Trial Outcomes & Findings for A Study of Duloxetine in Adolescents With Juvenile Primary Fibromyalgia Syndrome (NCT NCT01237587)

Last Updated: 2019-09-20

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

184 participants

Primary outcome timeframe

Baseline, 13 weeks

Results posted on

2019-09-20

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Duloxetine/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.	Placebo/Duloxetine 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 during1-week tapering phase.
Double Blind Treatment (Acute Phase) STARTED	91	93
Double Blind Treatment (Acute Phase) Received at Least One Dose of Study Drug	91	93
Double Blind Treatment (Acute Phase) COMPLETED	74	75
Double Blind Treatment (Acute Phase) NOT COMPLETED	17	18
Open Label Treatment (Extension Phase) STARTED	74	75
Open Label Treatment (Extension Phase) Received at Least One Dose of Study Drug	74	75
Open Label Treatment (Extension Phase) COMPLETED	56	50
Open Label Treatment (Extension Phase) NOT COMPLETED	18	25
Taper Phase STARTED	36	44
Taper Phase COMPLETED	31	34
Taper Phase NOT COMPLETED	5	10

Reasons for withdrawal

Reasons for withdrawal
Measure	Duloxetine/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.	Placebo/Duloxetine 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 during1-week tapering phase.
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) Lost to Follow-up	4	3
Open Label Treatment (Extension Phase) Adverse Event	5	5
Open Label Treatment (Extension Phase) Lack of Efficacy	2	4
Open Label Treatment (Extension Phase) Parent/Guardian Decision	2	4
Open Label Treatment (Extension Phase) Withdrawal by Subject	0	5
Open Label Treatment (Extension Phase) Sponsor Decision	1	0
Open Label Treatment (Extension Phase) Physician Decision	4	4
Taper Phase Adverse Event	0	2
Taper Phase Protocol Violation	2	0
Taper Phase Lack of Efficacy	2	5
Taper Phase Parent/Guardian Decision	0	2
Taper Phase Sponsor Decision	1	0
Taper Phase Withdrawal by Subject	0	1

Baseline Characteristics

All randomized participants who had baseline BPI score.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Duloxetine n=91 Participants 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.	Placebo n=93 Participants 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.	Total n=184 Participants Total of all reporting groups
Age, Continuous	15.74 years STANDARD_DEVIATION 1.379 • n=91 Participants	15.33 years STANDARD_DEVIATION 1.421 • n=93 Participants	15.53 years STANDARD_DEVIATION 1.411 • n=184 Participants
Sex: Female, Male Female	73 Participants n=91 Participants	65 Participants n=93 Participants	138 Participants n=184 Participants
Sex: Female, Male Male	18 Participants n=91 Participants	28 Participants n=93 Participants	46 Participants n=184 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	36 Participants n=91 Participants	39 Participants n=93 Participants	75 Participants n=184 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	54 Participants n=91 Participants	54 Participants n=93 Participants	108 Participants n=184 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=91 Participants	0 Participants n=93 Participants	1 Participants n=184 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=91 Participants	0 Participants n=93 Participants	1 Participants n=184 Participants
Race (NIH/OMB) Asian	6 Participants n=91 Participants	7 Participants n=93 Participants	13 Participants n=184 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=91 Participants	1 Participants n=93 Participants	1 Participants n=184 Participants
Race (NIH/OMB) Black or African American	7 Participants n=91 Participants	8 Participants n=93 Participants	15 Participants n=184 Participants
Race (NIH/OMB) White	72 Participants n=91 Participants	70 Participants n=93 Participants	142 Participants n=184 Participants
Race (NIH/OMB) More than one race	4 Participants n=91 Participants	6 Participants n=93 Participants	10 Participants n=184 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=91 Participants	1 Participants n=93 Participants	2 Participants n=184 Participants
Region of Enrollment Puerto Rico	2 Participants n=91 Participants	3 Participants n=93 Participants	5 Participants n=184 Participants
Region of Enrollment Argentina	19 Participants n=91 Participants	19 Participants n=93 Participants	38 Participants n=184 Participants
Region of Enrollment United States	64 Participants n=91 Participants	64 Participants n=93 Participants	128 Participants n=184 Participants
Region of Enrollment India	6 Participants n=91 Participants	7 Participants n=93 Participants	13 Participants n=184 Participants
Brief Pain Inventory (BPI) Modified short form (SF) Adolescent version (AV) Average Pain	5.7 units on a scale STANDARD_DEVIATION 1.37 • n=90 Participants • All randomized participants who had baseline BPI score.	5.6 units on a scale STANDARD_DEVIATION 1.55 • n=91 Participants • All randomized participants who had baseline BPI score.	5.65 units on a scale STANDARD_DEVIATION 1.46 • n=181 Participants • All randomized participants who had baseline BPI score.
Brief Pain Inventory (BPI) Modified short form (SF) Adolescent version (AV) Worst Pain	7.1 units on a scale STANDARD_DEVIATION 1.8 • n=91 Participants • All randomized participants who had baseline BPI score.	6.9 units on a scale STANDARD_DEVIATION 1.9 • n=93 Participants • All randomized participants who had baseline BPI score.	7.0 units on a scale STANDARD_DEVIATION 1.9 • n=184 Participants • All randomized participants who had baseline BPI score.
Brief Pain Inventory (BPI) Modified short form (SF) Adolescent version (AV) Least Pain	3.7 units on a scale STANDARD_DEVIATION 2.1 • n=91 Participants • All randomized participants who had baseline BPI score.	3.8 units on a scale STANDARD_DEVIATION 2.0 • n=93 Participants • All randomized participants who had baseline BPI score.	3.8 units on a scale STANDARD_DEVIATION 2.1 • n=184 Participants • All randomized participants who had baseline BPI score.
Brief Pain Inventory (BPI) Modified short form (SF) Adolescent version (AV) Pain Right Now	5.2 units on a scale STANDARD_DEVIATION 2.4 • n=91 Participants • All randomized participants who had baseline BPI score.	5.2 units on a scale STANDARD_DEVIATION 2.3 • n=93 Participants • All randomized participants who had baseline BPI score.	5.2 units on a scale STANDARD_DEVIATION 2.4 • n=184 Participants • All randomized participants who had baseline BPI score.
Brief Pain Inventory (BPI) Modified short form (SF) Adolescent version (AV) General Activity	5.2 units on a scale STANDARD_DEVIATION 2.0 • n=91 Participants • All randomized participants who had baseline BPI score.	5.1 units on a scale STANDARD_DEVIATION 2.0 • n=93 Participants • All randomized participants who had baseline BPI score.	5.2 units on a scale STANDARD_DEVIATION 2.3 • n=184 Participants • All randomized participants who had baseline BPI score.
Brief Pain Inventory (BPI) Modified short form (SF) Adolescent version (AV) Mood	4.9 units on a scale STANDARD_DEVIATION 2.6 • n=91 Participants • All randomized participants who had baseline BPI score.	5.0 units on a scale STANDARD_DEVIATION 2.6 • n=93 Participants • All randomized participants who had baseline BPI score.	5.0 units on a scale STANDARD_DEVIATION 2.6 • n=184 Participants • All randomized participants who had baseline BPI score.
Brief Pain Inventory (BPI) Modified short form (SF) Adolescent version (AV) Walking Ability	4.1 units on a scale STANDARD_DEVIATION 2.8 • n=91 Participants • All randomized participants who had baseline BPI score.	4.5 units on a scale STANDARD_DEVIATION 2.8 • n=93 Participants • All randomized participants who had baseline BPI score.	4.3 units on a scale STANDARD_DEVIATION 2.8 • n=184 Participants • All randomized participants who had baseline BPI score.
Brief Pain Inventory (BPI) Modified short form (SF) Adolescent version (AV) Normal Work	4.6 units on a scale STANDARD_DEVIATION 2.6 • n=91 Participants • All randomized participants who had baseline BPI score.	4.9 units on a scale STANDARD_DEVIATION 2.5 • n=93 Participants • All randomized participants who had baseline BPI score.	4.8 units on a scale STANDARD_DEVIATION 2.6 • n=184 Participants • All randomized participants who had baseline BPI score.
Brief Pain Inventory (BPI) Modified short form (SF) Adolescent version (AV) Relations with other people	3.7 units on a scale STANDARD_DEVIATION 2.7 • n=91 Participants • All randomized participants who had baseline BPI score.	3.7 units on a scale STANDARD_DEVIATION 2.8 • n=93 Participants • All randomized participants who had baseline BPI score.	3.7 units on a scale STANDARD_DEVIATION 2.8 • n=184 Participants • All randomized participants who had baseline BPI score.
Brief Pain Inventory (BPI) Modified short form (SF) Adolescent version (AV) Sleep	5.9 units on a scale STANDARD_DEVIATION 2.8 • n=91 Participants • All randomized participants who had baseline BPI score.	5.5 units on a scale STANDARD_DEVIATION 3.0 • n=93 Participants • All randomized participants who had baseline BPI score.	5.7 units on a scale STANDARD_DEVIATION 2.9 • n=184 Participants • All randomized participants who had baseline BPI score.
Brief Pain Inventory (BPI) Modified short form (SF) Adolescent version (AV) Enjoyment of Life	4.1 units on a scale STANDARD_DEVIATION 3.1 • n=91 Participants • All randomized participants who had baseline BPI score.	4.3 units on a scale STANDARD_DEVIATION 2.8 • n=93 Participants • All randomized participants who had baseline BPI score.	4.2 units on a scale STANDARD_DEVIATION 3.0 • n=184 Participants • All randomized participants who had baseline BPI score.
Brief Pain Inventory (BPI) Modified short form (SF) Adolescent version (AV) School Work	4.8 units on a scale STANDARD_DEVIATION 3.0 • n=91 Participants • All randomized participants who had baseline BPI score.	4.3 units on a scale STANDARD_DEVIATION 3.2 • n=93 Participants • All randomized participants who had baseline BPI score.	4.6 units on a scale STANDARD_DEVIATION 3.1 • n=184 Participants • All randomized participants who had baseline BPI score.
Pediatric Pain Questionnaire (PPQ) Average Pain	61.8 mm STANDARD_DEVIATION 19.5 • n=87 Participants • All randomized participants who had baseline PPQ score.	58.1 mm STANDARD_DEVIATION 22.3 • n=86 Participants • All randomized participants who had baseline PPQ score.	58.94 mm STANDARD_DEVIATION 20.9 • n=173 Participants • All randomized participants who had baseline PPQ score.
Pediatric Pain Questionnaire (PPQ) Worst Pain	77.4 mm STANDARD_DEVIATION 20.3 • n=87 Participants • All randomized participants who had baseline PPQ score.	75.5 mm STANDARD_DEVIATION 20.4 • n=86 Participants • All randomized participants who had baseline PPQ score.	76.5 mm STANDARD_DEVIATION 20.4 • n=173 Participants • All randomized participants who had baseline PPQ score.
Pediatric Pain Questionnaire (PPQ) pain now	50.1 mm STANDARD_DEVIATION 27.5 • n=87 Participants • All randomized participants who had baseline PPQ score.	52.0 mm STANDARD_DEVIATION 25.2 • n=86 Participants • All randomized participants who had baseline PPQ score.	51.0 mm STANDARD_DEVIATION 26.4 • n=173 Participants • All randomized participants who had baseline PPQ score.
Clinical Global Impression (CGI) Severity: Mental Illness	2.1 units on a scale STANDARD_DEVIATION 1.2 • n=90 Participants • All randomized participants who had baseline CGI mental illness score.	2.0 units on a scale STANDARD_DEVIATION 1.1 • n=92 Participants • All randomized participants who had baseline CGI mental illness score.	2.05 units on a scale STANDARD_DEVIATION 1.15 • n=182 Participants • All randomized participants who had baseline CGI mental illness score.
Clinical Global Impression (CGI) Severity: Overall Illness	4.1 units on a scale STANDARD_DEVIATION 0.9 • n=90 Participants • All randomized participants who had baseline CGI overall illness score.	4.1 units on a scale STANDARD_DEVIATION 0.8 • n=92 Participants • All randomized participants who had baseline CGI overall illness score.	4.1 units on a scale STANDARD_DEVIATION 0.9 • n=182 Participants • All randomized participants who had baseline CGI overall illness score.
Functional Disability Inventory (FDI) Child score	23.3 units on a scale STANDARD_DEVIATION 11.1 • n=87 Participants • All randomized participants who had baseline FDI child score.	22.3 units on a scale STANDARD_DEVIATION 9.9 • n=88 Participants • All randomized participants who had baseline FDI child score.	22.8 units on a scale STANDARD_DEVIATION 10.5 • n=175 Participants • All randomized participants who had baseline FDI child score.
Functional Disability Inventory (FDI) Parent Score	22.4 units on a scale STANDARD_DEVIATION 11.4 • n=86 Participants • All randomized participants who had baseline FDI parent score.	22.3 units on a scale STANDARD_DEVIATION 10.7 • n=87 Participants • All randomized participants who had baseline FDI parent score.	22.4 units on a scale STANDARD_DEVIATION 11.1 • n=173 Participants • All randomized participants who had baseline FDI parent score.
Children's Depression Inventory (CDI)	13.5 units on a scale STANDARD_DEVIATION 7.1 • n=89 Participants • All randomized participants who had baseline CDI score.	13.1 units on a scale STANDARD_DEVIATION 7.7 • n=89 Participants • All randomized participants who had baseline CDI score.	13.3 units on a scale STANDARD_DEVIATION 7.4 • n=178 Participants • All randomized participants who had baseline CDI score.
Multidimensional Anxiety Scale for Children (MASC) Physical Symptoms	13.6 units on a scale STANDARD_DEVIATION 7.3 • n=89 Participants • All randomized participants who had baseline MASC score.	13.6 units on a scale STANDARD_DEVIATION 7.6 • n=89 Participants • All randomized participants who had baseline MASC score.	13.6 units on a scale STANDARD_DEVIATION 7.5 • n=178 Participants • All randomized participants who had baseline MASC score.
Multidimensional Anxiety Scale for Children (MASC) Harm Avoidance	15.0 units on a scale STANDARD_DEVIATION 4.2 • n=89 Participants • All randomized participants who had baseline MASC score.	14.4 units on a scale STANDARD_DEVIATION 4.7 • n=89 Participants • All randomized participants who had baseline MASC score.	14.7 units on a scale STANDARD_DEVIATION 4.5 • n=178 Participants • All randomized participants who had baseline MASC score.
Multidimensional Anxiety Scale for Children (MASC) Social Anxiety	9.8 units on a scale STANDARD_DEVIATION 6.3 • n=89 Participants • All randomized participants who had baseline MASC score.	9.8 units on a scale STANDARD_DEVIATION 6.3 • n=89 Participants • All randomized participants who had baseline MASC score.	9.8 units on a scale STANDARD_DEVIATION 6.6 • n=178 Participants • All randomized participants who had baseline MASC score.
Multidimensional Anxiety Scale for Children (MASC) Separation/Panic	6.7 units on a scale STANDARD_DEVIATION 4.9 • n=89 Participants • All randomized participants who had baseline MASC score.	6.0 units on a scale STANDARD_DEVIATION 4.5 • n=89 Participants • All randomized participants who had baseline MASC score.	6.4 units on a scale STANDARD_DEVIATION 4.7 • n=178 Participants • All randomized participants who had baseline MASC score.
Multidimensional Anxiety Scale for Children (MASC) Total Score	45.1 units on a scale STANDARD_DEVIATION 16.6 • n=89 Participants • All randomized participants who had baseline MASC score.	43.9 units on a scale STANDARD_DEVIATION 18.7 • n=89 Participants • All randomized participants who had baseline MASC score.	44.5 units on a scale STANDARD_DEVIATION 17.65 • n=178 Participants • All randomized participants who had baseline MASC score.

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Duloxetine - Acute n=76 Participants Participants received 30 or 60 mg Duloxetine orally once daily (QD) for 13 weeks.	Placebo - Acute n=76 Participants Participants received Placebo orally once daily (QD) for 13 weeks.
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	-0.97 units on a scale Standard Error 0.244

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Duloxetine - Acute n=76 Participants Participants received 30 or 60 mg Duloxetine orally once daily (QD) for 13 weeks.	Placebo - Acute n=76 Participants Participants received Placebo orally once daily (QD) for 13 weeks.
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 0.270	-0.90 units on a scale Standard Error 0.266
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	-0.47 units on a scale Standard Error 0.236
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	-1.05 units on a scale Standard Error 0.271
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	-1.03 units on a scale Standard Error 0.258
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	-1.46 units on a scale Standard Error 0.265
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	-1.09 units on a scale Standard Error 0.262
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	-1.21 units on a scale Standard Error 0.274
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	-1.07 units on a scale Standard Error 0.233
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	-1.05 units on a scale Standard Error 0.338
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	-1.47 units on a scale Standard Error 0.250
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	-1.08 units on a scale Standard Error 0.313

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Duloxetine - Acute n=44 Participants Participants received 30 or 60 mg Duloxetine orally once daily (QD) for 13 weeks.	Placebo - Acute Participants received Placebo orally once daily (QD) for 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	-3.4 units on a scale Standard Deviation 1.24	—

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	Duloxetine - Acute n=90 Participants Participants received 30 or 60 mg Duloxetine orally once daily (QD) for 13 weeks.	Placebo - Acute n=91 Participants Participants received Placebo orally once daily (QD) for 13 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	47 Participants	33 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Duloxetine - Acute n=90 Participants Participants received 30 or 60 mg Duloxetine orally once daily (QD) for 13 weeks.	Placebo - Acute n=91 Participants Participants received Placebo orally once daily (QD) for 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	36 Participants	22 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Duloxetine - Acute n=87 Participants Participants received 30 or 60 mg Duloxetine orally once daily (QD) for 13 weeks.	Placebo - Acute n=86 Participants Participants received Placebo orally once daily (QD) for 13 weeks.
Change From Baseline in Pediatric Pain Questionnaire (PPQ) Item Scores Average Pain Score	-11.03 mm Standard Error 2.982	-9.41 mm Standard Error 2.946
Change From Baseline in Pediatric Pain Questionnaire (PPQ) Item Scores Worst Pain Score	-14.36 mm Standard Error 3.367	-8.46 mm Standard Error 3.322
Change From Baseline in Pediatric Pain Questionnaire (PPQ) Item Scores Pain Score Right Now	-8.99 mm Standard Error 3.092	-7.20 mm Standard Error 3.065

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Duloxetine - Acute n=90 Participants Participants received 30 or 60 mg Duloxetine orally once daily (QD) for 13 weeks.	Placebo - Acute n=92 Participants Participants received Placebo orally once daily (QD) for 13 weeks.
Change From Baseline in Clinical Global Impression (CGI) Severity: Overall Illness Score	-0.88 units on a scale Standard Error 0.121	-0.66 units on a scale Standard Error 0.118

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Duloxetine - Acute n=90 Participants Participants received 30 or 60 mg Duloxetine orally once daily (QD) for 13 weeks.	Placebo - Acute n=92 Participants Participants received Placebo orally once daily (QD) for 13 weeks.
Change From Baseline in Clinical Global Impression (CGI) Severity: Mental Illness Score	-0.16 units on a scale Standard Error 0.089	-0.15 units on a scale Standard Error 0.087

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Duloxetine - Acute n=87 Participants Participants received 30 or 60 mg Duloxetine orally once daily (QD) for 13 weeks.	Placebo - Acute n=88 Participants Participants received Placebo orally once daily (QD) for 13 weeks.
Change From Baseline in Functional Disability Inventory Child Form (FDI-Child)	-3.97 units on a scale Standard Error 1.038	-5.00 units on a scale Standard Error 1.021

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Duloxetine - Acute n=86 Participants Participants received 30 or 60 mg Duloxetine orally once daily (QD) for 13 weeks.	Placebo - Acute n=87 Participants Participants received Placebo orally once daily (QD) for 13 weeks.
Change From Baseline in Functional Disability Inventory Parent Form (FDI-Parent)	-3.25 units on a scale Standard Error 1.152	-4.17 units on a scale Standard Error 1.139

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Duloxetine - Acute n=89 Participants Participants received 30 or 60 mg Duloxetine orally once daily (QD) for 13 weeks.	Placebo - Acute n=89 Participants Participants received Placebo orally once daily (QD) for 13 weeks.
Change From Baseline in Children's Depression Inventory (CDI)	-3.28 units on a scale Standard Error 0.682	-2.45 units on a scale Standard Error 0.674

SECONDARY outcome

Timeframe: 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.

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.