Duloxetine Versus Placebo in the Prevention of Recurrence of Major Depressive Disorder

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy and safety of duloxetine compared with placebo in the prevention of depressive recurrences among patients with recurrent major depressive disorder.

Official Title
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Duloxetine Versus Placebo in the Prevention of Recurrence of Major Depressive Disorder

Conditions
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Depressive Disorder, Major

Intervention / Treatment
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* Drug: Duloxetine
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient must be at least 18 years old. Patient must be diagnosed with depression and have had previous episodes of depression. Patient must sign informed consent. Exclusion Criteria: Female and pregnant or breastfeeding. History of bipolar disorder, schizophrenia, or other psychotic disorders. Suffer from a serious medical illness (other than depression) or abnormal laboratory result that would require a change in medication, intervention, or hospitalization. Have been treated with a medication called monoamine oxidase inhibitor (MAOI) within 14 days of the start of the study, or potential need to use a MAOI within 5 days of finishing the study. Have taken an antidepressant called fluoxetine within 30 days of the start of the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>duloxetine 60-120 mg every day (QD), by mouth (PO) for 34 weeks followed by duloxetine 60-120 mg QD, PO for up to 54 weeks | Drug: Duloxetine<br> <br> * Other names: Cymbalta;|
| Placebo Comparator: B<br>duloxetine 60-120 mg every day (QD), by mouth (PO) for 34 weeks followed by placebo QD, PO for up to 54 weeks | Drug: placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Depressive Recurrence After Time (t) in Days | Recurrence: Clinical Global Impression-Severity (CGI-S) score >=4 and met Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for major depressive disorder (MDD); had 3 consecutive visits where re-emergence criteria met; had total of 10 visits where re-emergence criteria was satisfied; discontinued due to lack of efficacy. | Every Visit from Week 34 up to Week 86 (Maintenance Phase) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence Count | Number of participants who experienced a depressive recurrence at any time during the double-blind maintenance therapy phase. | Every Visit from Week 35 up to Week 86 (Maintenance Phase) | 
| Percentage of Participants With Greater Than or Equal to 50% Worsening After Time (t) in Days | Worsening occurs if patient had a >=50% increase from baseline on the 17-Item Hamilton Depression Rating Scale (HAMD-17) total score and a Clinical Global Impression-Severity (CGI-S) score >=3 at any time during the double-blind maintenance therapy phase. | Every Visit from Week 34 up to Week 86 (Maintenance Phase) | 
| Loss of Response at Any Time | Loss of response was defined as a HAMD-17 total score >9 and a CGI-Severity score >2 at any one time during the double-blind maintenance phase of the study regardless of whether or not they subsequently regained response or not. | Every Visit from Week 35 up to Week 86 (Maintenance Phase) | 
| Change From Baseline to Endpoint in 17-Item Hamilton Depression Rating Scale (HAMD-17) Total Score - Acute and Continuation Phases | The 17-item HAMD measures depression severity. Each item was evaluated and scored using either a 5-point scale (e.g. absent, mild, moderate, severe, very severe) or a 3-point scale (e.g. absent, mild, marked). The total score of HAMD-17 may range from 0 (normal) to 52 (severe). | Week 0 and Week 10 (Acute) and Week 34 (Continuation) | 
| Change From Baseline to Endpoint in 17-Item Hamilton Depression Rating Scale (HAMD-17) Total Score - Maintenance Phase | The 17-item HAMD measures depression severity. Each item was evaluated and scored using either a 5-point scale (absent, mild, moderate, severe, very severe) or a 3-point scale (absent, mild, marked). The total score of HAMD-17 may range from 0 (normal) to 52 (severe). | Week 34 (baseline) and Week 86 (endpoint) (Maintenance Phase) | 
| Change From Baseline to Endpoint in Clinical Global Impressions (CGI) Severity Scale - Acute and Continuation Phases | Measures severity of illness at the time of assessment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). | Week 0 and Week 10 (Acute) and Week 34 (Continuation) | 
| Change From Baseline to Endpoint in Clinical Global Impressions (CGI) Severity Scale - Maintenance Phase | Measures severity of illness at the time of assessment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients. | Week 34 (baseline) and Week 86 (endpoint) (Maintenance Phase) | 
| Mean Values at Endpoint in Patient's Global Impressions of Improvement (PGI-I) - Acute and Continuation Phases | A scale that measures the patient's perception of improvement at the time of assessment compared with the start of treatment. The score ranges from 1 (very much better) to 7 (very much worse). | Week 10 (Acute) and Week 34 (Continuation) | 
| Mean Values at Endpoint in Patient's Global Impressions of Improvement (PGI-I) - Maintenance Phase | A scale that measures the patient's perception of improvement at the time of assessment compared with the start of treatment. The score ranges from 1 (very much better) to 7 (very much worse). | Week 86 (Maintenance Phase) | 
| Change From Baseline to Endpoint in Hamilton Depression Rating Scale Subscales, Including the Core, Maier, Anxiety/Somatization, Retardation/Somatization, and Sleep Subscales, and the Depressed Mood Item - Acute and Continuation Phases | Core and Maier subscales assess symptoms of depression (scores:0-20=Core; 0-24=Maier). Higher numbers indicate more severe symptoms. Anxiety/Somatization subscale assesses severity of anxiety (0-18). Retardation subscale assesses dysfunction in mood and work (0-14). Sleep subscale assesses insomnia (0-6). Depressed Mood Item (0-4). | Week 0 and Week 10 (Acute) and Week 34 (Continuation) | 
| Change From Baseline to Endpoint in Hamilton Depression Rating Scale Subscales, Including the Core, Maier, Anxiety/Somatization, Retardation/Somatization, and Sleep Subscales, and the Depressed Mood Item - Maintenance Phase | Core and Maier subscales assess symptoms of depression (scores:0-20=Core; 0-24=Maier). Higher numbers indicate more severe symptoms. Anxiety/Somatization subscale assesses severity of anxiety (0-18). Retardation subscale assesses dysfunction in mood and work (0-14). Sleep subscale assesses insomnia (0-6). Depressed Mood item (0-4). | Week 34 (baseline) and Week 86 (endpoint) (Maintenance Phase) | 
| Change From Baseline to Endpoint in Visual Analog Scales (VAS) for Pain - Acute and Continuation Phase | VAS for pain consists of 6 questions that assess overall pain, headache, back pain, shoulder pain, pain interference with daily activities, and pain while awake. Participant rates pain on a 100 millimeter (mm) line between two anchors (0 = no pain and 100 = very severe pain). | Week 0 and Week 10 (Acute) and Week 34 (Continuation) | 
| Change From Baseline to Endpoint in Visual Analog Scales (VAS) for Pain - Maintenance Phase | VAS for pain consists of 6 questions that assess overall pain, headache, back pain, shoulder pain, pain interference with daily activities, and pain while awake. Participant rates pain on a 100 millimeter (mm) line between two anchors (0 = no pain and 100 = very severe pain). | Week 34 (baseline) and Week 86 (endpoint) (Maintenance Phase) | 
| Change From Baseline to Endpoint in Symptom Questionnaire-Somatic Subscale (SQ-SS) - Acute and Continuation Phases | The Somatic subscale consists of 23 items to be completed by the patient that focus on somatic symptoms. Question answers are either yes/no or true/false. Negative response is scored at 1; positive response is scored as 0. Total Somatic subscale scores range from 0-23, where higher scores indicate greater symptom severity. | Week 0 and Week 10 (Acute) and Week 34 (Continuation) | 
| Change From Baseline to Endpoint in Symptom Questionnaire-Somatic Subscale (SQ-SS) - Maintenance Phase | The Somatic subscale consists of 23 items to be completed by the patient that focus on somatic symptoms. Question answers are either yes/no or true/false. Negative response is scored at 1; positive response is scored as 0. Total Somatic subscale scores range from 0-23, where higher scores indicate greater symptom severity. | Week 34 (baseline) and Week 86 (endpoint) (Maintenance Phase) | 
| Change From Baseline to Endpoint in Sheehan Disability Scale (SDS) - Acute and Continuation Phases | The SDS is completed by the patient and is used to assess the effect of the patient's symptoms on their work/social/family life. Total (Global) scores range from 0 to 30 with higher values indicating greater disruption in the patient's work/social/family life. Individual Item scores range from 0 to 10. | Week 0 and Week 10 (Acute) and Week 34 (Continuation) | 
| Change From Baseline to Endpoint in Sheehan Disability Scale (SDS) - Maintenance Phase | The SDS is completed by the patient and is used to assess the effect of the patient's symptoms on their work/social/family life. Total (Global) scores range from 0 to 30 with higher values indicating greater disruption in the patient's work/social/family life. Individual Item scores range from 0 to 10. | Week 34 (baseline) and Week 86 (endpoint) (Maintenance Phase) | 
| Change From Baseline to Endpoint in 36-item Short-Form Health Survey (SF-36) - Acute and Continuation Phase | Assesses general quality of life. 36 questions covering 8 health domains. Each subscale is scored by summing the individual items and transforming scores into a 0-100 scale, with higher scores indicating better health status or functioning. | Week 0 and Week 10 (Acute) and Week 34 (Continuation) | 
| Change From Baseline to Endpoint in 36-item Short-Form Health Survey (SF-36) - Maintenance Phase | Assesses general quality of life. 36 questions covering 8 health domains. Each subscale is scored by summing the individual items and transforming scores into a 0-100 scale, with higher scores indicating better health status or functioning. | Week 34 (baseline) and Week 86 (endpoint) (Maintenance Phase) | 
| Resource Utilization and Hospitalization Module - Visits to Health Care Providers - Acute and Continuation Phases | Measures direct and indirect costs. Direct costs include inpatient and outpatient costs, while indirect costs include lost days of work and caregiver time spent with patients. Patients self-report on number of days over the past month that they have been either late to work, missed work, or missed usual activities due to symptoms. | Week 0 through Week10 (Acute) through Week 34 (Continuation) | 
| Resource Utilization and Hospitalization Module - Visits to Health Care Providers - Maintenance Phase | Measures direct and indirect costs. Direct costs include inpatient and outpatient costs, while indirect costs include lost days of work and caregiver time spent with patients. Patients self-report on number of days over the past month that they have been either late to work, missed work, or missed usual activities due to symptoms. | Week 34 through Week 86 (Maintenance Phase) | 
| Resource Utilization and Hospitalization Module - Change From Baseline to Endpoint in Average Number of Hours Worked in a Week - Acute and Continuation Phases | Measures direct and indirect costs. Direct costs include inpatient and outpatient costs, while indirect costs include lost days of work and caregiver time spent with patients. Patients self-report on number of days over the past month that they have been either late to work, missed work, or missed usual activities due to symptoms. | Week 0 and Week 10 (Acute) and Week 34 (Continuation) | 
| Resource Utilization and Hospitalization Module - Change From Baseline to Endpoint in Average Number of Hours Worked in a Week - Maintenance Phase | Measures direct and indirect costs. Direct costs include inpatient and outpatient costs, while indirect costs include lost days of work and caregiver time spent with patients. Patients self-report on number of days over the past month that they have been either late to work, missed work, or missed usual activities due to symptoms. | Week 34 (baseline) and Week 86 (endpoint) (Maintenance Phase) | 
| Resource Utilization and Hospitalization Module - Change From Baseline to Endpoint in Number of Missed Paid Work Hours - Acute and Continuation Phase | Measures direct and indirect costs. Direct costs include inpatient and outpatient costs, while indirect costs include lost days of work and caregiver time spent with patients. Patients self-report on number of days over the past month that they have been either late to work, missed work, or missed usual activities due to symptoms. | Week 0 and Week 10 (Acute) and Week 34 (Continuation) | 
| Resource Utilization and Hospitalization Module - Change From Baseline to Endpoint in Number of Missed Paid Work Hours - Maintenance Phase | Measures direct and indirect costs. Direct costs include inpatient and outpatient costs, while indirect costs include lost days of work and caregiver time spent with patients. Patients self-report on number of days over the past month that they have been either late to work, missed work, or missed usual activities due to symptoms. | Week 34 (baseline) and Week 86 (endpoint) (Maintenance Phase) | 
| Change From Baseline to Endpoint in Arizona Sexual Experience Scale (ASEX) - Acute and Continuation Phases (Males) | A 5-item patient-rated scale measuring 5 domains: sexual drive, arousal (subjective excitement), lubrication/erection (physiological excitement), ability to reach orgasm, orgasm satisfaction. Higher score means worse dysfunction. Total score range is 5-30. | Week 0 and Week 10 (Acute) and Week 34 (Continuation) | 
| Change From Baseline to Endpoint in Arizona Sexual Experience Scale (ASEX) - Acute and Continuation Phases (Females) | A 5-item patient-rated scale measuring 5 domains: sexual drive, arousal (subjective excitement), lubrication/erection (physiological excitement), ability to reach orgasm, orgasm satisfaction. Higher score means worse dysfunction. Total score range is 5-30. | Week 0 and Week 10 (Acute) and Week 34 (Continuation) | 
| Change From Baseline to Endpoint in Arizona Sexual Experience Scale (ASEX) - Maintenance Phase (Males) | A 5-item patient-rated scale measuring 5 domains: sexual drive, arousal (subjective excitement), lubrication/erection (physiological excitement), ability to reach orgasm, orgasm satisfaction. Higher score means worse dysfunction. Total score range is 5-30. | Week 34 (baseline) and Week 86 (endpoint) (Maintenance Phase) | 
| Change From Baseline to Endpoint in Arizona Sexual Experience Scale (ASEX) - Maintenance Phase (Females) | A 5-item patient-rated scale measuring 5 domains: sexual drive, arousal (subjective excitement), lubrication/erection (physiological excitement), ability to reach orgasm, orgasm satisfaction. Higher score means worse dysfunction. Total score range is 5-30. | Week 34 (baseline) and Week 86 (endpoint) (Maintenance Phase) | 
| Vital Signs - Change From Baseline to Endpoint in Weight - Acute and Continuation Phases |  | Week 0 and Week 10 (Acute) and Week 34 (Continuation) | 
| Vital Signs - Change From Baseline to Endpoint in Weight - Maintenance Phase |  | Week 34 (baseline) and Week 86 (endpoint) (Maintenance Phase) | 
| Vital Signs - Change From Baseline to Endpoint in Pulse - Acute and Continuation Phases |  | Week 0 and Week 10 (Acute) and Week 34 (Continuation) | 
| Vital Signs - Change From Baseline to Endpoint in Pulse - Maintenance Phase |  | Week 34 (baseline) and Week 86 (endpoint) (Maintenance Phase) | 
| Vital Signs - Change From Baseline to Endpoint in Blood Pressure - Acute and Continuation Phases |  | Week 0 and Week 10 (Acute) and Week 34 (Continuation) | 
| Vital Signs - Change From Baseline to Endpoint in Blood Pressure - Maintenance Phase |  | Week 34 (baseline) and Week 86 (endpoint) (Maintenance Phase) | 
| Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Albumin - Acute Phase |  | Week 0 and Week 10 | 
| Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Calcium - Acute Phase |  | Week 0 and Week 10 | 
| Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Chloride - Acute Phase |  | Week 0 and Week 10 | 
| Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Eosinophils - Acute Phase |  | Week 0 and Week 10 | 
| Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Gamma-Glutamyl Transferase - Acute Phase |  | Week 0 and Week 10 | 
| Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Hematocrit - Acute Phase |  | Week 0 and Week 10 | 
| Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Hemoglobin - Acute Phase |  | Week 0 and Week 10 | 
| Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Platelet Count - Acute Phase |  | Week 0 and Week 10 | 
| Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Sodium - Acute Phase |  | Week 0 and Week 10 | 
| Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Total Protein - Acute Phase |  | Week 0 and Week 10 | 
| Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Uric Acid - Acute Phase |  | Week 0 and Week 10 | 
| Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Albumin - Continuation Phase |  | Week 10 (baseline) and Week 34 (endpoint) (Continuation Phase) | 
| Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Bicarbonate, HCO3 - Continuation Phase |  | Week 10 (baseline) and Week 34 (endpoint) (Continuation Phase) | 
| Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Bilirubin, Direct - Continuation Phase |  | Week 10 (baseline) and Week 34 (endpoint) (Continuation Phase) | 
| Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Bilirubin, Total - Continuation Phase |  | Week 10 (baseline) and Week 34 (endpoint) (Continuation Phase) | 
| Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Calcium - Continuation Phase |  | Week 10 (baseline) and Week 34 (endpoint) (Continuation Phase) | 
| Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Erythrocyte Count - Continuation Phase |  | Week 10 (baseline) and Week 34 (endpoint) (Continuation Phase) | 
| Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Gamma-Glutamyl Transferase - Continuation Phase |  | Week 10 (baseline) and Week 34 (endpoint) (Continuation Phase) | 
| Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Hematocrit - Continuation Phase |  | Week 10 (baseline) and Week 34 (endpoint) (Continuation Phase) | 
| Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Hemoglobin - Continuation Phase |  | Week 10 (baseline) and Week 34 (endpoint) (Continuation Phase) | 
| Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Leukocyte Count - Continuation Phase |  | Week 10 (baseline) and Week 34 (endpoint) (Continuation Phase) | 
| Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Low Density Lipoprotein (LDL) Cholesterol (Direct) - Continuation Phase |  | Week 10 (baseline) and Week 34 (endpoint) (Continuation Phase) | 
| Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Mean Cell Hemoglobin - Continuation Phase |  | Week 10 (baseline) and Week 34 (endpoint) (Continuation Phase) | 
| Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Mean Cell Volume (MCV) - Continuation Phase |  | Week 10 (baseline) and Week 34 (endpoint) (Continuation Phase) | 
| Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Monocytes - Continuation Phase |  | Week 10 (baseline) and Week 34 (endpoint) (Continuation Phase) | 
| Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Total Protein - Continuation Phase |  | Week 10 (baseline) and Week 34 (endpoint) (Continuation Phase) | 
| Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Alanine Aminotransferase (ALT) - Maintenance Phase |  | Week 34 (baseline) and Week 86 (endpoint) (Maintenance Phase) | 
| Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Calcium - Maintenance Phase |  | Week 34 (baseline) and Week 86 (endpoint) (Maintenance Phase) | 
| Statistically Significant Laboratory Measurements - Change From Baseline to Endpoint in Glucose - Maintenance Phase |  | Week 34 (baseline) and Week 86 (endpoint) (Maintenance Phase) | 
| Treatment-Emergent Adverse Events Occurring in at Least 5 Percent of Participants -- Open-Label Acute Therapy Phase |  | Every Visit from Week 0 up to Week 10 (Acute) | 
| Treatment-Emergent Adverse Events Occurring in at Least 5 Percent of the Participants -- Open-Label Continuation Phase |  | Every Visit from Week 10 up to Week 34 (Continuation) |