Major Depressive Disorder
Conditions
Keywords
Major depressive disorder, Depression
Brief summary
The purpose of this study was to further characterize the efficacy, safety, and tolerability of a single fixed dose level of vilazodone compared to placebo in patients with major depressive disorder.
Interventions
Dose-matched placebo was supplied as tablets.
DRUGVilazodone
Vilazodone was supplied as tablets.
Sponsors
Forest Laboratories
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Men and women, 18-70 years of age. * Currently meet the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR) criteria for Major Depressive Disorder. * The patient's current major depressive episode must be at least 8 weeks and no longer than 12 months in duration.
Exclusion criteria
* Women who are pregnant, women who will be breastfeeding during the study, and women of childbearing potential who are not practicing a reliable method of birth control. * Patients with a history of meeting DSM-IV-TR criteria for any: * manic, hypomanic or mixed episode, including bipolar disorder and substance-induced manic, hypomanic, or mixed episode; * any depressive episode with psychotic or catatonic features; * panic disorder with or without agoraphobia; * obsessive-compulsive disorder; * schizophrenia, schizoaffective, or other psychotic disorder; * bulimia or anorexia nervosa; * presence of borderline personality disorder or antisocial personality disorder; * mental retardation, dementia, amnesia, or other cognitive disorders; * patients who are considered a suicide risk.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 8 | Baseline to Week 8 | The MADRS is a clinician-rated scale for assessing depressive symptomatology that had occurred in participants during the week preceding each interview. Patients were rated on 10 items to assess feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and lack of interest. Each item was scored on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score was the sum of the scores on the 10 items and ranged from 0 to 60. A higher score indicated more depressive symptomatology. A negative change score indicated improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Clinical Global Impressions-Severity (CGI-S) Score at Week 8 | Baseline to Week 8 | The CGI-S is a clinician-rated scale for assessing the severity of the participant's current state of mental illness compared with a patient population with major depressive disorder. The clinician responded to the following question Considering your total clinical experience with this population, how mentally ill is the participant at this time? on a 7-point scale: 1=normal, not at all ill; 2=borderline ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill patients. The scale ranges from 1 to 7. A higher score indicates more severe mental illness. A negative change score indicates improvement. |
| Percentage of Participants With a Montgomery-Åsberg Depression Rating Scale (MADRS) Sustained Response Rate | Baseline to Week 8 | The MADRS Sustained response rate is defined as a MÅDRS total score ≤ 12 for at least the last 2 consecutive visits during the double-blind treatment period. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dose-matched Placebo Participants received dose-matched placebo orally once daily for 9 weeks. | 253 |
| Vilazodone Participants received vilazodone orally once daily for 9 weeks, as follows: Week 1, 10 mg once a day; Week 2, 20 mg once a day; Weeks 3 to 8, 40 mg once a day; and Week 9 (down-taper period), 20 mg once a day for 4 days, then 10 mg once a day for 3 days. | 255 |
| Total | 508 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 13 | 16 |
| Overall Study | Insufficient Therapeutic Response | 4 | 1 |
| Overall Study | Lost to Follow-up | 9 | 11 |
| Overall Study | Protocol Violation | 7 | 5 |
| Overall Study | Withdrew Consent | 12 | 10 |
Baseline characteristics
| Characteristic | Vilazodone | Dose-matched Placebo | Total |
|---|---|---|---|
| Age, Continuous | 39.3 Years STANDARD_DEVIATION 12.8 | 41.1 Years STANDARD_DEVIATION 13.2 | 40.2 Years STANDARD_DEVIATION 13 |
| Age, Customized < 20 | 6 Participants | 7 Participants | 13 Participants |
| Age, Customized ≥ 20-29 | 68 Participants | 53 Participants | 121 Participants |
| Age, Customized ≥ 30-39 | 56 Participants | 54 Participants | 110 Participants |
| Age, Customized ≥ 40-49 | 62 Participants | 67 Participants | 129 Participants |
| Age, Customized ≥ 50-59 | 44 Participants | 48 Participants | 92 Participants |
| Age, Customized ≥ 60 | 19 Participants | 24 Participants | 43 Participants |
| Body mass index | 28.41 kg/m^2 STANDARD_DEVIATION 5.47 | 29.08 kg/m^2 STANDARD_DEVIATION 5.5 | 28.75 kg/m^2 STANDARD_DEVIATION 5.49 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 42 Participants | 33 Participants | 75 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 213 Participants | 220 Participants | 433 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Height | 170.32 cm STANDARD_DEVIATION 9.6 | 170.15 cm STANDARD_DEVIATION 9.12 | 170.23 cm STANDARD_DEVIATION 9.36 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 4 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized Asian | 14 Participants | 7 Participants | 21 Participants |
| Race/Ethnicity, Customized Black or African American | 52 Participants | 70 Participants | 122 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 11 Participants | 7 Participants | 18 Participants |
| Race/Ethnicity, Customized White | 174 Participants | 168 Participants | 342 Participants |
| Sex: Female, Male Female | 131 Participants | 142 Participants | 273 Participants |
| Sex: Female, Male Male | 124 Participants | 111 Participants | 235 Participants |
| Weight | 82.89 kg STANDARD_DEVIATION 18.39 | 84.68 kg STANDARD_DEVIATION 17.84 | 83.78 kg STANDARD_DEVIATION 18.12 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 78 / 253 | 149 / 255 |
| serious Total, serious adverse events | 2 / 253 | 3 / 255 |
Outcome results
Primary
Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 8
The MADRS is a clinician-rated scale for assessing depressive symptomatology that had occurred in participants during the week preceding each interview. Patients were rated on 10 items to assess feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and lack of interest. Each item was scored on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score was the sum of the scores on the 10 items and ranged from 0 to 60. A higher score indicated more depressive symptomatology. A negative change score indicated improvement.
Time frame: Baseline to Week 8
Population: Intent-to-treat population: All randomized participants who received at least 1 dose of double-blind investigational product and who had a Baseline and at least 1 post-baseline assessment of the MADRS total score.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Dose-matched Placebo | Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 8 | -11.0 Units on a scale | Standard Error 0.65 |
| Vilazodone | Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 8 | -16.1 Units on a scale | Standard Error 0.64 |
p-value: <0.0000195% CI: [-6.886, -3.347]Mixed-effects model for repeated measure
Secondary
Change From Baseline in Clinical Global Impressions-Severity (CGI-S) Score at Week 8
The CGI-S is a clinician-rated scale for assessing the severity of the participant's current state of mental illness compared with a patient population with major depressive disorder. The clinician responded to the following question Considering your total clinical experience with this population, how mentally ill is the participant at this time? on a 7-point scale: 1=normal, not at all ill; 2=borderline ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill patients. The scale ranges from 1 to 7. A higher score indicates more severe mental illness. A negative change score indicates improvement.
Time frame: Baseline to Week 8
Population: Intent-to-treat population: All randomized participants who received at least 1 dose of double-blind investigational product and who had a Baseline and at least 1 post-baseline assessment of the MADRS total score.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Dose-matched Placebo | Change From Baseline in Clinical Global Impressions-Severity (CGI-S) Score at Week 8 | -1.2 Units on a scale | Standard Error 0.08 |
| Vilazodone | Change From Baseline in Clinical Global Impressions-Severity (CGI-S) Score at Week 8 | -1.8 Units on a scale | Standard Error 0.08 |
p-value: <0.0000195% CI: [-0.845, -0.399]Mixed-effects model for repeated measure
Secondary
Percentage of Participants With a Montgomery-Åsberg Depression Rating Scale (MADRS) Sustained Response Rate
The MADRS Sustained response rate is defined as a MÅDRS total score ≤ 12 for at least the last 2 consecutive visits during the double-blind treatment period.
Time frame: Baseline to Week 8
Population: Intent-to-treat population: All randomized participants who received at least 1 dose of double-blind investigational product and who had a Baseline and at least 1 post-baseline assessment of the MADRS total score.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose-matched Placebo | Percentage of Participants With a Montgomery-Åsberg Depression Rating Scale (MADRS) Sustained Response Rate | 17.1 Percentage of participants |
| Vilazodone | Percentage of Participants With a Montgomery-Åsberg Depression Rating Scale (MADRS) Sustained Response Rate | 27.3 Percentage of participants |
p-value: 0.004795% CI: [3, 17.4]Cochran-Mantel-Haenszel