Fibromyalgia
Conditions
Keywords
Adolescents, Juvenile Primary Fibromyalgia Syndrome
Brief summary
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.
Interventions
DRUGDuloxetine
Administered orally
DRUGPlacebo
Administered orally
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
13 Years to 17 Years
Healthy volunteers
No
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use of a drug or device or concurrently enrolled in any other type of medical research * Previously completed or withdrawn after randomization from a study investigating duloxetine * Known hypersensitivity to duloxetine or any of the inactive ingredients, or have frequent or severe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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to 13 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-adolescent Version 24 Hour Average Pain Severity Item | Baseline, 13 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maintenance Effect in Acute Phase Responders on the Brief Pain Inventory (BPI) Modified Short Form-adolescent Version 24 Hour Average Pain Severity Item | Baseline (Extension Phase), 39 weeks | 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. |
| Number of Participants With Greater Than or Equal to 30% Reduction From Baseline in BPI 24 Hour Average Pain Severity Score at 13 Weeks | 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). |
| Number of Participants With Greater Than or Equal to 50% Reduction From Baseline in BPI 24 Hour Average Pain Severity Score at 13 Weeks | 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). |
| Change From Baseline in Pediatric Pain Questionnaire (PPQ) Item Scores | Baseline, 13 weeks | 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. |
| Change From Baseline in Clinical Global Impression (CGI) Severity: Overall Illness Score | Baseline, 13 weeks | 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. |
| Change From Baseline in Clinical Global Impression (CGI) Severity: Mental Illness Score | Baseline, 13 weeks | 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. |
| Change From Baseline to 13 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-Adolescent Version Severity and Interference Items | Baseline, 13 weeks | 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. |
| Change From Baseline in Functional Disability Inventory Parent Form (FDI-Parent) | Baseline, 13 weeks | 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. |
| Change From Baseline in Children's Depression Inventory (CDI) | Baseline, 13 weeks | 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. |
| Change From Baseline in Multidimensional Anxiety Scale for Children (MASC) | Baseline, 13 weeks | 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. |
| Change From Baseline to 39 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-adolescent Version Severity and Interference Items | Baseline (extension phase), 39 weeks | 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. |
| Change From Baseline in Functional Disability Inventory Child Form (FDI-child) | Baseline (extension phase), 39 weeks | 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. |
| Change From Baseline in Functional Disability Inventory Parent Form (FDI-parent) | Baseline (extension phase), 39 weeks | 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. |
| Change From Baseline in Functional Disability Inventory Child Form (FDI-Child) | Baseline, 13 weeks | 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. |
Countries
Argentina, India, Puerto Rico, United States
Participant flow
Recruitment details
13 week Double-Blind Treatment Phase (Acute Phase), followed by 26 week Open-Label Extension Treatment Phase (Extension Phase), followed by 1 week Taper/Discontinuation Phase.
Participants by arm
| Arm | Count |
|---|---|
| Duloxetine Participants received flexible doses of 30 or 60 milligram (mg) Duloxetine orally once daily (QD) for 13 weeks during double blind treatment period (Acute Phase) and flexible doses of 30 or 60 milligram (mg) Duloxetine orally once daily (QD) for 26 weeks during open label extension treatment period (Extension Phase).
Participants who received higher doses of Duloxetine in acute & extension phase received gradually lower doses of duloxetine & participants on lower doses of Duloxetine in acute phase received placebo during 1-week tapering phase. | 91 |
| Placebo Participants received Placebo orally once daily (QD) for 13 weeks during double blind treatment phase and flexible doses of 30 or 60 milligram (mg) Duloxetine orally once daily (QD) for 26 weeks during open label extension treatment period (Extension Phase).
Participants who received placebo in acute phase received placebo & participants who received higher doses of Duloxetine in extension phase received gradually lower doses of duloxetine during 1-week tapering phase. | 93 |
| Total | 184 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double Blind Treatment (Acute Phase) | Adverse Event | 5 | 1 |
| Double Blind Treatment (Acute Phase) | Lack of Efficacy | 1 | 3 |
| Double Blind Treatment (Acute Phase) | Lost to Follow-up | 2 | 3 |
| Double Blind Treatment (Acute Phase) | Parent/Caregiver Decision | 2 | 4 |
| Double Blind Treatment (Acute Phase) | Protocol Violation | 4 | 3 |
| Double Blind Treatment (Acute Phase) | Withdrawal by Subject | 3 | 4 |
| Open Label Treatment (Extension Phase) | Adverse Event | 5 | 5 |
| Open Label Treatment (Extension Phase) | Lack of Efficacy | 2 | 4 |
| Open Label Treatment (Extension Phase) | Lost to Follow-up | 4 | 3 |
| Open Label Treatment (Extension Phase) | Parent/Guardian Decision | 2 | 4 |
| Open Label Treatment (Extension Phase) | Physician Decision | 4 | 4 |
| Open Label Treatment (Extension Phase) | Sponsor Decision | 1 | 0 |
| Open Label Treatment (Extension Phase) | Withdrawal by Subject | 0 | 5 |
| Taper Phase | Adverse Event | 0 | 2 |
| Taper Phase | Lack of Efficacy | 2 | 5 |
| Taper Phase | Parent/Guardian Decision | 0 | 2 |
| Taper Phase | Protocol Violation | 2 | 0 |
| Taper Phase | Sponsor Decision | 1 | 0 |
| Taper Phase | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | Duloxetine | Total |
|---|---|---|---|
| Age, Continuous | 15.33 years STANDARD_DEVIATION 1.421 | 15.74 years STANDARD_DEVIATION 1.379 | 15.53 years STANDARD_DEVIATION 1.411 |
| Brief Pain Inventory (BPI) Modified short form (SF) Adolescent version (AV) Average Pain | 5.6 units on a scale STANDARD_DEVIATION 1.55 | 5.7 units on a scale STANDARD_DEVIATION 1.37 | 5.65 units on a scale STANDARD_DEVIATION 1.46 |
| Brief Pain Inventory (BPI) Modified short form (SF) Adolescent version (AV) Enjoyment of Life | 4.3 units on a scale STANDARD_DEVIATION 2.8 | 4.1 units on a scale STANDARD_DEVIATION 3.1 | 4.2 units on a scale STANDARD_DEVIATION 3 |
| Brief Pain Inventory (BPI) Modified short form (SF) Adolescent version (AV) General Activity | 5.1 units on a scale STANDARD_DEVIATION 2 | 5.2 units on a scale STANDARD_DEVIATION 2 | 5.2 units on a scale STANDARD_DEVIATION 2.3 |
| Brief Pain Inventory (BPI) Modified short form (SF) Adolescent version (AV) Least Pain | 3.8 units on a scale STANDARD_DEVIATION 2 | 3.7 units on a scale STANDARD_DEVIATION 2.1 | 3.8 units on a scale STANDARD_DEVIATION 2.1 |
| Brief Pain Inventory (BPI) Modified short form (SF) Adolescent version (AV) Mood | 5.0 units on a scale STANDARD_DEVIATION 2.6 | 4.9 units on a scale STANDARD_DEVIATION 2.6 | 5.0 units on a scale STANDARD_DEVIATION 2.6 |
| Brief Pain Inventory (BPI) Modified short form (SF) Adolescent version (AV) Normal Work | 4.9 units on a scale STANDARD_DEVIATION 2.5 | 4.6 units on a scale STANDARD_DEVIATION 2.6 | 4.8 units on a scale STANDARD_DEVIATION 2.6 |
| Brief Pain Inventory (BPI) Modified short form (SF) Adolescent version (AV) Pain Right Now | 5.2 units on a scale STANDARD_DEVIATION 2.3 | 5.2 units on a scale STANDARD_DEVIATION 2.4 | 5.2 units on a scale STANDARD_DEVIATION 2.4 |
| Brief Pain Inventory (BPI) Modified short form (SF) Adolescent version (AV) Relations with other people | 3.7 units on a scale STANDARD_DEVIATION 2.8 | 3.7 units on a scale STANDARD_DEVIATION 2.7 | 3.7 units on a scale STANDARD_DEVIATION 2.8 |
| Brief Pain Inventory (BPI) Modified short form (SF) Adolescent version (AV) School Work | 4.3 units on a scale STANDARD_DEVIATION 3.2 | 4.8 units on a scale STANDARD_DEVIATION 3 | 4.6 units on a scale STANDARD_DEVIATION 3.1 |
| Brief Pain Inventory (BPI) Modified short form (SF) Adolescent version (AV) Sleep | 5.5 units on a scale STANDARD_DEVIATION 3 | 5.9 units on a scale STANDARD_DEVIATION 2.8 | 5.7 units on a scale STANDARD_DEVIATION 2.9 |
| Brief Pain Inventory (BPI) Modified short form (SF) Adolescent version (AV) Walking Ability | 4.5 units on a scale STANDARD_DEVIATION 2.8 | 4.1 units on a scale STANDARD_DEVIATION 2.8 | 4.3 units on a scale STANDARD_DEVIATION 2.8 |
| Brief Pain Inventory (BPI) Modified short form (SF) Adolescent version (AV) Worst Pain | 6.9 units on a scale STANDARD_DEVIATION 1.9 | 7.1 units on a scale STANDARD_DEVIATION 1.8 | 7.0 units on a scale STANDARD_DEVIATION 1.9 |
| Children's Depression Inventory (CDI) | 13.1 units on a scale STANDARD_DEVIATION 7.7 | 13.5 units on a scale STANDARD_DEVIATION 7.1 | 13.3 units on a scale STANDARD_DEVIATION 7.4 |
| Clinical Global Impression (CGI) Severity: Mental Illness | 2.0 units on a scale STANDARD_DEVIATION 1.1 | 2.1 units on a scale STANDARD_DEVIATION 1.2 | 2.05 units on a scale STANDARD_DEVIATION 1.15 |
| Clinical Global Impression (CGI) Severity: Overall Illness | 4.1 units on a scale STANDARD_DEVIATION 0.8 | 4.1 units on a scale STANDARD_DEVIATION 0.9 | 4.1 units on a scale STANDARD_DEVIATION 0.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 39 Participants | 36 Participants | 75 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 54 Participants | 54 Participants | 108 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Functional Disability Inventory (FDI) Child score | 22.3 units on a scale STANDARD_DEVIATION 9.9 | 23.3 units on a scale STANDARD_DEVIATION 11.1 | 22.8 units on a scale STANDARD_DEVIATION 10.5 |
| Functional Disability Inventory (FDI) Parent Score | 22.3 units on a scale STANDARD_DEVIATION 10.7 | 22.4 units on a scale STANDARD_DEVIATION 11.4 | 22.4 units on a scale STANDARD_DEVIATION 11.1 |
| Multidimensional Anxiety Scale for Children (MASC) Harm Avoidance | 14.4 units on a scale STANDARD_DEVIATION 4.7 | 15.0 units on a scale STANDARD_DEVIATION 4.2 | 14.7 units on a scale STANDARD_DEVIATION 4.5 |
| Multidimensional Anxiety Scale for Children (MASC) Physical Symptoms | 13.6 units on a scale STANDARD_DEVIATION 7.6 | 13.6 units on a scale STANDARD_DEVIATION 7.3 | 13.6 units on a scale STANDARD_DEVIATION 7.5 |
| Multidimensional Anxiety Scale for Children (MASC) Separation/Panic | 6.0 units on a scale STANDARD_DEVIATION 4.5 | 6.7 units on a scale STANDARD_DEVIATION 4.9 | 6.4 units on a scale STANDARD_DEVIATION 4.7 |
| Multidimensional Anxiety Scale for Children (MASC) Social Anxiety | 9.8 units on a scale STANDARD_DEVIATION 6.3 | 9.8 units on a scale STANDARD_DEVIATION 6.3 | 9.8 units on a scale STANDARD_DEVIATION 6.6 |
| Multidimensional Anxiety Scale for Children (MASC) Total Score | 43.9 units on a scale STANDARD_DEVIATION 18.7 | 45.1 units on a scale STANDARD_DEVIATION 16.6 | 44.5 units on a scale STANDARD_DEVIATION 17.65 |
| Pediatric Pain Questionnaire (PPQ) Average Pain | 58.1 mm STANDARD_DEVIATION 22.3 | 61.8 mm STANDARD_DEVIATION 19.5 | 58.94 mm STANDARD_DEVIATION 20.9 |
| Pediatric Pain Questionnaire (PPQ) pain now | 52.0 mm STANDARD_DEVIATION 25.2 | 50.1 mm STANDARD_DEVIATION 27.5 | 51.0 mm STANDARD_DEVIATION 26.4 |
| Pediatric Pain Questionnaire (PPQ) Worst Pain | 75.5 mm STANDARD_DEVIATION 20.4 | 77.4 mm STANDARD_DEVIATION 20.3 | 76.5 mm STANDARD_DEVIATION 20.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 7 Participants | 6 Participants | 13 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 7 Participants | 15 Participants |
| Race (NIH/OMB) More than one race | 6 Participants | 4 Participants | 10 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 70 Participants | 72 Participants | 142 Participants |
| Region of Enrollment Argentina | 19 Participants | 19 Participants | 38 Participants |
| Region of Enrollment India | 7 Participants | 6 Participants | 13 Participants |
| Region of Enrollment Puerto Rico | 3 Participants | 2 Participants | 5 Participants |
| Region of Enrollment United States | 64 Participants | 64 Participants | 128 Participants |
| Sex: Female, Male Female | 65 Participants | 73 Participants | 138 Participants |
| Sex: Female, Male Male | 28 Participants | 18 Participants | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 91 | 0 / 93 | 0 / 74 | 0 / 75 | 0 / 77 | 0 / 3 |
| other Total, other adverse events | 74 / 91 | 58 / 93 | 52 / 74 | 54 / 75 | 7 / 77 | 0 / 3 |
| serious Total, serious adverse events | 2 / 91 | 0 / 93 | 3 / 74 | 3 / 75 | 0 / 77 | 0 / 3 |
Outcome results
Primary
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.
Time frame: Baseline, 13 weeks
Population: All randomized participants who received at least one dose of study drug and had baseline \& at least one post baseline BPI average pain score.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine - Acute | Change From Baseline to 13 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-adolescent Version 24 Hour Average Pain Severity Item | -1.62 units on a scale | Standard Error 0.247 |
| Placebo - Acute | Change From Baseline to 13 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-adolescent Version 24 Hour Average Pain Severity Item | -0.97 units on a scale | Standard Error 0.244 |
p-value: 0.05295% CI: [-1.3, 0]Repeated Measures
Secondary
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.
Time frame: Baseline, 13 weeks
Population: All randomized participants who received at least one dose of study drug and had baseline \& at least one post baseline CDI score.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine - Acute | Change From Baseline in Children's Depression Inventory (CDI) | -3.28 units on a scale | Standard Error 0.682 |
| Placebo - Acute | Change From Baseline in Children's Depression Inventory (CDI) | -2.45 units on a scale | Standard Error 0.674 |
p-value: 0.33595% CI: [-2.52, 0.86]ANCOVA
Secondary
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.
Time frame: Baseline (extension phase), 39 weeks
Population: All randomized participants who received at least one dose of study drug \& had baseline \& at least one post baseline CDI measurement.~Baseline for extension phase is defined as the last non-missing value in acute phase.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine - Acute | Change From Baseline in Children's Depression Inventory (CDI) | -0.42 units on a scale | Standard Error 0.703 |
| Placebo - Acute | Change From Baseline in Children's Depression Inventory (CDI) | -1.41 units on a scale | Standard Error 0.681 |
Secondary
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.
Time frame: Baseline (extension phase), 39 weeks
Population: All randomized participants who received at least one dose of study drug \& had baseline \& at least one post baseline CGI mental Illness measurement.~Baseline for extension phase is defined as the last non-missing value in acute phase.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine - Acute | Change From Baseline in Clinical Global Impression (CGI) Severity: Mental Illness Score | -0.20 units on a scale | Standard Error 0.104 |
| Placebo - Acute | Change From Baseline in Clinical Global Impression (CGI) Severity: Mental Illness Score | -0.24 units on a scale | Standard Error 0.101 |
Secondary
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.
Time frame: Baseline, 13 weeks
Population: All randomized participants who received at least one dose of study drug and had baseline \& at least one post baseline CGI-S mental illness score.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine - Acute | Change From Baseline in Clinical Global Impression (CGI) Severity: Mental Illness Score | -0.16 units on a scale | Standard Error 0.089 |
| Placebo - Acute | Change From Baseline in Clinical Global Impression (CGI) Severity: Mental Illness Score | -0.15 units on a scale | Standard Error 0.087 |
p-value: 0.92795% CI: [-0.23, 0.21]ANCOVA
Secondary
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.
Time frame: Baseline (extension phase), 39 weeks
Population: All randomized participants who received at least one dose of study drug \& had baseline \& at least one post baseline CGI overall illness measurement.~Baseline for extension phase is defined as the last non-missing value in acute phase.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine - Acute | Change From Baseline in Clinical Global Impression (CGI) Severity: Overall Illness Score | -0.67 units on a scale | Standard Error 0.125 |
| Placebo - Acute | Change From Baseline in Clinical Global Impression (CGI) Severity: Overall Illness Score | -0.67 units on a scale | Standard Error 0.121 |
Secondary
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.
Time frame: Baseline, 13 weeks
Population: All randomized participants who received at least one dose of study drug and had baseline \& at least one post baseline CGI-S overall illness score.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine - Acute | Change From Baseline in Clinical Global Impression (CGI) Severity: Overall Illness Score | -0.88 units on a scale | Standard Error 0.121 |
| Placebo - Acute | Change From Baseline in Clinical Global Impression (CGI) Severity: Overall Illness Score | -0.66 units on a scale | Standard Error 0.118 |
p-value: 0.14695% CI: [-0.52, 0.08]ANCOVA
Secondary
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.
Time frame: Baseline (extension phase), 39 weeks
Population: All randomized participants who received at least one dose of study drug \& had baseline \& at least one post baseline FDI-child measurement.~Baseline for extension phase is defined as the last non-missing value in acute phase.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine - Acute | Change From Baseline in Functional Disability Inventory Child Form (FDI-child) | -1.71 units on a scale | Standard Error 1.202 |
| Placebo - Acute | Change From Baseline in Functional Disability Inventory Child Form (FDI-child) | -1.03 units on a scale | Standard Error 1.267 |
Secondary
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.
Time frame: Baseline, 13 weeks
Population: All randomized participants who received at least one dose of study drug and had baseline \& at least one post baseline FDI child scale score.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine - Acute | Change From Baseline in Functional Disability Inventory Child Form (FDI-Child) | -3.97 units on a scale | Standard Error 1.038 |
| Placebo - Acute | Change From Baseline in Functional Disability Inventory Child Form (FDI-Child) | -5.00 units on a scale | Standard Error 1.021 |
p-value: 0.43195% CI: [-1.54, 3.59]ANCOVA
Secondary
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.
Time frame: Baseline (extension phase), 39 weeks
Population: All randomized participants who received at least one dose of study drug \& had baseline \& at least one post baseline FDI-parent measurement.~Baseline for extension phase is defined as the last non-missing value in acute phase.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine - Acute | Change From Baseline in Functional Disability Inventory Parent Form (FDI-parent) | -3.49 units on a scale | Standard Error 1.227 |
| Placebo - Acute | Change From Baseline in Functional Disability Inventory Parent Form (FDI-parent) | -2.27 units on a scale | Standard Error 1.327 |
Secondary
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.
Time frame: Baseline, 13 weeks
Population: All randomized participants who received at least one dose of study drug and had baseline \& at least one post baseline FDI-parent scale score.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine - Acute | Change From Baseline in Functional Disability Inventory Parent Form (FDI-Parent) | -3.25 units on a scale | Standard Error 1.152 |
| Placebo - Acute | Change From Baseline in Functional Disability Inventory Parent Form (FDI-Parent) | -4.17 units on a scale | Standard Error 1.139 |
p-value: 0.52995% CI: [-1.95, 3.79]ANCOVA
Secondary
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.
Time frame: Baseline, 13 weeks
Population: All randomized participants who received at least one dose of study drug and had baseline \& at least one post baseline MASC score.~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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine - Acute | Change From Baseline in Multidimensional Anxiety Scale for Children (MASC) | Harm Avoidance | -1.34 units on a scale | Standard Error 0.507 |
| Duloxetine - Acute | Change From Baseline in Multidimensional Anxiety Scale for Children (MASC) | Separation/Panic | -1.62 units on a scale | Standard Error 0.393 |
| Duloxetine - Acute | Change From Baseline in Multidimensional Anxiety Scale for Children (MASC) | Social Anxiety | -1.86 units on a scale | Standard Error 0.497 |
| Duloxetine - Acute | Change From Baseline in Multidimensional Anxiety Scale for Children (MASC) | Total Score | -6.21 units on a scale | Standard Error 1.575 |
| Duloxetine - Acute | Change From Baseline in Multidimensional Anxiety Scale for Children (MASC) | Physical Symptoms | -1.39 units on a scale | Standard Error 0.663 |
| Placebo - Acute | Change From Baseline in Multidimensional Anxiety Scale for Children (MASC) | Total Score | -4.99 units on a scale | Standard Error 1.558 |
| Placebo - Acute | Change From Baseline in Multidimensional Anxiety Scale for Children (MASC) | Physical Symptoms | -1.44 units on a scale | Standard Error 0.652 |
| Placebo - Acute | Change From Baseline in Multidimensional Anxiety Scale for Children (MASC) | Harm Avoidance | -0.78 units on a scale | Standard Error 0.501 |
| Placebo - Acute | Change From Baseline in Multidimensional Anxiety Scale for Children (MASC) | Social Anxiety | -1.42 units on a scale | Standard Error 0.489 |
| Placebo - Acute | Change From Baseline in Multidimensional Anxiety Scale for Children (MASC) | Separation/Panic | -1.43 units on a scale | Standard Error 0.389 |
Comparison: Physical Symptoms Scorep-value: 0.95595% CI: [-1.59, 1.68]ANCOVA
Comparison: Harm Avoidancep-value: 0.38195% CI: [-1.82, 0.7]ANCOVA
Comparison: Social Anxietyp-value: 0.48695% CI: [-1.66, 0.79]ANCOVA
Comparison: Separation/Panicp-value: 0.795% CI: [-1.17, 0.79]ANCOVA
Comparison: Total Scorep-value: 0.5495% CI: [-5.12, 2.69]ANCOVA
Secondary
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.
Time frame: Baseline (extension phase), 39 weeks
Population: All randomized participants who received at least one dose of study drug \& had baseline \& at least one post baseline MASC measurement.~Baseline for extension phase is defined as the last non-missing value in acute phase.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine - Acute | Change From Baseline in Multidimensional Anxiety Scale for Children (MASC) | Harm Avoidance | 0.23 units on a scale | Standard Error 0.485 |
| Duloxetine - Acute | Change From Baseline in Multidimensional Anxiety Scale for Children (MASC) | Separation/Panic | -0.06 units on a scale | Standard Error 0.371 |
| Duloxetine - Acute | Change From Baseline in Multidimensional Anxiety Scale for Children (MASC) | Social Anxiety | -0.11 units on a scale | Standard Error 0.487 |
| Duloxetine - Acute | Change From Baseline in Multidimensional Anxiety Scale for Children (MASC) | Total Score | -0.55 units on a scale | Standard Error 1.478 |
| Duloxetine - Acute | Change From Baseline in Multidimensional Anxiety Scale for Children (MASC) | Physical Symptoms | -0.63 units on a scale | Standard Error 0.715 |
| Placebo - Acute | Change From Baseline in Multidimensional Anxiety Scale for Children (MASC) | Total Score | -0.78 units on a scale | Standard Error 1.432 |
| Placebo - Acute | Change From Baseline in Multidimensional Anxiety Scale for Children (MASC) | Physical Symptoms | -0.92 units on a scale | Standard Error 0.692 |
| Placebo - Acute | Change From Baseline in Multidimensional Anxiety Scale for Children (MASC) | Harm Avoidance | 0.10 units on a scale | Standard Error 0.471 |
| Placebo - Acute | Change From Baseline in Multidimensional Anxiety Scale for Children (MASC) | Social Anxiety | -0.02 units on a scale | Standard Error 0.472 |
| Placebo - Acute | Change From Baseline in Multidimensional Anxiety Scale for Children (MASC) | Separation/Panic | 0.01 units on a scale | Standard Error 0.361 |
Secondary
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.
Time frame: Baseline (extension phase), 39 weeks
Population: All randomized participants who received at least one dose of study drug \& had baseline \& at least one post baseline PPQ measurement.~Baseline for extension phase is defined as the last non-missing value in acute phase.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine - Acute | Change From Baseline in Pediatric Pain Questionnaire (PPQ) Item Scores | Average Pain Score | -10.65 units on a scale | Standard Error 3.08 |
| Duloxetine - Acute | Change From Baseline in Pediatric Pain Questionnaire (PPQ) Item Scores | Worst Pain Score | -4.15 units on a scale | Standard Error 3.127 |
| Duloxetine - Acute | Change From Baseline in Pediatric Pain Questionnaire (PPQ) Item Scores | Score Right Now | -4.74 units on a scale | Standard Error 3.075 |
| Placebo - Acute | Change From Baseline in Pediatric Pain Questionnaire (PPQ) Item Scores | Average Pain Score | -6.44 units on a scale | Standard Error 3.296 |
| Placebo - Acute | Change From Baseline in Pediatric Pain Questionnaire (PPQ) Item Scores | Worst Pain Score | -8.06 units on a scale | Standard Error 3.677 |
| Placebo - Acute | Change From Baseline in Pediatric Pain Questionnaire (PPQ) Item Scores | Score Right Now | -6.34 units on a scale | Standard Error 3.335 |
Secondary
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.
Time frame: Baseline, 13 weeks
Population: All randomized participants who received at least one dose of study drug and had baseline \& at least one post baseline PPQ score.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine - Acute | Change From Baseline in Pediatric Pain Questionnaire (PPQ) Item Scores | Average Pain Score | -11.03 mm | Standard Error 2.982 |
| Duloxetine - Acute | Change From Baseline in Pediatric Pain Questionnaire (PPQ) Item Scores | Worst Pain Score | -14.36 mm | Standard Error 3.367 |
| Duloxetine - Acute | Change From Baseline in Pediatric Pain Questionnaire (PPQ) Item Scores | Pain Score Right Now | -8.99 mm | Standard Error 3.092 |
| Placebo - Acute | Change From Baseline in Pediatric Pain Questionnaire (PPQ) Item Scores | Average Pain Score | -9.41 mm | Standard Error 2.946 |
| Placebo - Acute | Change From Baseline in Pediatric Pain Questionnaire (PPQ) Item Scores | Worst Pain Score | -8.46 mm | Standard Error 3.322 |
| Placebo - Acute | Change From Baseline in Pediatric Pain Questionnaire (PPQ) Item Scores | Pain Score Right Now | -7.20 mm | Standard Error 3.065 |
Comparison: Average Pain Scorep-value: 0.66995% CI: [-9.1, 5.86]ANCOVA
Comparison: Worst Pain Scorep-value: 0.16995% CI: [-14.32, 2.53]ANCOVA
Comparison: Pain Score Right Nowp-value: 0.64795% CI: [-9.53, 5.94]ANCOVA
Secondary
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.
Time frame: Baseline, 13 weeks
Population: All randomized participants who received at least one dose of study drug and had baseline \& at least one post baseline BPI severity \& interferences items score.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine - Acute | Change From Baseline to 13 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-Adolescent Version Severity and Interference Items | General Activity | -2.00 units on a scale | Standard Error 0.262 |
| Duloxetine - Acute | Change From Baseline to 13 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-Adolescent Version Severity and Interference Items | Normal Work | -1.49 units on a scale | Standard Error 0.277 |
| Duloxetine - Acute | Change From Baseline to 13 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-Adolescent Version Severity and Interference Items | Pain Right Now | -1.56 units on a scale | Standard Error 0.274 |
| Duloxetine - Acute | Change From Baseline to 13 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-Adolescent Version Severity and Interference Items | Relations With Other People | -1.87 units on a scale | Standard Error 0.237 |
| Duloxetine - Acute | Change From Baseline to 13 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-Adolescent Version Severity and Interference Items | Mood | -2.00 units on a scale | Standard Error 0.269 |
| Duloxetine - Acute | Change From Baseline to 13 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-Adolescent Version Severity and Interference Items | Sleep | -1.40 units on a scale | Standard Error 0.343 |
| Duloxetine - Acute | Change From Baseline to 13 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-Adolescent Version Severity and Interference Items | Least Pain | -1.08 units on a scale | Standard Error 0.239 |
| Duloxetine - Acute | Change From Baseline to 13 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-Adolescent Version Severity and Interference Items | Enjoyment of Life | -1.76 units on a scale | Standard Error 0.253 |
| Duloxetine - Acute | Change From Baseline to 13 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-Adolescent Version Severity and Interference Items | Walking ability | -1.30 units on a scale | Standard Error 0.266 |
| Duloxetine - Acute | Change From Baseline to 13 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-Adolescent Version Severity and Interference Items | School Work | -1.68 units on a scale | Standard Error 0.316 |
| Duloxetine - Acute | Change From Baseline to 13 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-Adolescent Version Severity and Interference Items | Worst Pain | -1.58 units on a scale | Standard Error 0.27 |
| Placebo - Acute | Change From Baseline to 13 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-Adolescent Version Severity and Interference Items | School Work | -1.08 units on a scale | Standard Error 0.313 |
| Placebo - Acute | Change From Baseline to 13 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-Adolescent Version Severity and Interference Items | Worst Pain | -0.90 units on a scale | Standard Error 0.266 |
| Placebo - Acute | Change From Baseline to 13 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-Adolescent Version Severity and Interference Items | Least Pain | -0.47 units on a scale | Standard Error 0.236 |
| Placebo - Acute | Change From Baseline to 13 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-Adolescent Version Severity and Interference Items | Pain Right Now | -1.05 units on a scale | Standard Error 0.271 |
| Placebo - Acute | Change From Baseline to 13 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-Adolescent Version Severity and Interference Items | General Activity | -1.03 units on a scale | Standard Error 0.258 |
| Placebo - Acute | Change From Baseline to 13 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-Adolescent Version Severity and Interference Items | Mood | -1.46 units on a scale | Standard Error 0.265 |
| Placebo - Acute | Change From Baseline to 13 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-Adolescent Version Severity and Interference Items | Walking ability | -1.09 units on a scale | Standard Error 0.262 |
| Placebo - Acute | Change From Baseline to 13 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-Adolescent Version Severity and Interference Items | Normal Work | -1.21 units on a scale | Standard Error 0.274 |
| Placebo - Acute | Change From Baseline to 13 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-Adolescent Version Severity and Interference Items | Relations With Other People | -1.07 units on a scale | Standard Error 0.233 |
| Placebo - Acute | Change From Baseline to 13 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-Adolescent Version Severity and Interference Items | Sleep | -1.05 units on a scale | Standard Error 0.338 |
| Placebo - Acute | Change From Baseline to 13 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-Adolescent Version Severity and Interference Items | Enjoyment of Life | -1.47 units on a scale | Standard Error 0.25 |
Comparison: Worst Painp-value: 0.05995% CI: [-1.4, 0.03]Mixed Models Analysis
Comparison: Least Painp-value: 0.05995% CI: [-1.24, 0.02]Mixed Models Analysis
Comparison: Pain Right Nowp-value: 0.16595% CI: [-1.23, 0.21]Mixed Models Analysis
Comparison: General Activityp-value: 0.00595% CI: [-1.65, -0.3]Mixed Models Analysis
Comparison: Moodp-value: 0.12895% CI: [-1.25, 0.16]Mixed Models Analysis
Comparison: Walking abilityp-value: 0.5695% CI: [-0.9, 0.49]Mixed Models Analysis
Comparison: Normal Workp-value: 0.44895% CI: [-1.01, 0.45]Mixed Models Analysis
Comparison: Relations With Otherp-value: 0.01195% CI: [-1.42, -0.19]Mixed Models Analysis
Comparison: Sleepp-value: 0.44395% CI: [-1.25, 0.55]Mixed Models Analysis
Comparison: Enjoyment of Lifep-value: 0.3995% CI: [-0.96, 0.38]Mixed Models Analysis
Comparison: School Workp-value: 0.1695% CI: [-1.44, 0.24]Mixed Models Analysis
Secondary
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.
Time frame: Baseline (extension phase), 39 weeks
Population: All randomized participants who received at least one dose of study drug \& had baseline \& at least one post baseline BPI severity \& interferences items scores.~Baseline for extension phase is defined as the last non-missing value in acute phase.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine - Acute | Change From Baseline to 39 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-adolescent Version Severity and Interference Items | General Activity | -0.18 units on a scale | Standard Error 0.233 |
| Duloxetine - Acute | Change From Baseline to 39 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-adolescent Version Severity and Interference Items | Normal Work | -0.62 units on a scale | Standard Error 0.231 |
| Duloxetine - Acute | Change From Baseline to 39 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-adolescent Version Severity and Interference Items | Pain Right Now | -0.38 units on a scale | Standard Error 0.259 |
| Duloxetine - Acute | Change From Baseline to 39 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-adolescent Version Severity and Interference Items | Relations with Other People | -0.12 units on a scale | Standard Error 0.229 |
| Duloxetine - Acute | Change From Baseline to 39 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-adolescent Version Severity and Interference Items | Mood | -0.15 units on a scale | Standard Error 0.27 |
| Duloxetine - Acute | Change From Baseline to 39 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-adolescent Version Severity and Interference Items | Sleep | -0.63 units on a scale | Standard Error 0.292 |
| Duloxetine - Acute | Change From Baseline to 39 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-adolescent Version Severity and Interference Items | Least Pain | -0.29 units on a scale | Standard Error 0.218 |
| Duloxetine - Acute | Change From Baseline to 39 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-adolescent Version Severity and Interference Items | Enjoyment of Life | -0.25 units on a scale | Standard Error 0.243 |
| Duloxetine - Acute | Change From Baseline to 39 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-adolescent Version Severity and Interference Items | Walking Ability | -0.24 units on a scale | Standard Error 0.26 |
| Duloxetine - Acute | Change From Baseline to 39 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-adolescent Version Severity and Interference Items | School Work | -0.59 units on a scale | Standard Error 0.278 |
| Duloxetine - Acute | Change From Baseline to 39 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-adolescent Version Severity and Interference Items | Worst Pain | -0.65 units on a scale | Standard Error 0.262 |
| Placebo - Acute | Change From Baseline to 39 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-adolescent Version Severity and Interference Items | School Work | -0.06 units on a scale | Standard Error 0.271 |
| Placebo - Acute | Change From Baseline to 39 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-adolescent Version Severity and Interference Items | Worst Pain | -0.80 units on a scale | Standard Error 0.256 |
| Placebo - Acute | Change From Baseline to 39 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-adolescent Version Severity and Interference Items | Least Pain | -0.45 units on a scale | Standard Error 0.212 |
| Placebo - Acute | Change From Baseline to 39 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-adolescent Version Severity and Interference Items | Pain Right Now | -0.29 units on a scale | Standard Error 0.252 |
| Placebo - Acute | Change From Baseline to 39 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-adolescent Version Severity and Interference Items | General Activity | 0.20 units on a scale | Standard Error 0.229 |
| Placebo - Acute | Change From Baseline to 39 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-adolescent Version Severity and Interference Items | Mood | -0.25 units on a scale | Standard Error 0.258 |
| Placebo - Acute | Change From Baseline to 39 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-adolescent Version Severity and Interference Items | Walking Ability | -0.21 units on a scale | Standard Error 0.253 |
| Placebo - Acute | Change From Baseline to 39 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-adolescent Version Severity and Interference Items | Normal Work | -0.32 units on a scale | Standard Error 0.226 |
| Placebo - Acute | Change From Baseline to 39 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-adolescent Version Severity and Interference Items | Relations with Other People | -0.41 units on a scale | Standard Error 0.222 |
| Placebo - Acute | Change From Baseline to 39 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-adolescent Version Severity and Interference Items | Sleep | -0.54 units on a scale | Standard Error 0.284 |
| Placebo - Acute | Change From Baseline to 39 Week Endpoint in Brief Pain Inventory (BPI) Modified Short Form-adolescent Version Severity and Interference Items | Enjoyment of Life | -0.26 units on a scale | Standard Error 0.236 |
Secondary
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.
Time frame: Baseline (Extension Phase), 39 weeks
Population: All randomized participants in duloxetine only arm with ≥30% pain reduction from baseline on the BPI average pain severity measure at the last non-missing assessment in acute phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine - Acute | Maintenance Effect in Acute Phase Responders on the Brief Pain Inventory (BPI) Modified Short Form-adolescent Version 24 Hour Average Pain Severity Item | -3.4 units on a scale | Standard Deviation 1.24 |
Secondary
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).
Time frame: 13 weeks
Population: All randomized participants who received at least one dose of study drug and had baseline \& at least one post baseline BPI average pain score.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Duloxetine - Acute | Number of Participants With Greater Than or Equal to 30% Reduction From Baseline in BPI 24 Hour Average Pain Severity Score at 13 Weeks | 47 Participants |
| Placebo - Acute | Number of Participants With Greater Than or Equal to 30% Reduction From Baseline in BPI 24 Hour Average Pain Severity Score at 13 Weeks | 33 Participants |
p-value: 0.051Fisher Exact
Secondary
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).
Time frame: 13 weeks
Population: All randomized participants who received at least one dose of study drug and had baseline \& at least one post baseline BPI average pain score.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Duloxetine - Acute | Number of Participants With Greater Than or Equal to 50% Reduction From Baseline in BPI 24 Hour Average Pain Severity Score at 13 Weeks | 36 Participants |
| Placebo - Acute | Number of Participants With Greater Than or Equal to 50% Reduction From Baseline in BPI 24 Hour Average Pain Severity Score at 13 Weeks | 22 Participants |
p-value: 0.038Fisher Exact