Depression, Major Depressive Disorder
Conditions
Brief summary
The purpose of this study is to evaluate the safety and efficacy of Levomilnacipran ER relative to placebo in the prevention of depression relapse in patients with major depressive disorder (MDD).
Detailed description
Patients who demonstrate improvement in depressive symptoms at the end of the initial 12-week open-label treatment period with Levomilnacipran ER are randomized to continue Levomilnacipran ER or switch to placebo under double-blind conditions for up to 24 weeks of additional treatment.
Interventions
Drug: Levomilnacipran ER (40, 80 or 120 mg/day) Study drug is to be given orally, in capsule form, once daily.
DRUGPlacebo
Matching placebo to be given orally, in capsule form, once daily.
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 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: * 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 |
|---|---|---|
| Time to Relapse (Days) | 24 Weeks | Number of days until patients meet relapse criteria. Relapse was defined as 1 or more of the following: 1. MADRS total score of at least 22 at 2 consecutive visits 2. Increase of 2 or more points in CGI-I score compared with the CGI-I score at Visit 9 at 2 consecutive visits 3. Premature discontinuation due to insufficient therapeutic response 4. MADRS item 10 score of at least 4 |
Countries
Canada, United States
Participant flow
Recruitment details
Patient were recruited over a 10-month period from March of 2010 to January of 2011 at 36 studies sites, 30 in the United States and 6 in Canada.
Pre-assignment details
Patients began with a 12-week open-label treatment period, followed by a 24-week double-blind treatment period.
Participants by arm
| Arm | Count |
|---|---|
| Open Label Levomilnacipran ER 40, 80 or 120 mg Levomilnacipran ER capsules, oral administration, once daily dosing. | 734 |
| Total | 734 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-blind Intent-to-treat Population | Adverse Event | 3 | 8 |
| Double-blind Intent-to-treat Population | Lost to Follow-up | 4 | 17 |
| Double-blind Intent-to-treat Population | Positive serum pregnancy test result | 0 | 2 |
| Double-blind Intent-to-treat Population | Protocol Violation | 2 | 7 |
| Double-blind Intent-to-treat Population | Withdrawal by Subject | 11 | 22 |
| Double-Blind Period | Adverse Event | 3 | 8 |
| Double-Blind Period | Lost to Follow-up | 5 | 17 |
| Double-Blind Period | Other Reasons | 0 | 2 |
| Double-Blind Period | Protocol Violation | 2 | 7 |
| Double-Blind Period | Withdrawal by Subject | 11 | 24 |
| Open-Label Period | Adverse Event | 0 | 80 |
| Open-Label Period | Lack of Efficacy | 0 | 26 |
| Open-Label Period | Lost to Follow-up | 0 | 42 |
| Open-Label Period | Protocol Violation | 0 | 39 |
| Open-Label Period | Withdrawal by Subject | 0 | 53 |
Baseline characteristics
| Characteristic | Open Label Levomilnacipran ER |
|---|---|
| Age, Continuous | 42.2 years STANDARD_DEVIATION 12.3 |
| Age, Customized 18 years to 19 years | 8 Participants |
| Age, Customized 20 years to 29 years | 151 Participants |
| Age, Customized 30 years to 39 years | 127 Participants |
| Age, Customized 40 years to 49 years | 208 Participants |
| Age, Customized 50 years to 59 years | 186 Participants |
| Age, Customized 60 years to 65 years | 54 Participants |
| Body Mass Index (BMI) | 28.88 Kilograms Per Meter Squared STANDARD_DEVIATION 5.42 |
| Region of Enrollment Canada | 51 Participants |
| Region of Enrollment United States | 683 Participants |
| Sex: Female, Male Female | 425 Participants |
| Sex: Female, Male Male | 309 Participants |
| Weight | 83.41 kg STANDARD_DEVIATION 18.43 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 734 | 0 / 112 | 0 / 233 |
| other Total, other adverse events | 448 / 734 | 31 / 112 | 68 / 233 |
| serious Total, serious adverse events | 7 / 734 | 4 / 112 | 2 / 233 |
Outcome results
Primary
Time to Relapse (Days)
Number of days until patients meet relapse criteria. Relapse was defined as 1 or more of the following: 1. MADRS total score of at least 22 at 2 consecutive visits 2. Increase of 2 or more points in CGI-I score compared with the CGI-I score at Visit 9 at 2 consecutive visits 3. Premature discontinuation due to insufficient therapeutic response 4. MADRS item 10 score of at least 4
Time frame: 24 Weeks
Population: The double blind Intent-to-treat population consists of 342 randomized participants who received study drug and were evaluated for the Primary Outcome Measure
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Time to Relapse (Days) | NA Days |
| Levomilnacipran ER | Time to Relapse (Days) | NA Days |