A Study of Duloxetine in Adolescents With Juvenile Primary Fibromyalgia Syndrome

Study Overview
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Brief Summary
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The purpose of this study is to determine whether duloxetine is safe and effective in the treatment of adolescents with Juvenile Primary Fibromyalgia Syndrome (JPFS). This trial consists of two distinct study periods. A blinded treatment period of 13 weeks and an open label extension period of 26 weeks.

Official Title
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Effect of Duloxetine 30/60 mg Once Daily Versus Placebo in Adolescents With Juvenile Primary Fibromyalgia Syndrome

Conditions
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Fibromyalgia

Intervention / Treatment
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* Drug: Duloxetine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Meet criteria for primary JPFS Have a score of greater than or equal to 4 on Brief Pain Inventory (BPI) average pain severity (Item 3) during screening Female participants must have a negative serum pregnancy test during screening Participant's parent/legal representative and participant judged to be reliable to keep all appointments for clinical tests and procedures Participant's parent/legal representative and participant must have a degree of understanding such that they can communicate intelligently Participants must be capable of swallowing investigational product whole Participants must have venous access sufficient to allow blood sampling and be compliant with blood draws Exclusion Criteria: Currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational drug or device or off-label use of a drug or device or concurrently enrolled in any other type of medical research Previously completed or withdrawn after randomization from a study investigating duloxetine Known hypersensitivity to duloxetine or any of the inactive ingredients, or have frequent or severe allergic reactions to multiple medications Treated with duloxetine within the last 6 months. Will not likely benefit from duloxetine treatment, in the opinion of the investigator or have had prior nonresponse or inadequate tolerance to duloxetine Pain symptoms related to traumatic injury, past surgery, structural bone or joint disease or regional pain syndrome that will interfere with interpretation of outcome measures Currently have evidence of rheumatologic disorder or have a current diagnosis of rheumatoid arthritis, inflammatory arthritis, or infectious arthritis, or an autoimmune disease (for example, systemic lupus erythematosus) Have a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) Axis I condition, currently or within the past year, except major depressive disorder (MDD) and/or generalized anxiety disorder (GAD), adjustment disorder or specific phobias with primary investigator approval Have a current secondary DSM-IV Axis I condition of attention-deficit/hyperactivity disorder that requires pharmacologic treatment Lifetime DSM-IV Axis I diagnosis of psychosis, bipolar disorder, or schizoaffective disorder DSM-IV Axis II disorder which would interfere with protocol compliance History of substance abuse or dependence within the 6 months Positive urine drug screen for any substances of abuse or excluded medication Family history of 1 or more first-degree relatives with diagnosed bipolar I disorder Significant suicide attempt within 1 year of screening or are currently at suicidal risk in the opinion of the investigator Weight less than 20 kilogram (kg) at screening History of seizure disorder (other than febrile seizures) Taking any excluded medications that cannot be discontinued at screening Fluoxetine within 30 days prior to completion of screening Monoamine oxidase inhibitor (MAOI) within 14 days of screening; or the potential need to use an MAOI during the study or within 5 days of discontinuation of investigational product Abnormal thyroid-stimulating hormone (TSH) concentrations Uncontrolled narrow-angle glaucoma Acute liver injury (such as hepatitis) or severe cirrhosis (Child-Pugh Class C) Serious or unstable medical illness Female participants who are either pregnant, nursing or have recently given birth

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 17 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Duloxetine<br>Blinded treatment period: 30mg or 60mg once daily for 13 weeks Open label extension: 30mg or 60mg Duloxetine once daily for 26 weeks Taper period: 30mg Duloxetine or placebo once daily for 1 week. | Drug: Duloxetine<br>* Administered orally<br>* Other names: LY248686;|
| Placebo Comparator: Placebo<br>Blinded treatment period:Placebo once daily for 13 weeks Open label extension: 30mg or 60mg Duloxetine once daily for 26 weeks Taper period: 30mg Duloxetine or placebo once daily for 1 week. | Drug: Duloxetine<br>* Administered orally<br>* Other names: LY248686;Drug: Placebo<br>* Administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to 13 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-adolescent Version 24 Hour Average Pain Severity Item | Brief Pain Inventory (BPI) modified short form is a self-reported scale that measures the severity of pain and the interference of pain on function, Severity scores range from 0 (no pain) to 10 (pain as bad as you can imagine). Severity of pain is measured based on the average pain experienced over the past 24-hours. Mixed Model Repeated Measure (MMRM) model with terms for treatment, pooled investigator, visit, baseline, treatment by visit, and baseline by visit was used to produce Least Square (LS) means. | Baseline, 13 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to 13 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-Adolescent Version Severity and Interference Items | The Brief Pain Inventory (BPI) - Modified Short Form Adolescent Version is a self-reported scale that measures the severity of pain and the interference of pain on function. The Severity scores range from 0 (no pain) to 10 (pain as bad as you can imagine).There are 4 questions assessing the severity for worst pain, least pain, average pain in the past 24 hours (which is the primary efficacy measure), and the pain right now. The Interference scores range from 0 (does not interfere) to 10 (completely interferes). There are 7 original questions assessing the interference of pain in the past 24 hours on the following: general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. The BPI: Adolescent Version added an eighth interference question to assess interference of pain on school work. MMRM model with terms for treatment, pooled investigator, visit, baseline, treatment by visit, and baseline by visit was used to produce LS means. | Baseline, 13 weeks | 
| Maintenance Effect in Acute Phase Responders on the Brief Pain Inventory (BPI) Modified Short Form-adolescent Version 24 Hour Average Pain Severity Item | Brief Pain Inventory (BPI) modified short form is a self-reported scale that measures the severity of pain and the interference of pain on function.Severity scores range from 0 (no pain) to 10 (pain as bad as you can imagine). Severity of pain is measured based on the average pain experienced over the past 24-hours. Acute phase responders: Participants with ≥30% pain reduction from baseline on the BPI average pain severity measure at the last non-missing assessment in acute phase. | Baseline (Extension Phase), 39 weeks | 
| Number of Participants With Greater Than or Equal to 30% Reduction From Baseline in BPI 24 Hour Average Pain Severity Score at 13 Weeks | Brief Pain Inventory (BPI) modified short form is a self-reported scale that measures the severity of pain and interference of pain on function, Severity scores range from 0 (no pain) to 10 (pain as bad as you can imagine). Severity of pain is measured based on the average pain experienced over the past 24-hours. Percent reduction of BPI 24 hour average pain from baseline to last observation carried forward (LOCF). | 13 weeks | 
| Number of Participants With Greater Than or Equal to 50% Reduction From Baseline in BPI 24 Hour Average Pain Severity Score at 13 Weeks | Brief Pain Inventory (BPI) modified short form is a self-reported scale that measures the severity of pain and interference of pain on function, Severity scores range from 0 (no pain) to 10 (pain as bad as you can imagine). Severity of pain is measured based on the average pain experienced over the past 24-hours. Percent reduction of BPI 24 hour average pain from baseline to last observation carried forward (LOCF). | 13 weeks | 
| Change From Baseline in Pediatric Pain Questionnaire (PPQ) Item Scores | Pediatric Pain Questionnaire (PPQ) is a self-reported scale that measures the severity for pain now, worst pain, and average pain in the past week with 100 mm VAS (Visual Analog Scale). The severity scores range from 0 (no hurting, no discomfort, no pain) to 100 (hurting a whole lot, very uncomfortable, severe pain). Analysis of Covariance (ANCOVA) model with last observation carried forward (LOCF) was used to produce LS means with terms for treatment, pooled investigator and baseline value. | Baseline, 13 weeks | 
| Change From Baseline in Clinical Global Impression (CGI) Severity: Overall Illness Score | Clinical Global Impression of Severity: Overall Illness (CGI-S: Overall Illness) scale evaluates the severity of the overall illness of JPFS, including all relevant, associated symptoms. The scoring ranges from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). The scoring is based on observed and reported symptoms and behaviors over the past 7 days that are ongoing at the time of the Study Visit. Analysis of Covariance (ANCOVA) model with last observation carried forward (LOCF) was used to produce LS mean with terms for treatment, pooled investigator and baseline value. | Baseline, 13 weeks | 
| Change From Baseline in Clinical Global Impression (CGI) Severity: Mental Illness Score | Clinical Global Impression of Severity: Mental Illness (CGI-S: Mental Illness) scale evaluates the severity of any diagnosed, comorbid Axis I/II condition. The scoring ranges from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). Participants without a diagnosed Axis I/II condition should receive a score of 1 (normal, not at all ill). Analysis of Covariance (ANCOVA) model with last observation carried forward (LOCF) was used to produce LS mean with terms for treatment, pooled investigator and baseline value. | Baseline, 13 weeks | 
| Change From Baseline in Functional Disability Inventory Child Form (FDI-Child) | Functional Disability Inventory-child form (FDI-child) is a self-reported scale to assess the physical trouble or difficulty the child has doing regular activities. This scale contains 15 items. Each item is scored on a 0- to-4-point scale (0 = no trouble, 1 = a little trouble, 2 = some trouble, 3 = a lot of trouble, 4 = impossible).The total score ranges from 0 to 60. The higher the score, the more physical trouble or difficulty the child has doing regular activities. Analysis of Covariance (ANCOVA) model with last observation carried forward (LOCF) was used to produce LS means with terms for treatment, pooled investigator and baseline value. | Baseline, 13 weeks | 
| Change From Baseline in Functional Disability Inventory Parent Form (FDI-Parent) | Functional Disability Inventory-parent form (FDI-parent) contains the same items as FDI-child, but is reported by parent/legal representative. The total score range from 0 to 60. The higher the score, the more physical trouble or difficulty the child has doing regular activities. Analysis of Covariance (ANCOVA) model with last observation carried forward (LOCF) was used to produce LS means with terms for treatment, pooled investigator and baseline value. | Baseline, 13 weeks | 
| Change From Baseline in Children's Depression Inventory (CDI) | Children's Depression Inventory (CDI) is modeled after the Beck Depression Inventory and is a 27-item self-reported, symptom-oriented scale designed for school-aged children and adolescents. Each item is scored on a 0-to-2-point scale (in increasing severity) and thus the total score ranges from 0 to 54. The higher the score, the more severe the depression. Analysis of Covariance (ANCOVA) model with last observation carried forward (LOCF) was used to produce LS means with terms for treatment, pooled investigator and baseline value. | Baseline, 13 weeks | 
| Change From Baseline in Multidimensional Anxiety Scale for Children (MASC) | Multidimensional Anxiety Scale for Children (MASC) is a self-reported scale developed to assess anxiety in children and adolescents. The MASC consists of 39 items that comprise 4 factors with each item scored on a 0-to-3-point scale (0-never true about me, 1-rarely true about me, 2- sometimes true about me, 3-often true about me). : 1) physical symptoms (tense/restless and somatic/autonomic)-12 items with score range 0 to 36; 2) social anxiety (humiliation/rejection and public performance fears)-9 items with score range of 0 to 27; 3) harm avoidance (perfectionism and anxious coping)-9 items with score range of 0 to 27; and 4) separation anxiety-9 items with score range of 0 to 27. Total score ranges from 0 to 117. The higher the total score, the more severe the anxiety.Analysis of Covariance (ANCOVA) model with last observation carried forward (LOCF) was used to produce LS means with terms for treatment, pooled investigator and baseline value. | Baseline, 13 weeks | 
| Change From Baseline to 39 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-adolescent Version Severity and Interference Items | The BPI - Modified Short Form Adolescent Version is a self-reported scale that measures the severity of pain and the interference of pain on function. The Severity scores range from 0 (no pain) to 10 (pain as bad as you can imagine).There are 4 questions assessing the severity for worst pain, least pain, average pain in the past 24 hours (which is the primary efficacy measure), and the pain right now. The Interference scores range from 0 (does not interfere) to 10 (completely interferes). There are 7 original questions assessing the interference of pain in the past 24 hours on the following: general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. The BPI: Adolescent Version added an eighth interference question to assess interference of pain on school work. Analysis of Covariance (ANCOVA) model with last observation carried forward (LOCF) was used to produce LS means with terms for pooled investigator and baseline value. | Baseline (extension phase), 39 weeks | 
| Change From Baseline in Pediatric Pain Questionnaire (PPQ) Item Scores | Pediatric Pain Questionnaire (PPQ) is a self-reported scale that measures the severity for pain now, worst pain, and average pain in the past week with 100 mm VAS (Visual Analog Scale). The severity scores range from 0 (no hurting, no discomfort, no pain) to 100 (hurting a whole lot, very uncomfortable, severe pain). Analysis of Covariance (ANCOVA) model with last observation carried forward (LOCF) was used to produce LS means with terms for pooled investigator and baseline value. | Baseline (extension phase), 39 weeks | 
| Change From Baseline in Clinical Global Impression (CGI) Severity: Overall Illness Score | Clinical Global Impression of Severity: Overall Illness (CGI-S: Overall Illness) scale evaluates the severity of the overall illness of JPFS, including all relevant, associated symptoms. The scoring ranges from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). The scoring is based on observed and reported symptoms and behaviors over the past 7 days that are ongoing at the time of the Study Visit. Analysis of Covariance (ANCOVA) model with last observation carried forward (LOCF) was used to produce LS mean with terms for pooled investigator and baseline value. | Baseline (extension phase), 39 weeks | 
| Change From Baseline in Clinical Global Impression (CGI) Severity: Mental Illness Score | Clinical Global Impression of Severity: Mental Illness (CGI-S: Mental Illness) scale evaluates the severity of any diagnosed, comorbid Axis I/II condition. The scoring ranges from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). Participants without a diagnosed Axis I/II condition should receive a score of 1 (normal, not at all ill). Analysis of Covariance (ANCOVA) model with last observation carried forward (LOCF) was used to produce LS mean with terms for pooled investigator and baseline value. | Baseline (extension phase), 39 weeks | 
| Change From Baseline in Functional Disability Inventory Child Form (FDI-child) | Functional Disability Inventory-child form (FDI-child) is a self-reported scale to assess the physical trouble or difficulty the child has doing regular activities. This scale contains 15 items. Each item is scored on a 0- to-4-point scale (0 = no trouble, 1 = a little trouble, 2 = some trouble, 3 = a lot of trouble, 4 = impossible).The total score ranges from 0 to 60. The higher the score, the more physical trouble or difficulty the child has doing regular activities. Analysis of Covariance (ANCOVA) model with last observation carried forward (LOCF) was used to produce LS means with terms for pooled investigator and baseline value. | Baseline (extension phase), 39 weeks | 
| Change From Baseline in Functional Disability Inventory Parent Form (FDI-parent) | Functional Disability Inventory-parent form (FDI-parent) contains the same items as FDI-child, but is reported by parent/legal representative. The total score range from 0 to 60. The higher the score, the more physical trouble or difficulty the child has doing regular activities. Analysis of Covariance (ANCOVA) model with last observation carried forward (LOCF) was used to produce LS means with terms for pooled investigator and baseline value. | Baseline (extension phase), 39 weeks | 
| Change From Baseline in Children's Depression Inventory (CDI) | Children's Depression Inventory (CDI) is modeled after the Beck Depression Inventory and is a 27-item self-reported, symptom-oriented scale designed for school-aged children and adolescents. Each item is scored on a 0-to-2-point scale (in increasing severity) and thus the total score ranges from 0 to 54. The higher the score, the more severe the depression. Analysis of Covariance (ANCOVA) model with last observation carried forward (LOCF) was used to produce LS means with terms for pooled investigator and baseline value. | Baseline (extension phase), 39 weeks | 
| Change From Baseline in Multidimensional Anxiety Scale for Children (MASC) | Multidimensional Anxiety Scale for Children (MASC) is a self-reported scale developed to assess anxiety in children and adolescents. The MASC consists of 39 items that comprise 4 factors with each item scored on a 0-to-3-point scale (0-never true about me, 1-rarely true about me, 2- sometimes true about me, 3-often true about me). : 1) physical symptoms (tense/restless and somatic/autonomic)-12 items with score range 0 to 36; 2) social anxiety (humiliation/rejection and public performance fears)-9 items with score range of 0 to 27; 3) harm avoidance (perfectionism and anxious coping)-9 items with score range of 0 to 27; and 4) separation anxiety-9 items with score range of 0 to 27. Total score ranges from 0 to 117. The higher the total score, the more severe the anxiety.ANCOVA model with last observation carried forward (LOCF) was used to produce LS means with terms for pooled investigator and baseline value. | Baseline (extension phase), 39 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adolescents, Juvenile Primary Fibromyalgia Syndrome