An Open Label Extension Study of Duloxetine (LY248686) in Participants With Chronic Low Back Pain

Study Overview
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Brief Summary
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The purpose of the study is to assess the long term safety of duloxetine in participants with Chronic Low Back Pain (CLBP).

Official Title
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Phase 3 Clinical Study of Duloxetine Hydrochloride in Patients With CLBP - Open Label Long Term Extension Study

Conditions
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Back Pain Lower Back Chronic

Intervention / Treatment
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* Drug: Duloxetine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: (Consecutive Participants): Participants who have completed the 15-week administration in the phase 3 clinical study of Duloxetine hydrochloride in participants with CLBP, study HMGY (NCT01855919) Female participants having child-bearing potential must test negative (-) on a pregnancy test (New Participants): Participants with CLBP present for the preceding 6 months or longer Participants used nonsteroidal anti-inflammatory drugs for CLBP for less than 14 days on average per month in the past 3 months and less than 14 days in one month prior to study Participants having a score of ≥4 on Brief Pain Inventory (BPI) average pain score at participation of study Female participants having child-bearing potential must test negative (-) on a pregnancy test Exclusion Criteria: (Consecutive Participants): Participants having serious or unstable cardiovascular, hepatic, renal, metabolic, respiratory, or hematologic illness, symptomatic peripheral vascular disease, or other medical condition or psychiatric conditions that, in the opinion of investigator, would compromise participation or be likely to lead to hospitalization during the course of the study Participants having alanine aminotransferase or aspartate aminotransferase higher than 100 International Units per Liter (IU/L) or total bilirubin higher than 1.6 milligram per deciliter (mg/dL) Participants having serum creatinine level higher than 2.0 mg/dL, or had renal transplantation or receiving renal dialysis Participants having diagnosis seronegative spondyloarthropathy or rheumatoid arthritis Participants having primary painful condition due to other than CLBP Participants having uncorrected thyroid disease, uncontrolled narrow-angle glaucoma, history of uncontrolled seizures, or uncontrolled or poorly controlled hypertension Participants treating with a monoamine oxidase inhibitor (MAOI) within 14 days or the potential need to use an MAOI during the study or within 5 days of discontinuation of study drug Participants answering yes to any of the questions about active suicidal ideation/intent/behaviors occurring within the past month (Columbia Suicide Severity Rating Scale, Suicide Ideation section - Questions 4 and 5; Suicidal Behavior section) Pregnant participants or participants who are breast-feeding, or wished to be pregnant during the clinical trial period Participants cannot use appropriate contraceptive method or do not want to use that from participation of study until one month after the end of administration of the investigational drug Participants being considered as inappropriate for participation to the study for any medical or other reason as judged by the investigator (New Participants): Participants having serious or unstable cardiovascular, hepatic, renal, metabolic, respiratory, or hematologic illness, symptomatic peripheral vascular disease, or other medical condition or psychiatric conditions that, in the opinion of investigator, would compromise participation or be likely to lead to hospitalization during the course of the study Participants having alanine aminotransferase or aspartate aminotransferase higher than 100 IU/L or total bilirubin higher than 1.6 mg/dL Participants having serum creatinine level higher than 2.0 mg/dL, or had renal transplantation or receiving renal dialysis Participants having diagnosis seronegative spondyloarthropathy or rheumatoid arthritis Participants having primary painful condition due to other than CLBP Participants having a history of low back surgery Participants having any previous diagnosis of psychosis, bipolar disorder, or schizoaffective disorder Participants having major depressive disorder as determined using depression module of the Mini-International Neuropsychiatric Interview Participants having uncorrected thyroid disease, uncontrolled narrow-angle glaucoma, history of uncontrolled seizures, or uncontrolled or poorly controlled hypertension Participants treating with a MAOI within 14 days or the potential need to use an MAOI during the study or within 5 days of discontinuation of study drug Participants answering yes to any of the questions about active suicidal ideation/intent/behaviors occurring within the past month (Columbia Suicide Severity Rating Scale, Suicide Ideation section - Questions 4 and 5; Suicidal Behavior section) Participants have known hypersensitivity to multiple medications Participants are non-ambulatory or require the use of crutches or a walker Participants having a history of substance abuse or dependence within the past year, excluding nicotine and caffeine Participants having a positive urine drug screen for any substances of abuse Participants have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication Participants have had previous exposure to duloxetine or completed / withdrawn from any study investigating duloxetine Pregnant participants or participants who are breast-feeding, or wished to be pregnant during the clinical trial period Participants cannot use appropriate contraceptive method or do not want to use that from participation of study until one month after the end of administration of the investigational drug Participants being considered as inappropriate for participation to the study for any medical or other reason as judged by the investigator

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 79 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Duloxetine<br>Duloxetine 20 milligram (mg) for first week, 40 mg for second week and 60 mg for next 48 weeks administered orally once daily. Tapering week doses of 40 mg for first week and 20 mg for second week. | Drug: Duloxetine<br>* Administered orally<br>* Other names: LY248686;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Drug Related Adverse Events (AEs) or Any Serious AE's | A summary of serious AEs and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Event module. | Week 53 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Roland Morris Disability Questionnaire (RMDQ-24) to Week 50 | RMDQ-24 is a participant completed questionnaire and measures the degree of disability due to back pain. The questionnaire consists of 24 statements and the participant was instructed to put a mark next to each appropriate statement. The number of statements marked was summed by the clinician for a total score. The total score ranged from 0 (no disability) to 24 (severe disability). | Baseline, Week 50 | 
| Change From Baseline in 36-Item Short-Form Health Survey (SF-36) to Week 50 | SF-36 Health Status Survey is a generic, health-related scale assessing participant's quality of life on 8 domains: physical functioning, social functioning, bodily pain, vitality, mental health, role-physical, role-emotional and general health. Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale, with higher scores indicating better health status or functioning. | Baseline, Week 50 | 
| Change From Baseline in European Quality of Life Questionnaire-5 Dimension (EQ-5D) to Week 50 | The EQ-5D is a generic, multidimensional, health-related, quality-of-life instrument. The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood using a three level scale (no problem, some problems, and major problems). These combinations of attributes were converted into a weighted health-state Index Score according to the Japan population-based algorithm ranging from -0.111 to 1.0, with higher scores indicating better quality of life. | Baseline, Week 50 | 
| Change From Baseline in Beck Depression Inventory-II (BDI-II) to Week 50 | BDI-II is a 21-item, participant-completed questionnaire to assess characteristics of depression. Each of the 21 items corresponding to symptoms of depression were scored on a 4-point scale ranging from 0 to 3 and was summed to give a single score. A total score of 0-13 was considered minimal range, 14-19 was mild, 20-28 was moderate, and 29-63 was severe. | Baseline, Week 50 | 
| Change From Baseline in Columbia Suicide Severity Rating Scale (C-SSRS) to Week 52 | C-SSRS captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal behavior is defined as a yes answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation is defined as a yes answer to any one of 5 suicidal ideation questions: wish to be dead, and 4 different categories of active suicidal ideation. | Baseline, Week 53 | 
| Number of Participants With Fall Events From Fall Questionnaire | Participants evaluated their experience with and details of falls which were recorded. Percentage = (number of participants with fall events) /(total in treatment group) * 100. | Week 53 | 
| Change From Baseline in Brief Pain Inventory (BPI) Pain Severity Item and Interference Item to Week 50 | A self-reported scale 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 50 | 
| Patient Global Impression of Improvement (PGI-Improvement) to Week 50 | PGI-I measures a participant's perception of improvement at the time of assessment compared with the start of treatment. Score ranges from 1 (very much better) to 7 (very much worse). | Week 50 | 
| Change From Baseline in Clinical Global Impression of Severity (CGI-Severity) to Week 50 | CGI-S measures severity of illness at the time of assessment compared with start of treatment with scores ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). | Baseline, Week 50 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Low Back Pain, CLBP