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 compared to placebo in patients with Major Depressive Disorder (MDD).
Interventions
Drug: Levomilnacipran ER 40mg/day 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 75 Years
Healthy volunteers
No
Inclusion criteria
* Men and women, 18-75 years old * Currently meet the DSM-IV-TR criteria for Major Depressive Disorder * The patient's current depressive episode must be at least 6 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 who are considered a suicide risk * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score - Mixed-effects Model for Repeated Measures (MMRM) Analysis. | From Baseline to Week 8 | The Montgomery-Asberg Depression Rating Scale (MADRS) rates patients 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. A score of 0 indicated the absence of symptoms, and a score of 6 indicated symptoms of maximum severity. The minimum overall score possible was 0 (absence of symptoms), with a maximum overall score of 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
Canada, United States
Participant flow
Recruitment details
Patient recruitment occurred during a 6 month period from June to December 2011 at 47 study sites in the United States and 4 study sites in Canada.
Pre-assignment details
All patients went through a 1-week single-blind placebo run-in period before randomization.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Dose matched placebo, oral administration in capsule form, once daily for 8 weeks. | 186 |
| Levomilnacipran ER 40 mg 40mg Levomilnacipran ER, oral administration in capsule form, once daily for 8 weeks. | 188 |
| Levomilnacipran 80 mg 40mg Levomilnacipran ER, oral administration in capsule form, once daily for 8 weeks. | 188 |
| Total | 562 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 12 | 19 |
| Overall Study | Lack of Efficacy | 3 | 3 | 3 |
| Overall Study | Lost to Follow-up | 14 | 8 | 11 |
| Overall Study | Protocol Violation | 4 | 10 | 6 |
| Overall Study | Withdrawal by Subject | 8 | 10 | 7 |
Baseline characteristics
| Characteristic | Total | Levomilnacipran 80 mg | Placebo | Levomilnacipran ER 40 mg |
|---|---|---|---|---|
| Age Continuous | 42.8 years STANDARD_DEVIATION 13.1 | 43.1 years STANDARD_DEVIATION 12.8 | 42.3 years STANDARD_DEVIATION 13.2 | 42.9 years STANDARD_DEVIATION 13.4 |
| Age, Customized < 20 | 9 participants | 5 participants | 3 participants | 1 participants |
| Age, Customized ≥ 20-29 | 98 participants | 28 participants | 35 participants | 35 participants |
| Age, Customized ≥ 30-39 | 127 participants | 44 participants | 43 participants | 40 participants |
| Age, Customized ≥ 40-49 | 147 participants | 53 participants | 45 participants | 49 participants |
| Age, Customized ≥ 50-59 | 121 participants | 36 participants | 43 participants | 42 participants |
| Age, Customized ≥ 60 | 60 participants | 22 participants | 17 participants | 21 participants |
| Body Mass Index (BMI) | 28.54 Kilograms Per Meter Squared STANDARD_DEVIATION 5.35 | 28.71 Kilograms Per Meter Squared STANDARD_DEVIATION 5.68 | 28.67 Kilograms Per Meter Squared STANDARD_DEVIATION 5.19 | 28.25 Kilograms Per Meter Squared STANDARD_DEVIATION 5.17 |
| Height | 168.84 cm STANDARD_DEVIATION 9.47 | 168.63 cm STANDARD_DEVIATION 8.91 | 168.41 cm STANDARD_DEVIATION 9.69 | 169.48 cm STANDARD_DEVIATION 9.79 |
| Race/Ethnicity, Customized American Indian of Alaska Native | 3 participants | 0 participants | 3 participants | 0 participants |
| Race/Ethnicity, Customized Asian | 14 participants | 3 participants | 7 participants | 4 participants |
| Race/Ethnicity, Customized Black or African-American | 108 participants | 36 participants | 35 participants | 37 participants |
| Race/Ethnicity, Customized Hispanic | 62 participants | 15 participants | 23 participants | 24 participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 1 participants | 0 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Non-Hispanic | 500 participants | 173 participants | 163 participants | 164 participants |
| Race/Ethnicity, Customized Other Race | 20 participants | 10 participants | 5 participants | 5 participants |
| Race/Ethnicity, Customized White | 416 participants | 139 participants | 135 participants | 142 participants |
| Region of Enrollment Canada | 22 participants | 8 participants | 9 participants | 5 participants |
| Region of Enrollment United States | 540 participants | 180 participants | 177 participants | 183 participants |
| Sex: Female, Male Female | 357 Participants | 124 Participants | 116 Participants | 117 Participants |
| Sex: Female, Male Male | 205 Participants | 64 Participants | 70 Participants | 71 Participants |
| Weight | 81.56 kg STANDARD_DEVIATION 17.45 | 81.73 kg STANDARD_DEVIATION 17.57 | 81.60 kg STANDARD_DEVIATION 17.77 | 81.35 kg STANDARD_DEVIATION 17.09 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 58 / 186 | 90 / 188 | 110 / 188 |
| serious Total, serious adverse events | 1 / 186 | 3 / 188 | 0 / 188 |
Outcome results
Primary
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score - Mixed-effects Model for Repeated Measures (MMRM) Analysis.
The Montgomery-Asberg Depression Rating Scale (MADRS) rates patients 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. A score of 0 indicated the absence of symptoms, and a score of 6 indicated symptoms of maximum severity. The minimum overall score possible was 0 (absence of symptoms), with a maximum overall score of 60 (maximum severity).
Time frame: From Baseline to Week 8
Population: Of the 568 patients randomized to receive double-blind treatment, 562 patients received at least 1 dose of treatment and were included in the Safety Population, and 557 patients received at least 1 dose of treatment and had at least 1 postbaseline MADRS assessment and were included in the ITT Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score - Mixed-effects Model for Repeated Measures (MMRM) Analysis. | -11.3 Units on a scale | Standard Deviation 0.77 |
| Levomilnacipran ER 40 mg | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score - Mixed-effects Model for Repeated Measures (MMRM) Analysis. | -14.6 Units on a scale | Standard Deviation 0.79 |
| Levomilnacipran ER 80 mg | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score - Mixed-effects Model for Repeated Measures (MMRM) Analysis. | -14.4 Units on a scale | Standard Deviation 0.79 |
p-value: 0.002795% CI: [-5.457, -1.148]mixed-model for repeated measures
p-value: 0.004395% CI: [-5.293, -0.988]mixed-model for repeated measures
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: Of the 568 patients randomized to receive double-blind treatment, 562 patients received at least 1 dose of treatment and were included in the Safety Population, and 557 patients received at least 1 dose of treatment and had at least 1 postbaseline MADRS assessment and were included in the ITT Population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Sheehan Disability Scale (SDS) Total Score | -5.4 units on a scale | Standard Error 0.66 |
| Levomilnacipran ER 40 mg | Change in Sheehan Disability Scale (SDS) Total Score | -7.3 units on a scale | Standard Error 0.68 |
| Levomilnacipran ER 80 mg | Change in Sheehan Disability Scale (SDS) Total Score | -8.2 units on a scale | Standard Error 0.66 |
p-value: 0.045995% CI: [-3.62, -0.033]Mixed Models Analysis
p-value: 0.002895% CI: [-4.494, -0.946]Mixed Models Analysis