Duloxetine Versus Placebo in Chronic Low Back Pain

Study Overview
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Brief Summary
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The primary purpose of your participation in this study is to help answer the following research question, and not to provide you treatment for your condition. Whether duloxetine once daily can help patients with Chronic Low Back Pain. Patients who do not have their pain reduced by at least 30% by week 7 will be given 120 mg dose for the duration of the study. After the 13 week double blind period, patients randomized to placebo will switch to duloxetine 60 mg or 120 mg in the 41-week extension period.

Official Title
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Effect of Duloxetine 60 mg to 120 mg Once Daily in Patients With Chronic Low Back Pain

Conditions
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Back Pain Without Radiation

Intervention / Treatment
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* Drug: Duloxetine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male/Female outpatients 18 years of age with chronic low back pain Females of child bearing potential must test negative on a pregnancy test at visit 1. Exclusion Criteria: Have a serious or unstable diseases of the heart or blood vessels, liver, kidney, lungs, or blood-related illness Problems with decreased blood flow to arms and legs (peripheral vascular disease), or other medical conditions Psychiatric conditions that, in the opinion of the investigator, would affect your participation or be likely to lead to hospitalization during the course of the study Have acute liver injury (such as hepatitis) or severe cirrhosis Have had previous exposure to duloxetine Have a body mass index (BMI) over 40 Have a major depressive disorder Require daily narcotics Have suicidal risk Have a presence of any factors/conditions, medical or other, that in the judgment of the investigator may interfere with performance of study outcome measures

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: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Duloxetine<br>30 mg, every day (QD), by mouth (PO) for 1 week followed by 60 mg, QD, PO, 6 weeks then 60 mg (responders) or 120 mg (non-responders), QD, PO, 6 weeks during the placebo-controlled phase, then 60 mg or 120 mg, QD, PO, 41 weeks during the extension phase | Drug: Duloxetine<br>* 30 mg, every day (QD), by mouth (PO) for 1 week followed by 60 mg, QD, PO, 6 weeks then 60 mg (responders) or 120 mg (non-responders), QD, PO, 6 weeks during the placebo-controlled phase, then 60 mg or 120 mg, QD, PO, 41 weeks during the extension phase<br>* Other names: Cymbalta;|
| Placebo Comparator: Placebo<br>every day (QD), by mouth (PO), 13 weeks | Drug: Placebo<br>* every day (QD), by mouth (PO), 13 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 13 in Brief Pain Inventory (BPI), 24-hour Average Pain Scores | A self-reported scale that measures the severity of pain based on the average pain over the past 24-hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). | Baseline, Week 13 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient's Global Impression of Improvement (PGI-I) | A scale that measures the patient's perception of improvement at the time of assessment. The score ranges from 1 (very much better) to 7 (very much worse). | Week 13 | 
| Change From Baseline to Week 13 and Week 54 Endpoints in Roland Morris Disability Questionnaire-24 Item (RMDQ-24) Total Score | Roland-Morris questionnaire will be completed by the patient and measures the degree of disability due to back pain. The questionnaire consists of 24 statements and the patient is instructed to put a mark next to each appropriate statement. The number of statements marked will be added up by the clinician and a total score is given. The total score ranges from 0 (no disability) to 24 (severe disability). | Baseline, Week 13, Week 54 | 
| Change From Baseline to Week 13 Endpoint in Weekly Mean of 24-hour Average Pain, Night Pain and Worst Pain by 11-Point Likert Scale | 24-hour average pain severity scores recorded daily on an 11-point Likert scale, an ordinal scale ranging from 0 (no pain) to 10 (worst possible pain). Patients should complete the electronic diary at bedtime. The 11-point Likert scale will also be used for assessment of night pain and worst pain each day, and evaluated as weekly means. Average interference was calculated as the average of non-missing scores of individual interference items. | Baseline, Week 13 | 
| Change From Baseline to Week 13 and Week 54 Endpoints in Brief Pain Inventory - Severity (BPI-S) and Interference (BPI-I) Scores | BPI-S and BPI-I are self-reported scales measuring severity of pain and interference on function. Severity scores: 0 (no pain) to 10 (severe pain) on each question assessing worst pain, least pain, and average pain in past 24 hours, and pain right now. 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 non-missing scores of individual interference items. | Baseline, Week 13, Week 54 | 
| Change From Baseline to Week 13 and Week 54 Endpoints in Clinical Global Impression of Severity (CGI-Severity) | 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). | Baseline, Week 13, Week 54 | 
| Number of Participants Who Responded to Treatment at Week 13 Endpoint Based on 30% Score Reduction Criteria | Response to treatment was defined as at least a 30% reduction of weekly mean score in in Brief Pain Inventory (BPI) Average Pain severity ratings from baseline to endpoint. The number of participants who met this criteria are presented. | Week 13 | 
| Number of Participants Who Responded to Treatment at Week 13 Endpoint Based on 50% Score Reduction Criteria | Response to treatment was defined as at least a 50% reduction of weekly mean score in in Brief Pain Inventory (BPI) Average Pain severity ratings from baseline to endpoint. The number of participants who met this criteria are presented. | Week 13 | 
| Change From Baseline to Week 13 and Week 54 Endpoints in Athens Insomnia Scale | Estimates sleep difficulty. Consists of 8 items rated on a 4-point scale of 0 (no problem at all) to 3 (very serious problem). Total score of the 8-item version ranges from 0-24. | Baseline, Week 13, Week 54 | 
| Change From Baseline to Week 13 Endpoint in 36-Item Short-Form Health Survey (SF-36) | The SF-36 Health Status Survey is a generic, health-related scale assessing subjects' quality of life on 8 domains: physical functioning, social functioning, bodily pain, vitality, mental health, role-physical, role-emotional and general health and 2 summary scores (mental component summary [MCS] and physical component summary [PCS]). MCS and PCS scores=0-100 (higher scores indicate better health status). Domain scores: general health=5-25; physical functioning=10-30; role-physical=4-8; role-emotional=3-6; social functioning=2-10; bodily pain=2-11; vitality=4-24; mental health=5-30. | Baseline, Week 13 | 
| Change From Baseline to Week 13 Endpoint in EuroQoL Questionnaire - 5 Dimension (EQ-5D) | The EuroQoL Questionnaire - 5 Dimension (EQ-5D) is a generic, multidimensional, health-related, quality-of-life instrument. The profile allows patients to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood. A single score between 1 and 3 is generated for each domain. For each patient, the outcome rating on the 5 domains will be mapped to a single index through an algorithm. The index ranges between 0 and 1, with the higher score indicating a better health state perceived by the patient. Scores presented used the UK Based Index Score. | Baseline, Week 13 | 
| Change From Baseline to Week 13 and Week 54 Endpoints in Work Productivity and Activity Impairment Instrument (WPAI) Scores | WPAI: self-administered instrument used to measure effect of general health and symptom severity on work productivity and regular activities and yields 4 types of scores: Absenteeism (work time missed); Presenteeism (impairment at work/reduced on-the-job effectiveness); Work Productivity Loss (overall work impairment/absenteeism plus presenteeism); and Activity Impairment. Higher scores are indicative of greater impairment. Absenteeism=(Q2/(Q2+Q4))*100 Presenteeism=(Q5/10)*100 Work productivity loss=(Q2/(Q2+Q4)+[(1-Q2/(Q2+Q4))x(Q5/10)])*100 Activity Impairment=(Q6/10)*100 | Baseline, Week 13, Week 54 | 
| Change From Baseline to Week 13 and Week 54 Endpoints in Beck Depression Inventory (BDI-II) Total Scores | A 21-item, patient-completed questionnaire to assess characteristics of depression. Each of the 21 items corresponding to a symptom of depression is summed to give a single score. There is a four-point scale for each item ranging from 0 to 3. Total score of 0-13 is considered minimal range, 14-19 is mild, 20-28 is moderate, and 29-63 is severe. | Baseline, Week 13, Week 54 | 
| Change From Baseline to Week 13 Endpoint in Hospital Anxiety and Depression Scale (HADS) Scores | A 14-item questionnaire with 2 subscales: anxiety and depression. Each item is rated on a 4-point scale, giving maximum scores of 21 for anxiety and depression. Scores of 11 or more on either subscale are considered to be a significant 'case' of psychological morbidity, while scores of 8-10 represent 'borderline' and 0-7, 'normal.' | Baseline, Week 13 | 
| Laboratory Assessments That Were Statistically Significantly Different Between Treatment Groups in Change From Baseline to Week 13 Endpoint: Bicarbonate |  | Baseline, Week 13 | 
| Laboratory Assessments That Were Statistically Significantly Different Between Treatment Groups in Change From Baseline to Week 13 Endpoint: Uric Acid |  | Baseline, Week 13 | 
| Change From Baseline to Week 13 and Week 54 Endpoints in Vital Signs: Pulse Rate |  | Baseline, Week 13, Week 54 | 
| Change From Baseline to Week 13 and Week 54 Endpoints in Vital Signs: Blood Pressure |  | Baseline, Week 13, Week 54 | 
| Change From Baseline to Week 13 and Week 54 Endpoints in Vital Signs: Weight |  | Baseline, Week 13, Week 54 |