Major Depressive Disorder
Conditions
Keywords
Depression, Fatigue, Major Depressive Disorder
Brief summary
The purpose of the study is to evaluate the efficacy, safety and tolerability of Levomilnacipran ER for the treatment of fatigue associated with major depressive disorder (MDD).
Interventions
Drug: Levomilnacipran ER (40 -120 mg/day) Study drug is to be given orally, in capsule form, once daily for 8 weeks
DRUGParoxetine, Sertraline, Citalopram or Fluoxetine.
Paroxetine (20, 40, or 60 mg/day) to be given orally, in capsule form, once daily for 8 weeks, or Sertraline (50, 100, or 150 mg/day) to be given orally, in capsule form, once daily for 8 weeks, or Citalopram (20, 40, or 60 mg/day) to be given orally, in capsule form, once daily for 8 weeks or Fluoxetine (20, 40, or 60 mg/day) to be given orally, in capsule form, once daily for 8 weeks
DRUGPlacebo
Matching placebo capsules, oral administration, once daily dosing
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 Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision (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 of child-bearing potential who are not practicing a reliable method of birth control * Patients with a history of meeting DSM-IV-TR criteria for: 1. any manic or hypomanic episode; 2. schizophrenia or any other psychotic disorder; 3. obsessive-compulsive disorder. * Patients who are considered a suicide risk
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Clinical Global Impression of Severity (CGI-S) for Fatigue Score | From Baseline to Week 8 | The CGI-S is a clinician-rated scale that rates the severity of the patient's current state of fatigue based on the Investigator's clinical opinion with regard to the patient population with Major Depressive Disorder (MDD). Patient were rated on a scale from 1 to 7, with 1 indicating a normal state and 7 indicating that the patient was among the most extremely fatigued |
| Change in Patient Global Impressions of Severity (PGI-S) for Fatigue Score | From Baseline to Week 8 | The PGI-S is a clinician-rated scale that rates was used to rate the severity of the patient's current state of overall fatigue. Patients were rated on a scale from 1 to 7, with 1 indicating no symptoms of fatigue and 7 indicating extreme fatigue. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Cognitive and Physical Functioning Questionnaire (CPFQ), Last Observation Carried Forward | From Baseline to Week 8 | The Cognitive and Physical Functioning Questionnaire is a patient-rated, 7-item scale used to measure cognitive and executive dysfunction in mood and anxiety disorders. The CPFQ is sensitive to change with treatment and displays convergent validity by significant correlations with other measures of sleepiness, fatigue, apathy, and neuropsychological functioning. Patients are rated on a scale from 1 to 6 for seven common complaints of depressed patients reporting fatigue or cognitive/executive problems-with 1 indicating greater than normal functioning, 2 indicating normal functioning, and 3 to 6 indicating degrees of impaired functioning. The CPFQ ranges from the best possible score of 7 (greater than normal functioning) to the worst possible score of 42 (totally absent). |
Countries
United States
Participant flow
Recruitment details
Patients were recruited over a 12-month period from April of 2011 to April of 2012 at 20 studies sites in the United States.
Pre-assignment details
Patients went through a 1-week single-blind placebo run-in period, followed by an 8-week double-blind treatment period.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matching placebo capsules, oral administration
Placebo : Matching placebo capsules, oral administration, once daily dosing | 89 |
| Levomilnacipran ER 40 - 120 mg Levomilnacipran ER capsules, oral administration, once daily for 8 weeks | 85 |
| SSRI Randomized to treatment with 1 of 4 Selective Serotonin Reuptake Inhibitors (SSRIs) - Paroxetine, Sertraline, Citalopram or Fluoxetine.
Paroxetine (20, 40, or 60 mg/day) to be given orally, in capsule form, once daily for 8 weeks, or Sertraline (50, 100, or 150 mg/day) to be given orally, in capsule form, once daily for 8 weeks, or Citalopram (20, 40, or 60 mg/day) to be given orally, in capsule form, once daily for 8 weeks or Fluoxetine (20, 40, or 60 mg/day) to be given orally, in capsule form, once daily for 8 weeks. | 77 |
| Total | 251 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 6 | 3 | 2 |
| Overall Study | Lack of Efficacy | 1 | 0 | 1 |
| Overall Study | Lost to Follow-up | 10 | 6 | 5 |
| Overall Study | Other Reasons | 0 | 0 | 2 |
| Overall Study | Protocol Violation | 1 | 7 | 3 |
| Overall Study | Withdrawal by Subject | 4 | 2 | 4 |
Baseline characteristics
| Characteristic | Levomilnacipran ER | Placebo | Total | SSRI |
|---|---|---|---|---|
| Age, Continuous | 42.9 years STANDARD_DEVIATION 12.6 | 41.4 years STANDARD_DEVIATION 12 | 42.3 years STANDARD_DEVIATION 12 | 42.8 years STANDARD_DEVIATION 11.3 |
| Body Mass Index (BMI) | 28.61 Kilograms Per Meter Squared STANDARD_DEVIATION 5.22 | 28.16 Kilograms Per Meter Squared STANDARD_DEVIATION 4.85 | 28.51 Kilograms Per Meter Squared STANDARD_DEVIATION 5.04 | 28.80 Kilograms Per Meter Squared STANDARD_DEVIATION 5.1 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 participants | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Asian | 3 participants | 1 participants | 6 participants | 2 participants |
| Race/Ethnicity, Customized Black or African American | 25 participants | 26 participants | 76 participants | 25 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 4 participants | 8 participants | 22 participants | 10 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 81 participants | 81 participants | 229 participants | 67 participants |
| Race/Ethnicity, Customized Other | 0 participants | 0 participants | 2 participants | 2 participants |
| Race/Ethnicity, Customized White | 57 participants | 62 participants | 166 participants | 47 participants |
| Region of Enrollment United States | 85 participants | 89 participants | 251 participants | 77 participants |
| Sex: Female, Male Female | 49 Participants | 58 Participants | 156 Participants | 49 Participants |
| Sex: Female, Male Male | 36 Participants | 31 Participants | 95 Participants | 28 Participants |
| Weight | 82.23 kg STANDARD_DEVIATION 18.14 | 79.95 kg STANDARD_DEVIATION 15.27 | 81.75 kg STANDARD_DEVIATION 17 | 83.31 kg STANDARD_DEVIATION 17.61 |
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 | 39 / 89 | 41 / 85 | 37 / 77 |
| serious Total, serious adverse events | 0 / 89 | 1 / 85 | 0 / 77 |
Outcome results
Primary
Change in Clinical Global Impression of Severity (CGI-S) for Fatigue Score
The CGI-S is a clinician-rated scale that rates the severity of the patient's current state of fatigue based on the Investigator's clinical opinion with regard to the patient population with Major Depressive Disorder (MDD). Patient were rated on a scale from 1 to 7, with 1 indicating a normal state and 7 indicating that the patient was among the most extremely fatigued
Time frame: From Baseline to Week 8
Population: The Randomized Population consisted of 262 patients, with 251 patients who took at least 1 dose of double-blind treatment to comprise the Safety population.~The Intent-to-Treat (ITT) Population consisted of 248 patients in the Safety Population who had a baseline and at least 1 postbaseline assessment of either the CGI-S or PGI-I fatigue score.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Clinical Global Impression of Severity (CGI-S) for Fatigue Score | -1.5 units on a scale | Standard Deviation 1.3 |
| Levomilnacipran ER | Change in Clinical Global Impression of Severity (CGI-S) for Fatigue Score | -1.8 units on a scale | Standard Deviation 1.4 |
| SSRI | Change in Clinical Global Impression of Severity (CGI-S) for Fatigue Score | -1.9 units on a scale | Standard Deviation 1.4 |
Primary
Change in Patient Global Impressions of Severity (PGI-S) for Fatigue Score
The PGI-S is a clinician-rated scale that rates was used to rate the severity of the patient's current state of overall fatigue. Patients were rated on a scale from 1 to 7, with 1 indicating no symptoms of fatigue and 7 indicating extreme fatigue.
Time frame: From Baseline to Week 8
Population: The Randomized Population consisted of 262 patients, with 251 patients who took at least 1 dose of double-blind treatment to comprise the Safety population.~The Intent-to-Treat (ITT) Population consisted of 248 patients in the Safety Population who had a baseline and at least 1 postbaseline assessment of either the CGI-S or PGI-I fatigue score.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Patient Global Impressions of Severity (PGI-S) for Fatigue Score | -1.4 units on a scale | Standard Deviation 1.5 |
| Levomilnacipran ER | Change in Patient Global Impressions of Severity (PGI-S) for Fatigue Score | -1.7 units on a scale | Standard Deviation 1.5 |
| SSRI | Change in Patient Global Impressions of Severity (PGI-S) for Fatigue Score | -1.7 units on a scale | Standard Deviation 1.5 |
Secondary
Change in Cognitive and Physical Functioning Questionnaire (CPFQ), Last Observation Carried Forward
The Cognitive and Physical Functioning Questionnaire is a patient-rated, 7-item scale used to measure cognitive and executive dysfunction in mood and anxiety disorders. The CPFQ is sensitive to change with treatment and displays convergent validity by significant correlations with other measures of sleepiness, fatigue, apathy, and neuropsychological functioning. Patients are rated on a scale from 1 to 6 for seven common complaints of depressed patients reporting fatigue or cognitive/executive problems-with 1 indicating greater than normal functioning, 2 indicating normal functioning, and 3 to 6 indicating degrees of impaired functioning. The CPFQ ranges from the best possible score of 7 (greater than normal functioning) to the worst possible score of 42 (totally absent).
Time frame: From Baseline to Week 8
Population: The Randomized Population consisted of 262 patients, with 251 patients who took at least 1 dose of double-blind treatment to comprise the Safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Cognitive and Physical Functioning Questionnaire (CPFQ), Last Observation Carried Forward | -5.9 units on a scale | Standard Deviation 7.9 |
| Levomilnacipran ER | Change in Cognitive and Physical Functioning Questionnaire (CPFQ), Last Observation Carried Forward | -7.0 units on a scale | Standard Deviation 7.3 |
| SSRI | Change in Cognitive and Physical Functioning Questionnaire (CPFQ), Last Observation Carried Forward | -6.4 units on a scale | Standard Deviation 7 |