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

Phase 4

Completed

Conditions: Major Depressive Disorder

Interventions: Drug: Duloxetine
Drug: Placebo

Registration Number: NCT01000805

Lead Sponsor: Eli Lilly and Company

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 528

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Previously completed or withdrawn from this study or any other study investigating duloxetine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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Duloxetine	Duloxetine	-
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
Change From Baseline in the Brief Pain Inventory-Short Form (BPI-SF) Average Pain Score During the 8-week Treatment Period	Day 1 through 8 weeks	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.
Change From Baseline in the Montgomery Asberg Depression Rating Scale (MADRS) Total Score at Week 8	Baseline, 8 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in the Sheehan Disability Scale (SDS) Total and Item Scores at Week 8	Baseline, 8 weeks	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.
Change From Baseline in the Percentage of Participants Achieving Remission up to Week 8	Baseline, up to 8 weeks	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.
Percentage of Participants Achieving Remission up to Week 8	Up to 8 weeks	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 \[week 8\]).
Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score at Week 4	Baseline, 4 weeks	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.
Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score at Week 2	Baseline, 2 weeks	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.
Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 8	Baseline, 8 weeks	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.
Patient's Global Impressions of Improvement Scale (PGI-I) at Week 8	8 weeks	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.
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	Baseline through 8 weeks	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.
Change From Baseline in Pulse Rate up to Week 8	Baseline, 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.
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Up to Week 8	Baseline, 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.
Change From Baseline in Weight up to Week 8	Baseline, 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.

Trial Locations

Locations (1): For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
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Stockholm, Sweden