A Study of Duloxetine in Major Depressive Disorder (MDD) and Associated Painful Symptoms

Study Overview
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Brief Summary
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The purpose of this study is to find out if 60 mg of duloxetine given once a day by mouth for 8 weeks to patients diagnosed with major depressive disorder, who also report associated painful physical symptoms, is better than placebo when treating depression and its associated painful symptoms.

Official Title
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A Phase 4, 8-Week, Double-Blind, Randomized, Placebo-Controlled Study Evaluating the Efficacy of Duloxetine 60 mg Once Daily in Outpatients With Major Depressive Disorder and Associated Painful Physical Symptoms

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: Duloxetine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meets criteria for Major Depressive Disorder (MDD) as defined by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) and confirmed by Mini International Neuropsychiatric Interview (MINI) Montgomery-Asberg Depression Rating Scale (MADRS) total score of greater than or equal to 20 during the Screening Phase At least 1 previous episode of depression Painful physical symptoms with a score greater than or equal to 3 on the Brief Pain Inventory-Short Form (BPI-SF) average pain question during the Screening Phase A Clinical Global Impression of Severity (CGI-S) score of greater than or equal to 4 during the Screening Phase Written informed consent Exclusion Criteria: Currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an off-label use of an investigational drug or device Previously completed or withdrawn from this study or any other study investigating duloxetine Women of child-bearing potential who are not using a medically accepted means of contraception Any current (within the past 6 months) DSM-IV-TR primary Axis I diagnosis other than MDD History of alcohol abuse or dependence within 1 year immediately prior to being screened for the study Any prior history of bipolar disorder, psychosis, or schizophrenia Have an Axis II disorder that would interfere with study compliance Lack of a response of any (lifetime of subject) episode of major depression greater than or equal to 2 adequate courses of antidepressant therapy, defined as a clinically appropriate dose for a minimum of 4 weeks or, alternatively, in the judgment of the investigator, the subject meets criteria for treatment-resistant depression Have previously received treatment of MDD or Generalized Anxiety Disorder (GAD) with an adequate trial of duloxetine and did not respond or could not tolerate duloxetine Diagnosis of acute liver injury or severe cirrhosis Uncontrolled narrow-angle glaucoma Positive urine drug screen for any substance of abuse. A serious medical illness, including any cardiovascular, hepatic, renal, respiratory, hematologic, endocrinologic, or neurologic disease, or a clinically significant laboratory abnormality that is not stabilized or is anticipated to require intervention A history of substance abuse or dependence within 1 year before being screened for the study History of a serious suicide attempt or subject judged clinically to be at serious suicidal risk Require continuous use of opioid analgesics for 6 or more months because of chronic pain Pain of a known origin Meets criteria for fibromyalgia as defined by the American College of Rheumatology Experiences greater than or equal to 1 migraine headache per week Have had electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), or vagus nerve stimulation (VNS) within 1 year prior to being screened for the study Initiating, changing, or stopping psychotherapy within 6 weeks prior to being screened for the study or at any time during the study Investigator or subject anticipates initiating, changing, or stopping non-pharmacologic or alternative therapies for painful physical symptoms at any time during the study Are taking any excluded medications within 7 days prior to randomization with the exception of fluoxetine which cannot be taken within 30 days prior to randomization Treatment with a monoamine oxidase inhibitor (MAOI) within 14 days prior to randomization or have the potential need to use an MAOI during the study or within 5 days of discontinuing study drug Frequent and/or severe allergic reactions with multiple medications Abnormal thyroid stimulating hormone concentration Has epilepsy or history of seizure disorder or received treatment with anticonvulsant medication for epilepsy or seizures

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Duloxetine<br> | Drug: Duloxetine<br>* Participants received 30 mg duloxetine once daily (QD) by mouth (po) for 1 week followed by 60 mg QD, po for 7 weeks.<br>* Other names: Cymbalta;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Participants received placebo QD, po for 8 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Brief Pain Inventory-Short Form (BPI-SF) Average Pain Score During the 8-week Treatment Period | A self-reported scale that measures the severity of pain based on the average pain experienced over the past 24 hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). The overall change is based on the estimated main treatment effect. The Least Squares (LS) Mean Value was adjusted for treatment, investigator, visit, baseline, treatment*visit interaction, and baseline*visit interaction. | Day 1 through 8 weeks | 
| Change From Baseline in the Montgomery Asberg Depression Rating Scale (MADRS) Total Score at Week 8 | The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). The Least Squares (LS) Mean Value was adjusted for treatment, investigator, visit, baseline, treatment*visit interaction, and baseline*visit interaction. | Baseline, 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Sheehan Disability Scale (SDS) Total and Item Scores at Week 8 | SDS is completed by participant; used to assess effect of the participant's symptoms on their work/social/family life. Total scores range from 0 to 30; higher values indicate greater disruption in the participant's work/social/family life. Each item score ranges from 0 to 10 with higher values indicating greater disruption in the participant's work/school life (item 1), social life/leisure activities (item 2), or family life/home responsibilities (item 3). The LS Mean Value was adjusted for treatment, investigator, visit, baseline, treatment*visit interaction, and baseline*visit interaction. | Baseline, 8 weeks | 
| Change From Baseline in the Percentage of Participants Achieving Remission up to Week 8 | The Montgomery Asberg Depression Rating Scale (MADRS) is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). Remission is defined as achieving a MADRS total score ≤12. | Baseline, up to 8 weeks | 
| Percentage of Participants Achieving Remission up to Week 8 | The Montgomery Asberg Depression Rating Scale (MADRS) is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist. Items are rated on a scale from 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). Remission is defined as achieving a MADRS total score ≤12 at the last 2 nonmissing consecutive visits (for example, visit 3 [week 1] and visit 4 [week 2], or visit 4 [week 2] and visit 5 [week 4], or visit 5 [week 4] and visit 6 [week 8]). | Up to 8 weeks | 
| Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score at Week 4 | The MADRS is a rating scale for severity of depressive mood and symptoms. The MADRS has a 10-item checklist. Items are rated on a scale from 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). The Least Squares (LS) Mean Value was adjusted for treatment, investigator, visit, baseline, treatment*visit interaction, and baseline*visit interaction. | Baseline, 4 weeks | 
| Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score at Week 2 | The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range from 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). The Least Squares (LS) Mean Value was adjusted for treatment, investigator, visit, baseline, treatment*visit interaction, and baseline*visit interaction. | Baseline, 2 weeks | 
| Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 8 | Measures pain severity and interference on function. Severity scores: 0 (no pain) to 10 (severe pain) on each question. Interference scores: 0 (does not interfere) to 10 (completely interferes) on each question assessing interference of pain in past 24 hours for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. Average interference=average of nonmissing scores of individual interference items. LS Mean Value adjusted for treatment, investigator, visit, baseline, treatment*visit interaction, and baseline*visit interaction. | Baseline, 8 weeks | 
| Patient's Global Impressions of Improvement Scale (PGI-I) at Week 8 | A scale that measures the participant'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). The Least Squares (LS) Mean Value was adjusted for treatment, investigator, visit, and treatment*visit interaction. | 8 weeks | 
| Number of Participants With Suicidal Behaviors, Ideations, and Acts Based on the Columbia Suicide Severity Rating Scale (C-SSRS) During the Double-blind Treatment Phase | The C-SSRS captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Number of participants with suicidal behaviors, ideations, and acts are provided. Suicidal behavior: a yes answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, and completed suicide. Suicidal ideation: a yes answer to any 1 of 5 suicidal ideation questions, which includes wish to be dead, and 4 different categories of active suicidal ideation. Suicidal acts: a yes answer to actual attempt or completed suicide. | Baseline through 8 weeks | 
| Change From Baseline in Pulse Rate up to Week 8 | The change from baseline in pulse rate at week 8 is the primary analysis. For the primary analysis of pulse rate, the Least Squares (LS) Mean Value was adjusted for treatment, investigator, baseline, treatment*visit interaction, and baseline*visit interaction. The change from baseline in pulse rate up to week 8 is the secondary analysis. The LS Mean Value was adjusted for treatment, investigator, and baseline. | Baseline, up to week 8 | 
| Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Up to Week 8 | The change from baseline in SBP and DBP at week 8 is the primary analysis. For the primary analysis of SBP and DBP, the Least Squares (LS) Mean Value was adjusted for treatment, investigator, baseline, treatment*visit interaction, and baseline*visit interaction. The change from baseline in SBP and DBP up to week 8 is the secondary analysis. The LS Mean Value was adjusted for treatment, investigator, and baseline. | Baseline, up to week 8 | 
| Change From Baseline in Weight up to Week 8 | The change from baseline in weight at week 8 is the primary analysis. For the primary analysis of weight, the Least Squares (LS) Mean Value was adjusted for treatment, investigator, baseline, treatment*visit interaction, and baseline*visit interaction. The change from baseline in weight up to week 8 is the secondary analysis. The LS Mean Value was adjusted for treatment, investigator, and baseline. | Baseline, up to week 8 |