Major Depressive Disorder
Conditions
Keywords
Depression, Major Depressive Disorder
Brief summary
The purpose of this study is to evaluate the efficacy, safety, and tolerability of Levomilnacipran ER versus placebo in the treatment of outpatients with major depressive disorder
Interventions
Levomilnacipran ER capsules, flexible dose, oral administration, once daily dosing. Study drug is to be given orally, in capsule form, once daily, for 8 weeks
DRUGPlacebo
Matching placebo to be given orally, in capsule form, once daily, for 8 weeks.
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 80 Years
Healthy volunteers
No
Inclusion criteria
* Men and women, 18-80 years old * Currently meet the DSM-IV-TR criteria for Major Depressive Disorder * The patient's current depressive episode must be at least 4 weeks in duration
Exclusion criteria
* Women who are pregnant, women who will be breastfeeding during the study, and women with childbearing potential who are not practicing a reliable method of birth control. * Patients with a history of meeting DSM-IV-TR criteria for: a. any manic or hypomanic episode; b. schizophrenia or any other psychotic disorder; c. obsessive-compulsive disorder. * Patients who are considered a suicide risk
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | From Baseline to Week 8 | MADRS was used to assess depressive symptomatology during the past week. Patients are 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 of the 10 items are scored on a 7-point scale. A score of 0 indicates the absence of symptoms,and a score of 6 indicates symptoms of maximum severity. The total MADRS score for this measure ranges from 0 (absence of symptoms) to 60 (maximum severity). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Sheehan Disability Scale (SDS) Total Score | From Baseline to Week 8 | The Sheehan Disability Scale (SDS) is a 3-item clinician-rated questionnaire used to evaluate impairments in the domains of work, social life/leisure, and family life/home responsibility. All items are rated on an 11-point continuum (0 = no impairment to 10 = most severe) with the total SDS score ranging from 0 (no impairment) to 30 (most severe) |
Countries
United States
Participant flow
Recruitment details
Patient were recruited over a 21-month period from December of 2009 to September of 2011 at 23 studies sites in the United States.
Pre-assignment details
Patients went through a 1-week single-blind placebo run-in period immediately preceding an 8-week double-blind treatment period.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matching placebo capsules, oral administration, once daily dosing for 8 weeks. | 217 |
| Levomilnacipran ER Levomilnacipran ER capsules, flexible dose, oral administration, once daily dosing for 8 weeks. | 217 |
| Total | 434 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 7 | 17 |
| Overall Study | Lack of Efficacy | 4 | 4 |
| Overall Study | Lost to Follow-up | 14 | 16 |
| Overall Study | Other reasons | 1 | 2 |
| Overall Study | Protocol Violation | 10 | 7 |
| Overall Study | Withdrawal by Subject | 9 | 8 |
Baseline characteristics
| Characteristic | Placebo | Levomilnacipran ER | Total |
|---|---|---|---|
| Age Continuous | 44.6 years STANDARD_DEVIATION 13.9 | 45.0 years STANDARD_DEVIATION 13.2 | 44.8 years STANDARD_DEVIATION 13.5 |
| Age, Customized 18 years to 19 years | 2 participants | 2 participants | 4 participants |
| Age, Customized 20 years to 29 years | 38 participants | 34 participants | 72 participants |
| Age, Customized 30 years to 39 years | 37 participants | 44 participants | 81 participants |
| Age, Customized 40 years to 49 years | 51 participants | 40 participants | 91 participants |
| Age, Customized 50 years to 59 years | 57 participants | 68 participants | 125 participants |
| Age, Customized 60 years to 80 years | 32 participants | 29 participants | 61 participants |
| Body Mass Index (BMI) | 29.60 Kilograms Per Meter Squared STANDARD_DEVIATION 5.3 | 29.20 Kilograms Per Meter Squared STANDARD_DEVIATION 5.45 | 29.40 Kilograms Per Meter Squared STANDARD_DEVIATION 5.37 |
| Race/Ethnicity, Customized American Indian or Alaska native | 1 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized Asian | 2 participants | 2 participants | 4 participants |
| Race/Ethnicity, Customized Black or African American | 28 participants | 33 participants | 61 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 17 participants | 21 participants | 38 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 200 participants | 196 participants | 396 participants |
| Race/Ethnicity, Customized Other | 4 participants | 4 participants | 8 participants |
| Race/Ethnicity, Customized White | 182 participants | 177 participants | 359 participants |
| Region of Enrollment United States | 217 participants | 217 participants | 434 participants |
| Sex: Female, Male Female | 143 Participants | 140 Participants | 283 Participants |
| Sex: Female, Male Male | 74 Participants | 77 Participants | 151 Participants |
| Weight | 84.58 kg STANDARD_DEVIATION 18.15 | 84.47 kg STANDARD_DEVIATION 18.98 | 84.52 kg STANDARD_DEVIATION 18.55 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 79 / 217 | 151 / 217 |
| serious Total, serious adverse events | 3 / 217 | 4 / 217 |
Outcome results
Primary
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
MADRS was used to assess depressive symptomatology during the past week. Patients are 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 of the 10 items are scored on a 7-point scale. A score of 0 indicates the absence of symptoms,and a score of 6 indicates symptoms of maximum severity. The total MADRS score for this measure ranges from 0 (absence of symptoms) to 60 (maximum severity).
Time frame: From Baseline to Week 8
Population: The Safety Population consisted of 434 randomized patients who took at least 1 dose of double-blind investigational product. The Intent-to-Treat (ITT) Population consisted 429 patients in the Safety Population who had at least 1 postbaseline assessment of the MADRS total score.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | -12.2 units on a scale | Standard Error 0.78 |
| Levomilnacipran ER | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | -15.3 units on a scale | Standard Error 0.79 |
p-value: 0.005195% CI: [-5.256, -0.935]Mixed Models Analysis
Secondary
Change in Sheehan Disability Scale (SDS) Total Score
The Sheehan Disability Scale (SDS) is a 3-item clinician-rated questionnaire used to evaluate impairments in the domains of work, social life/leisure, and family life/home responsibility. All items are rated on an 11-point continuum (0 = no impairment to 10 = most severe) with the total SDS score ranging from 0 (no impairment) to 30 (most severe)
Time frame: From Baseline to Week 8
Population: The Safety Population consisted of 434 randomized patients who took at least 1 dose of double-blind investigational product.~The Intent-to-Treat (ITT) Population consisted 429 patients in the Safety Population who had at least 1 postbaseline assessment of the MADRS total score.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Sheehan Disability Scale (SDS) Total Score | -5.4 units on a scale | Standard Error 0.57 |
| Levomilnacipran ER | Change in Sheehan Disability Scale (SDS) Total Score | -8.0 units on a scale | Standard Error 0.58 |
p-value: 0.00195% CI: [-4.193, -1.07]Mixed Models Analysis