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.

Official Title
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Protocol F1J-MC-HMEO Duloxetine Versus Placebo in the Treatment of 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. Exclusion Criteria: - You have a serious or unstable disease 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, or 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 major depressive disorder. - Require daily narcotics.

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 20 mg<br>duloxetine 20 mg once a day (QD), by mouth (PO) for 13 weeks | Drug: Duloxetine<br> <br> * Other names: Cymbalta;|
| Experimental: Duloxetine 60 mg<br>duloxetine 30 mg once a day (QD), by mouth (PO) for 1 week then duloxetine 60 mg QD, PO for 12 weeks | Drug: Duloxetine<br> <br> * Other names: Cymbalta;|
| Experimental: Duloxetine 120 mg<br>duloxetine 30 mg once a day (QD), by mouth (PO) for 1 week followed by duloxetine 60 mg QD, PO for 1 week, then duloxetine 120 mg QD, PO for 11 weeks | Drug: Duloxetine<br> <br> * Other names: Cymbalta;|
| Placebo Comparator: Placebo<br>placebo once a day (QD), by mouth (PO) for 13 weeks | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 1 in Weekly Mean of the 24-hour Average Pain Scores | 24-hour average pain severity scores recorded daily on an 11-point Likert scale, evaluated as a weekly mean (Week 1), with scores ranging from 0 (no pain) to 10 (worst possible pain). | Baseline, Week 1 | 
| Change From Baseline to Week 2 in Weekly Mean of the 24-Hour Average Pain Scores | 24-hour average pain severity scores recorded daily on an 11-point Likert scale, evaluated as a weekly mean (Week 2), with scores ranging from 0 (no pain) to 10 (worst possible pain). | Baseline, Week 2 | 
| Change From Baseline to Week 3 in Weekly Mean of the 24-Hour Average Pain Scores | 24-hour average pain severity scores recorded daily on an 11-point Likert scale, evaluated as a weekly mean (Week 3), with scores ranging from 0 (no pain) to 10 (worst possible pain). | Baseline, Week 3 | 
| Change From Baseline to Week 4 in Weekly Mean of the 24-Hour Average Pain Scores | 24-hour average pain severity scores recorded daily on an 11-point Likert scale, evaluated as a weekly mean (Week 4), with scores ranging from 0 (no pain) to 10 (worst possible pain). | Baseline, Week 4 | 
| Change From Baseline to Week 5 in Weekly Mean of the 24-Hour Average Pain Scores | 24-hour average pain severity scores recorded daily on an 11-point Likert scale, evaluated as a weekly mean (Week 5), with scores ranging from 0 (no pain) to 10 (worst possible pain). | Baseline, Week 5 | 
| Change From Baseline to Week 6 in Weekly Mean of the 24-Hour Average Pain Scores | 24-hour average pain severity scores recorded daily on an 11-point Likert scale, evaluated as a weekly mean (Week 6), with scores ranging from 0 (no pain) to 10 (worst possible pain). | Baseline, Week 6 | 
| Change From Baseline to Week 7 in Weekly Mean of the 24-Hour Average Pain Scores | 24-hour average pain severity scores recorded daily on an 11-point Likert scale, evaluated as a weekly mean (Week 7), with scores ranging from 0 (no pain) to 10 (worst possible pain). | Baseline, Week 7 | 
| Change From Baseline to Week 8 in Weekly Mean of the 24-Hour Average Pain Scores | 24-hour average pain severity scores recorded daily on an 11-point Likert scale, evaluated as a weekly mean (Week 8), with scores ranging from 0 (no pain) to 10 (worst possible pain). | Baseline, Week 8 | 
| Change From Baseline to Week 9 in Weekly Mean of the 24-Hour Average Pain Scores | 24-hour average pain severity scores recorded daily on an 11-point Likert scale, evaluated as a weekly mean (Week 1), with scores ranging from 0 (no pain) to 10 (worst possible pain). | Baseline, Week 9 | 
| Change From Baseline to Week 10 in Weekly Mean of the 24-Hour Average Pain Scores | 24-hour average pain severity scores recorded daily on an 11-point Likert scale, evaluated as a weekly mean (Week 10), with scores ranging from 0 (no pain) to 10 (worst possible pain). | Baseline, Week 10 | 
| Change From Baseline to Week 11 in Weekly Mean of the 24-Hour Average Pain Scores | 24-hour average pain severity scores recorded daily on an 11-point Likert scale, evaluated as a weekly mean (Week 11), with scores ranging from 0 (no pain) to 10 (worst possible pain). | Baseline, Week 11 | 
| Change From Baseline to Week 12 in Weekly Mean of the 24-Hour Average Pain Scores | 24-hour average pain severity scores recorded daily on an 11-point Likert scale, evaluated as a weekly mean (Week 12), with scores ranging from 0 (no pain) to 10 (worst possible pain). | Baseline, Week 12 | 
| Change From Baseline to Week 13 Endpoint in Weekly Mean of the 24-Hour Average Pain Scores | 24-hour average pain severity scores recorded daily on an 11-point Likert scale, evaluated as a weekly mean (Week 13), with scores ranging from 0 (no pain) to 10 (worst possible pain). | Baseline, Week 13 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient's Global Impression - Improvement (PGI-I) at Week 13 Endpoint | 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 13 | 
| Change From Baseline to Week 13 Endpoint in Roland-Morris Disability Questionnaire (RMDQ) Total Score | Roland-Morris questionnaire was completed by the patient and measured the degree of disability due to back pain. The questionnaire consists of 24 statements and the patient was instructed to put a mark next to each appropriate statement. The number of statements marked was added up by the clinician and a total score was given. The total score ranges from 0 (no disability) to 24 (severe disability). | Baseline, Week 13 | 
| Change From Baseline to Week 13 Endpoint in the 11-point Likert Scale, Weekly Mean 24-Hour Night Pain Score | The 11-point Likert scale was used for assessment of 24-hour night pain and evaluated as weekly means. Scores range from from 0 (no pain) to 10 (worst possible pain). | Baseline, Week 13 | 
| Change From Baseline to Week 13 Endpoint in the 11-point Likert Scale, Weekly Mean of Worst Pain Score | The 11-point Likert scale was used for assessment of 24-hour worst pain and evaluated as weekly means. Scores range from from 0 (no pain) to 10 (worst possible pain). | Baseline, Week 13 | 
| Change From Baseline to Week 13 Endpoint in Clinical Global Impression of Severity | Measures severity of illness at the time of assessment compared with start of treatment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). | Baseline, Week 13 | 
| Change From Baseline to Week 13 Endpoint in Brief Pain Inventory Severity (BPI-S) - Worst Pain Score | A self-reported scale that measures the severity of pain based on the worst pain experienced 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 | 
| Change From Baseline to Week 13 Endpoint in Brief Pain Inventory Severity (BPI-S) - Least Pain Score | A self-reported scale that measures the severity of pain based on the least pain experienced 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 | 
| Change From Baseline to Week 13 Endpoint in Brief Pain Inventory Severity (BPI-S) - Average Pain Score |  | Baseline, Week 13 | 
| Change From Baseline to Week 13 Endpoint in Brief Pain Inventory Severity (BPI-S) - Pain Right Now Score | A self-reported scale that measures the severity of pain based on the pain right now. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). | Baseline, Week 13 | 
| Change From Baseline to Week 13 Endpoint in Brief Pain Inventory Interference (BPI-I) Score - General Activity | A self-reported scale that measures the interference of pain in the past 24 hours on general acitivity. The Interference scores range from 0 (does not interfere) to 10 (completely interferes). | Baseline, Week 13 | 
| Change From Baseline to Week 13 Endpoint in Brief Pain Inventory Interference (BPI-I) Score - Mood | A self-reported scale that measures the interference of pain in the past 24 hours on mood. The Interference scores range from 0 (does not interfere) to 10 (completely interferes). | Baseline, Week 13 | 
| Change From Baseline to Week 13 Endpoint in Brief Pain Inventory Interference (BPI-I) Score - Walking Ability | A self-reported scale that measures the interference of pain in the past 24 hours on walking ability. The Interference scores range from 0 (does not interfere) to 10 (completely interferes). | Baseline, Week 13 | 
| Change From Baseline to Week 13 Endpoint in Brief Pain Inventory Interference (BPI-I) Score - Normal Work | A self-reported scale that measures the interference of pain in the past 24 hours on normal work. The Interference scores range from 0 (does not interfere) to 10 (completely interferes). | Baseline, Week 13 | 
| Change From Baseline to Week 13 Endpoint in Brief Pain Inventory Interference (BPI-I) Score - Relations With Other People | A self-reported scale that measures the interference of pain in the past 24 hours on relations with other people. The Interference scores range from 0 (does not interfere) to 10 (completely interferes). | Baseline, Week 13 | 
| Change From Baseline to Week 13 Endpoint in Brief Pain Inventory Interference (BPI-I) Score - Sleep | A self-reported scale that measures the interference of pain in the past 24 hours on sleep. The Interference scores range from 0 (does not interfere) to 10 (completely interferes). | Baseline, Week 13 | 
| Change From Baseline to Week 13 Endpoint in Brief Pain Inventory Interference (BPI-I) Score - Enjoyment of Life | A self-reported scale that measures the interference of pain in the past 24 hours on enjoyment of life. The Interference scores range from 0 (does not interfere) to 10 (completely interferes). | Baseline, Week 13 | 
| Change From Baseline to Week 13 Endpoint in Brief Pain Inventory Interference (BPI-I) Score - Average Interference | A self-reported scale that measures interference of pain on average of the 7 questions assessing the interference of pain for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. The average Interference scores range from 0 (does not interfere) to 10 (completely interferes). | Baseline, Week 13 | 
| Response to Treatment, as Defined by a 30% Reduction of Weekly Mean Score in 24-hour Average Pain Severity Ratings, Last Observation Carried Forward |  | Baseline to Week 13 | 
| Response to Treatment, as Defined by a 50% Reduction of Weekly Mean Score in 24-hour Average Pain Severity Ratings, Last Observation Carried Forward |  | Baseline to Week 13 | 
| Change From Baseline to Week 13 Endpoint 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 | 
| Change From Baseline to Week 13 Endpoint in the 36-item Short-Form Health Survey (SF36)- Mental Component Summary (MCS) | 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). | Baseline, Week 13 | 
| Change From Baseline to Week 13 Endpoint in 36-Item Short-Form Health Survey (SF36) - Physical Component Summary (PCS) | 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). | Baseline, Week 13 | 
| Change From Baseline to Week 13 Endpoint in 36-Item Short-Form Health Survey (SF36) - Bodily Pain | 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]). Bodily pain scores range from 2-11 (higher scores indicate better health status). | Baseline, Week 13 | 
| Change From Baseline to Week 13 Endpoint in 36-Item Short-Form Health Survey (SF36) - General Health | 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]). General health scores range from 5-25(higher scores indicate better health status). | Baseline, Week 13 | 
| Change From Baseline to Week 13 Endpoint in 36-Item Short-Form Health Survey (SF36) - Mental Health | 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]). Mental health scores range from 5-30 (higher scores indicate better health status). | Baseline, Week 13 | 
| Change From Baseline to Week 13 Endpoint in 36-Item Short-Form Health Survey (SF36) - Physical Functioning | 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]). Physical functioning scores range from 10-30 (higher scores indicate better health status). | Baseline, Week 13 | 
| Change From Baseline to Week 13 Endpoint in 36-Item Short-Form Health Survey (SF36) - Role-Emotional | 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]). Role-emotional scores range from 3-6 (higher scores indicate better health status). | Baseline, Week 13 | 
| Change From Baseline to Week 13 Endpoint in 36-Item Short-Form Health Survey (SF36) - Role-Physical | 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]). Role-physical scores range from 4-8 (higher scores indicate better health status). | Baseline, Week 13 | 
| Change From Baseline to Week 13 Endpoint in 36-Item Short-Form Health Survey (SF36) - Social Functioning | 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]). Social functioning scores range from 2-10 (higher scores indicate better health status). | Baseline, Week 13 | 
| Change From Baseline to Week 13 Endpoint in 36-Item Short-Form Health Survey (SF36) - Vitality | 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]). Vitality scores range from 4-24 (higher scores indicate better health status). | Baseline, Week 13 | 
| Change From Baseline to Week 13 Endpoint in the Euro-Quality of Life Questionnaire - 5 Dimension - US Based Index Score | 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. | Baseline, Week 13 | 
| Change From Baseline to Week 13 Endpoint in Beck Depression Inventory-II Total Score | 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 | 
| Change From Baseline to Week 13 Endpoint in Hospital Anxiety and Depression Scale (HADS) Anxiety Subscale | 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 | 
| Adverse Events Reported as Reason for Discontinuation |  | Baseline to Week 13 | 
| Change From Baseline to Week 13 Endpoint in Laboratory Assessments - Alkaline Phosphatase |  | Baseline, Week 13 | 
| Change From Baseline to 13 Week Endpoint in Laboratory Assessments - Alanine Transaminase |  | Baseline, Week 13 | 
| Change From Baseline to Week 13 Endpoint in Laboratory Assessment - Bicarbonate, HCO3 |  | Baseline, Week 13 | 
| Change From Baseline to Week 13 Endpoint in Laboratory Assessment - Bilirubin, Direct |  | Baseline, Week 13 | 
| Change From Baseline to Week 13 Endpoint in Laboratory Assessment - Bilirubin, Total |  | Baseline, Week 13 | 
| Change From Baseline to Week 13 Endpoint in Laboratory Assessment - Chloride |  | Baseline, Week 13 | 
| Change From Baseline to Week 13 Endpoint in Laboratory Assessment - Cholesterol |  | Baseline, Week 13 | 
| Change From Baseline to Week 13 Endpoint in Laboratory Assessment - Creatinine |  | Baseline, Week 13 | 
| Change From Baseline to Week 13 Endpoint in Laboratory Assessment - Potassium |  | Baseline, Week 13 | 
| Change From Baseline to Week 13 Endpoint in Laboratory Assessment - Uric Acid |  | Baseline, Week 13 | 
| Change From Baseline to Week 13 Endpoint in Vital Signs - Pulse Rate |  | Baseline, Week 13 | 
| Change From Baseline to Week 13 Endpoint in Vital Signs - Systolic Blood Pressure |  | Baseline, Week 13 | 
| Change From Baseline to Week 13 Endpoint in Vital Signs - Diastolic Blood Pressure |  | Baseline, Week 13 | 
| Change From Baseline to Week 13 Endpoint in Vital Signs - Weight |  | Baseline, Week 13 |