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 fixed doses versus placebo in the treatment of outpatients with major depressive disorder.
Interventions
Levomilnacipran ER, 40 mg, oral administration, in capsule form, once daily for 8 weeks.
DRUGPlacebo
Matching placebo capsules, oral administration, 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 65 Years
Healthy volunteers
No
Inclusion criteria
* Men and women, 18-65 years old * Currently meet the DSM-IV-TR criteria for Major Depressive Disorder * The patient's current depressive episode must be at least 8 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: * any manic or hypomanic episode * schizophrenia or any other psychotic disorder * obsessive-compulsive disorder * Patients who are considered a suicide risk
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score | From Baseline to Week 8 | The 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 for all measured symptoms). |
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 functional 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 for all measured symptoms) |
Countries
United States
Participant flow
Recruitment details
Patient recruitment at 38 study centers located in the United States during a 17 month period from September 2009 to February 2011.
Pre-assignment details
The study included a 1-week, single-blind placebo run-in period immediately before the 8-week double-blind treatment period.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Dose matching placebo capsules, oral administration, once daily dosing for 8 weeks | 176 |
| Levomilnacipran ER 40 mg 40 mg per day Levomilnacipran ER capsules, oral administration, once daily for 8 weeks. | 178 |
| Levomilnacipran ER 80 mg 80 mg per day Levomilnacipran ER capsules, oral administration, once daily for 8 weeks. | 179 |
| Levomilnacipran ER 120 mg 120 mg per day Levomilnacipran ER capsules, oral administration, once daily for 8 weeks. | 180 |
| Total | 713 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 13 | 26 | 12 |
| Overall Study | Lack of Efficacy | 7 | 4 | 1 | 3 |
| Overall Study | Lost to Follow-up | 10 | 14 | 8 | 15 |
| Overall Study | Other reasons | 0 | 0 | 3 | 0 |
| Overall Study | Protocol Violation | 9 | 5 | 9 | 10 |
| Overall Study | Withdrawal by Subject | 9 | 12 | 11 | 23 |
Baseline characteristics
| Characteristic | Placebo | Levomilnacipran ER 40 mg | Levomilnacipran ER 80 mg | Levomilnacipran ER 120 mg | Total |
|---|---|---|---|---|---|
| Age Continuous | 43.1 years STANDARD_DEVIATION 11.3 | 41.6 years STANDARD_DEVIATION 13.1 | 41.0 years STANDARD_DEVIATION 12.8 | 40.3 years STANDARD_DEVIATION 11.9 | 41.1 years STANDARD_DEVIATION 12.3 |
| Age, Customized 18 years to 19 years | 1 participants | 2 participants | 4 participants | 2 participants | 9 participants |
| Age, Customized 20 years to 29 years | 31 participants | 43 participants | 44 participants | 42 participants | 160 participants |
| Age, Customized 30 years to 39 years | 47 participants | 34 participants | 33 participants | 38 participants | 152 participants |
| Age, Customized 40 years to 49 years | 44 participants | 36 participants | 48 participants | 46 participants | 174 participants |
| Age, Customized 50 years to 59 years | 46 participants | 48 participants | 36 participants | 41 participants | 171 participants |
| Age, Customized 60 years to 65 years | 7 participants | 15 participants | 14 participants | 11 participants | 47 participants |
| Body Mass Index (BMI) | 29.0 Kilograms Per Meter Squared STANDARD_DEVIATION 5.8 | 28.0 Kilograms Per Meter Squared STANDARD_DEVIATION 5.3 | 28.9 Kilograms Per Meter Squared STANDARD_DEVIATION 5.4 | 29.2 Kilograms Per Meter Squared STANDARD_DEVIATION 5.4 | 28.8 Kilograms Per Meter Squared STANDARD_DEVIATION 5.5 |
| Race/Ethnicity, Customized American Indian or Alaska native | 1 participants | 0 participants | 2 participants | 1 participants | 4 participants |
| Race/Ethnicity, Customized Asian | 8 participants | 3 participants | 5 participants | 3 participants | 19 participants |
| Race/Ethnicity, Customized Black or African American | 29 participants | 36 participants | 39 participants | 41 participants | 145 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 20 participants | 22 participants | 28 participants | 22 participants | 92 participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 0 participants | 0 participants | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 156 participants | 155 participants | 151 participants | 158 participants | 620 participants |
| Race/Ethnicity, Customized Other | 3 participants | 6 participants | 4 participants | 4 participants | 17 participants |
| Race/Ethnicity, Customized White | 134 participants | 133 participants | 129 participants | 130 participants | 526 participants |
| Region of Enrollment United States | 176 participants | 178 participants | 179 participants | 180 participants | 713 participants |
| Sex: Female, Male Female | 108 Participants | 122 Participants | 111 Participants | 106 Participants | 447 Participants |
| Sex: Female, Male Male | 68 Participants | 56 Participants | 68 Participants | 74 Participants | 266 Participants |
| Weight | 83.8 kg STANDARD_DEVIATION 19.3 | 79.5 kg STANDARD_DEVIATION 17.1 | 83.0 kg STANDARD_DEVIATION 17.3 | 84.2 kg STANDARD_DEVIATION 18.6 | 82.6 kg STANDARD_DEVIATION 18.1 |
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 | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 66 / 176 | 110 / 178 | 122 / 179 | 112 / 180 |
| serious Total, serious adverse events | 1 / 176 | 3 / 178 | 2 / 179 | 1 / 180 |
Outcome results
Primary
Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score
The 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 for all measured symptoms).
Time frame: From Baseline to Week 8
Population: A total of 724 patients were randomized to receive double-blind treatment (Randomized Population); 713 patients received at least 1 dose of treatment (Safety Population); and 704 patients received at least 1 dose of treatment and had at least 1 postbaseline MADRS-CR assessment (Intent to Treat \[ITT\] Population).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score | -11.6 Units on a scale | Standard Error 0.97 |
| Levomilnacipran ER 40 mg | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score | -14.8 Units on a scale | Standard Error 0.99 |
| Levomilnacipran ER 80 mg | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score | -15.6 Units on a scale | Standard Error 1 |
| Levomilnacipran ER 120 mg | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score | -16.5 Units on a scale | Standard Error 1.02 |
p-value: 0.018695% CI: [-5.92, -0.54]Mixed Models Analysis
p-value: 0.003895% CI: [-6.69, -1.29]Mixed Models Analysis
p-value: 0.000595% CI: [-7.59, -2.12]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 functional 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 for all measured symptoms)
Time frame: From Baseline to Week 8
Population: A total of 724 patients were randomized to receive double-blind treatment (Randomized Population); 713 patients received at least 1 dose of treatment (Safety Population); and 704 patients received at least 1 dose of treatment and had at least 1 postbaseline MADRS-CR assessment(Intent to Treat \[ITT\] Population).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Sheehan Disability Scale (SDS) Total Score | -7.2 units on a scale | Standard Error 0.74 |
| Levomilnacipran ER 40 mg | Change in Sheehan Disability Scale (SDS) Total Score | -8.6 units on a scale | Standard Error 0.75 |
| Levomilnacipran ER 80 mg | Change in Sheehan Disability Scale (SDS) Total Score | -9.7 units on a scale | Standard Error 0.77 |
| Levomilnacipran ER 120 mg | Change in Sheehan Disability Scale (SDS) Total Score | -9.7 units on a scale | Standard Error 0.78 |
p-value: 0.168795% CI: [-3.42, 0.6]Mixed Models Analysis
p-value: 0.015195% CI: [-4.54, -0.49]Mixed Models Analysis
p-value: 0.014195% CI: [-4.62, -0.52]Mixed Models Analysis