 32 Participants | 40 Participants | 20 Participants | 1 Participants | 93 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 4 Participants | 2 Participants | 0 Participants | 9 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 82 Participants | 84 Participants | 42 Participants | 11 Participants | 219 Participants |
| Sex: Female, Male Female | 68 Participants | 89 Participants | 33 Participants | 7 Participants | 197 Participants |
| Sex: Female, Male Male | 54 Participants | 42 Participants | 32 Participants | 5 Participants | 133 Participants |
| Weight | 57.98 kg STANDARD_DEVIATION 23.54 | 62.67 kg STANDARD_DEVIATION 25.26 | 59.36 kg STANDARD_DEVIATION 18.93 | 60.34 kg STANDARD_DEVIATION 17.87 | 60.17 kg STANDARD_DEVIATION 23.26 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 122 | 0 / 131 | 1 / 65 | 0 / 12 |
| other Total, other adverse events | 79 / 122 | 81 / 131 | 41 / 65 | 10 / 12 |
| serious Total, serious adverse events | 6 / 122 | 0 / 131 | 1 / 65 | 0 / 12 |
Outcome results
Primary
Number of Participants to Experience a Treatment Emergent Adverse Event (TEAE)
The number of Participants who experienced a treatment emergent adverse events during the 27 week period from screening to the end of the open-label treatment period
Time frame: Visit 1 (Week -1) to up to Visit 16 (Week 26)
Population: The Safety Population consisted of the 330 participants who took at least 1 dose of open-label investigational product.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo/Vilazodone | Number of Participants to Experience a Treatment Emergent Adverse Event (TEAE) | 90 Participants |
| Vilazodone/Vilazodone | Number of Participants to Experience a Treatment Emergent Adverse Event (TEAE) | 89 Participants |
| Fluoxetine/Vilazodone | Number of Participants to Experience a Treatment Emergent Adverse Event (TEAE) | 48 Participants |
| De Novo/Vilazodone | Number of Participants to Experience a Treatment Emergent Adverse Event (TEAE) | 10 Participants |
Secondary
Change From Baseline in Clinical Global Impressions-Improvement (CGI-I)
The Clinical Global Impressions-Improvement is a clinician-rated instrument that was used to rate total improvement or worsening of mental illness, regardless of whether the Investigator considered it to be a result of treatment with the investigational product. The CGI-I was used to rate the patient's improvement on a scale from 1 to 7, with 1 indicating that the patient was very much improved (with a score of 4 indicating no change) and 7 indicating the patient was very much worse.
Time frame: Baseline (Week 0) to Week 26
Population: The CGI-I was assessed in the Intent to Treat study population, comprised of the 325 patients in the Safety Population who had a baseline and at least 1 postbaseline assessment of the CDRS-R total score.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Vilazodone | Change From Baseline in Clinical Global Impressions-Improvement (CGI-I) | 2.1 units on a scale | Standard Deviation 1.2 |
| Vilazodone/Vilazodone | Change From Baseline in Clinical Global Impressions-Improvement (CGI-I) | 2.0 units on a scale | Standard Deviation 1.3 |
| Fluoxetine/Vilazodone | Change From Baseline in Clinical Global Impressions-Improvement (CGI-I) | 2.0 units on a scale | Standard Deviation 1.2 |
| De Novo/Vilazodone | Change From Baseline in Clinical Global Impressions-Improvement (CGI-I) | 2.2 units on a scale | Standard Deviation 1.2 |
Secondary
Change From Baseline in the 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: Baseline (Week 0) to Week 26
Population: The Change From Baseline in the CDRS-R Total Score was assessed in the Intent to Treat study population, comprised of the 325 patients in the Safety Population who had a baseline and at least 1 postbaseline assessment of the CDRS-R total score.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Vilazodone | Change From Baseline in the CDRS-R Total Score | -29.2 units on a scale | Standard Deviation 11.9 |
| Vilazodone/Vilazodone | Change From Baseline in the CDRS-R Total Score | -30.1 units on a scale | Standard Deviation 12.2 |
| Fluoxetine/Vilazodone | Change From Baseline in the CDRS-R Total Score | -29.4 units on a scale | Standard Deviation 12.2 |
| De Novo/Vilazodone | Change From Baseline in the CDRS-R Total Score | -24.5 units on a scale | Standard Deviation 10.3 |
Secondary
Change From Baseline in the 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: Baseline (Week 0) to Week 26
Population: The CGI-S was assessed in the Intent to Treat study population, comprised of the 325 patients in the Safety Population who had a baseline and at least 1 postbaseline assessment of the CDRS-R total score.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Vilazodone | Change From Baseline in the CGI-S Score | -2.5 units on a scale | Standard Deviation 1.3 |
| Vilazodone/Vilazodone | Change From Baseline in the CGI-S Score | -2.6 units on a scale | Standard Deviation 1.4 |
| Fluoxetine/Vilazodone | Change From Baseline in the CGI-S Score | -2.5 units on a scale | Standard Deviation 1.4 |
| De Novo/Vilazodone | Change From Baseline in the CGI-S Score | -1.7 units on a scale | Standard Deviation 1.2 |