Depressive Disorder, Major
Conditions
Keywords
Fetzima, Relapse-prevention, Placebo-controlled
Brief summary
This study evaluates the efficacy, safety and tolerability of levomilnacipran extended-release (ER) compared with placebo in the prevention of depression relapse in major depressive disorder (MDD).
Interventions
Levomilnacipran ER taken orally at 40, 80 or 120 mg once daily.
DRUGPlacebo
Dose-matched placebo taken orally 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 70 Years
Healthy volunteers
No
Inclusion criteria
* Currently meet the DMS-5 (Diagnostic and Statistical Manual of Mental Disorders, 5th edition) criteria for Major Depressive Disorder (MDD) * The participant must have an ongoing major depressive episode of at least 8 weeks and no more than 18 months * The participant must have at least 3 lifetime episodes of MDD (including the current episode)
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 * Participants who are considered a suicide risk * History of non-response to 2 or more antidepressants (after adequate treatment) * Participants who have a history of meeting DMS-5 criteria for manic, hypomanic, or mixed episode, obsessive-compulsive disorder, schizophrenia or other psychotic disorder * Panic disorder
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Relapse During the Double-Blind Treatment Period (DBTP) | From the randomization date (Week 20) to the relapse date during the 26-week DBTP (up to Week 46) | Time to relapse for the median was measured in days from randomization date at the start of the DBTP to relapse date during DBTP. Relapse was defined as meeting any 1 or more of the following criteria: 1) Insufficient therapeutic response at any one visit, including a \>/= 2 increase in Clinical Global Impressions-Severity (CGI-S) score (range 1 to 7) compared with that obtained at randomization, or risk of suicide as determined by the investigator, or need for hospitalization due to worsening of depression as determined by the investigator, or need for alternative treatment of depressive symptoms as determined by the Investigator; 2) Montgomery-Asberg Depression Rating Scale (MADRS) total score \>/= 18 (range 0 to 60) at 2 consecutive visits (second visit within 7 to 14 days after the first visit at which the MADRS total score was ≥ 18). Participant was considered censored at the last visit during DBTP if participant did not meet the relapse criteria during DBTP. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Open-Label FETZIMA® FETZIMA® (levomilnacipran extended release \[ER\]) taken orally during flexible dose titration up to 40, 80 or 120 mg once daily in 8-week run-in period followed by fixed dose of 40, 80 or 120 mg once daily in 12-week stabilization period. | 644 |
| Total | 644 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double-blind Treatment Period | Adverse Event | 0 | 2 | 5 |
| Double-blind Treatment Period | Lost to Follow-up | 0 | 4 | 5 |
| Double-blind Treatment Period | Multiple Reasons | 0 | 8 | 2 |
| Double-blind Treatment Period | Non-Compliance With Study Drug | 0 | 1 | 4 |
| Double-blind Treatment Period | Protocol Violation | 0 | 1 | 2 |
| Double-blind Treatment Period | Withdrawal of Consent | 0 | 8 | 8 |
| Run-in Period | Adverse Event | 48 | 0 | 0 |
| Run-in Period | Lack of Efficacy | 16 | 0 | 0 |
| Run-in Period | Lost to Follow-up | 25 | 0 | 0 |
| Run-in Period | Non-Compliance With Study Drug | 3 | 0 | 0 |
| Run-in Period | Protocol Violation | 17 | 0 | 0 |
| Run-in Period | Reason not Specified | 8 | 0 | 0 |
| Run-in Period | Withdrawal of Consent | 28 | 0 | 0 |
| Stabilization Period | Adverse Event | 13 | 0 | 0 |
| Stabilization Period | Lack of Efficacy | 22 | 0 | 0 |
| Stabilization Period | Lost to Follow-up | 12 | 0 | 0 |
| Stabilization Period | Non-Compliance With Study Drug | 5 | 0 | 0 |
| Stabilization Period | Protocol Violation | 8 | 0 | 0 |
| Stabilization Period | Reason not Specified | 15 | 0 | 0 |
| Stabilization Period | Withdrawal of Consent | 23 | 0 | 0 |
Baseline characteristics
| Characteristic | Open-Label FETZIMA® |
|---|---|
| Age, Continuous | 43.1 years STANDARD_DEVIATION 13.9 |
| Sex: Female, Male Female | 404 Participants |
| Sex: Female, Male Male | 240 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 644 | 0 / 159 | 0 / 165 |
| other Total, other adverse events | 430 / 644 | 29 / 159 | 41 / 165 |
| serious Total, serious adverse events | 9 / 644 | 1 / 159 | 2 / 165 |
Outcome results
Primary
Time to First Relapse During the Double-Blind Treatment Period (DBTP)
Time to relapse for the median was measured in days from randomization date at the start of the DBTP to relapse date during DBTP. Relapse was defined as meeting any 1 or more of the following criteria: 1) Insufficient therapeutic response at any one visit, including a \>/= 2 increase in Clinical Global Impressions-Severity (CGI-S) score (range 1 to 7) compared with that obtained at randomization, or risk of suicide as determined by the investigator, or need for hospitalization due to worsening of depression as determined by the investigator, or need for alternative treatment of depressive symptoms as determined by the Investigator; 2) Montgomery-Asberg Depression Rating Scale (MADRS) total score \>/= 18 (range 0 to 60) at 2 consecutive visits (second visit within 7 to 14 days after the first visit at which the MADRS total score was ≥ 18). Participant was considered censored at the last visit during DBTP if participant did not meet the relapse criteria during DBTP.
Time frame: From the randomization date (Week 20) to the relapse date during the 26-week DBTP (up to Week 46)
Population: Double-blind Intent-to-Treat (ITT) population comprised of all participants in the Double-blind Safety Population who had at least 1 post-randomization assessment of MADRS or those participants who met relapse criteria during the DBTP of the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Double-Blind Placebo | Time to First Relapse During the Double-Blind Treatment Period (DBTP) | NA days |
| Double-Blind FETZIMA® | Time to First Relapse During the Double-Blind Treatment Period (DBTP) | NA days |
p-value: 0.021295% CI: [0.33, 0.92]Log Rank