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

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01914666
• Collaborator: Shionogi (Industry)
• Enrollment: 151
• Location: 1
• Arm: 1
• Duration (Months): 15
• Patients Per Site Per Month: 10.1

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Back Pain Lower Back Chronic	Drug: Duloxetine	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 151 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 3 Clinical Study of Duloxetine Hydrochloride in Patients With CLBP - Open Label Long Term Extension Study
• Study Start Date: Sep 1, 2013
• Actual Primary Completion Date: Dec 1, 2014
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Duloxetine Duloxetine 20 milligram (mg) for first week, 40 mg for second week and 60 mg for next 48 weeks administered orally once daily. Tapering week doses of 40 mg for first week and 20 mg for second week.	Drug: Duloxetine; Administered orally; Other Names: Cymbalta LY248686

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Drug Related Adverse Events (AEs) or Any Serious AE's [Week 53]

   A summary of serious AEs and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Event module.

Secondary Outcome Measures

1. Change From Baseline in Brief Pain Inventory (BPI) Pain Severity Item and Interference Item to Week 50 [Baseline, Week 50]

   A self-reported scale measuring severity of pain and interference on function. Severity scores: 0 (no pain) to 10 (severe pain) on each question assessing worst pain, least pain, and average pain in past 24 hours, and pain right now. Interference scores: 0 (does not interfere) to 10 (completely interferes) on each question assessing interference of pain in past 24 hours for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. Average interference = average of non-missing scores of individual interference items.

2. Patient Global Impression of Improvement (PGI-Improvement) to Week 50 [Week 50]

   PGI-I measures a participant's perception of improvement at the time of assessment compared with the start of treatment. Score ranges from 1 (very much better) to 7 (very much worse).

3. Change From Baseline in Clinical Global Impression of Severity (CGI-Severity) to Week 50 [Baseline, Week 50]

   CGI-S measures severity of illness at the time of assessment compared with start of treatment with scores ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill participants).

4. Change From Baseline in Roland Morris Disability Questionnaire (RMDQ-24) to Week 50 [Baseline, Week 50]

   RMDQ-24 is a participant completed questionnaire and measures the degree of disability due to back pain. The questionnaire consists of 24 statements and the participant was instructed to put a mark next to each appropriate statement. The number of statements marked was summed by the clinician for a total score. The total score ranged from 0 (no disability) to 24 (severe disability).

5. Change From Baseline in 36-Item Short-Form Health Survey (SF-36) to Week 50 [Baseline, Week 50]

   SF-36 Health Status Survey is a generic, health-related scale assessing participant's quality of life on 8 domains: physical functioning, social functioning, bodily pain, vitality, mental health, role-physical, role-emotional and general health. Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale, with higher scores indicating better health status or functioning.

6. Change From Baseline in European Quality of Life Questionnaire-5 Dimension (EQ-5D) to Week 50 [Baseline, Week 50]

   The EQ-5D is a generic, multidimensional, health-related, quality-of-life instrument. The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood using a three level scale (no problem, some problems, and major problems). These combinations of attributes were converted into a weighted health-state Index Score according to the Japan population-based algorithm ranging from -0.111 to 1.0, with higher scores indicating better quality of life.

7. Change From Baseline in Beck Depression Inventory-II (BDI-II) to Week 50 [Baseline, Week 50]

   BDI-II is a 21-item, participant-completed questionnaire to assess characteristics of depression. Each of the 21 items corresponding to symptoms of depression were scored on a 4-point scale ranging from 0 to 3 and was summed to give a single score. A total score of 0-13 was considered minimal range, 14-19 was mild, 20-28 was moderate, and 29-63 was severe.

8. Change From Baseline in Columbia Suicide Severity Rating Scale (C-SSRS) to Week 52 [Baseline, Week 53]

   C-SSRS captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal behavior is defined as a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation is defined as a "yes" answer to any one of 5 suicidal ideation questions: wish to be dead, and 4 different categories of active suicidal ideation.

9. Number of Participants With Fall Events From Fall Questionnaire [Week 53]

   Participants evaluated their experience with and details of falls which were recorded. Percentage = (number of participants with fall events) /(total in treatment group) * 100.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 79 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

(Consecutive Participants):

• Participants who have completed the 15-week administration in the phase 3 clinical study of Duloxetine hydrochloride in participants with CLBP, study HMGY (NCT01855919)

• Female participants having child-bearing potential must test negative (-) on a pregnancy test

(New Participants):

• Participants with CLBP present for the preceding 6 months or longer

• Participants used nonsteroidal anti-inflammatory drugs for CLBP for less than 14 days on average per month in the past 3 months and less than 14 days in one month prior to study

• Participants having a score of ≥4 on Brief Pain Inventory (BPI) average pain score at participation of study

• Female participants having child-bearing potential must test negative (-) on a pregnancy test

Exclusion Criteria:

(Consecutive Participants):

• Participants having serious or unstable cardiovascular, hepatic, renal, metabolic, respiratory, or hematologic illness, symptomatic peripheral vascular disease, or other medical condition or psychiatric conditions that, in the opinion of investigator, would compromise participation or be likely to lead to hospitalization during the course of the study

• Participants having alanine aminotransferase or aspartate aminotransferase higher than 100 International Units per Liter (IU/L) or total bilirubin higher than 1.6 milligram per deciliter (mg/dL)

• Participants having serum creatinine level higher than 2.0 mg/dL, or had renal transplantation or receiving renal dialysis

• Participants having diagnosis seronegative spondyloarthropathy or rheumatoid arthritis

• Participants having primary painful condition due to other than CLBP

• Participants having uncorrected thyroid disease, uncontrolled narrow-angle glaucoma, history of uncontrolled seizures, or uncontrolled or poorly controlled hypertension

• Participants treating with a monoamine oxidase inhibitor (MAOI) within 14 days or the potential need to use an MAOI during the study or within 5 days of discontinuation of study drug

• Participants answering "yes" to any of the questions about active suicidal ideation/intent/behaviors occurring within the past month (Columbia Suicide Severity Rating Scale, Suicide Ideation section - Questions 4 and 5; Suicidal Behavior section)

• Pregnant participants or participants who are breast-feeding, or wished to be pregnant during the clinical trial period

• Participants cannot use appropriate contraceptive method or do not want to use that from participation of study until one month after the end of administration of the investigational drug

• Participants being considered as inappropriate for participation to the study for any medical or other reason as judged by the investigator

(New Participants):

• Participants having serious or unstable cardiovascular, hepatic, renal, metabolic, respiratory, or hematologic illness, symptomatic peripheral vascular disease, or other medical condition or psychiatric conditions that, in the opinion of investigator, would compromise participation or be likely to lead to hospitalization during the course of the study

• Participants having alanine aminotransferase or aspartate aminotransferase higher than 100 IU/L or total bilirubin higher than 1.6 mg/dL

• Participants having serum creatinine level higher than 2.0 mg/dL, or had renal transplantation or receiving renal dialysis

• Participants having diagnosis seronegative spondyloarthropathy or rheumatoid arthritis

• Participants having primary painful condition due to other than CLBP

• Participants having a history of low back surgery

• Participants having any previous diagnosis of psychosis, bipolar disorder, or schizoaffective disorder

• Participants having major depressive disorder as determined using depression module of the Mini-International Neuropsychiatric Interview

• Participants having uncorrected thyroid disease, uncontrolled narrow-angle glaucoma, history of uncontrolled seizures, or uncontrolled or poorly controlled hypertension

• Participants treating with a MAOI within 14 days or the potential need to use an MAOI during the study or within 5 days of discontinuation of study drug

• Participants answering "yes" to any of the questions about active suicidal ideation/intent/behaviors occurring within the past month (Columbia Suicide Severity Rating Scale, Suicide Ideation section - Questions 4 and 5; Suicidal Behavior section)

• Participants have known hypersensitivity to multiple medications

• Participants are non-ambulatory or require the use of crutches or a walker

• Participants having a history of substance abuse or dependence within the past year, excluding nicotine and caffeine

• Participants having a positive urine drug screen for any substances of abuse

• Participants have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication

• Participants have had previous exposure to duloxetine or completed / withdrawn from any study investigating duloxetine

• Pregnant participants or participants who are breast-feeding, or wished to be pregnant during the clinical trial period

• Participants cannot use appropriate contraceptive method or do not want to use that from participation of study until one month after the end of administration of the investigational drug

• Participants being considered as inappropriate for participation to the study for any medical or other reason as judged by the investigator

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Saitama		Japan	330-0063

Sponsors and Collaborators

• Eli Lilly and Company
• Shionogi

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559 ) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01914666
• Other Study ID Numbers: 14949; F1J-JE-HMHC
• First Posted: Aug 2, 2013
• Last Update Posted: Jan 27, 2016
• Last Verified: Dec 1, 2015

• Keywords provided by Eli Lilly and Company: Chronic Low Back Pain; CLBP
• Additional relevant MeSH terms: Back Pain; Duloxetine Hydrochloride

Study Results

Participant Flow

Arm/Group Title	Naïve	Rollover (Pre-Placebo)	Rollover (Pre-Duloxetine 60 mg)
Arm/Group Description	New participants (Pts) administered duloxetine 20 mg during Week 1, 40 mg during Week 2, and 60 mg for Weeks 3-50. Tapering doses of 40 mg for Week 51 and 20 mg for Week 52.	Consecutive participants (randomized to placebo in study F1J-JE-HMGY [NCT#01855919]) administered duloxetine 20 mg during Week 1, 40 mg during Week 2, and 60 mg for Weeks 3-50. Tapering doses of 40 mg for Week 51 and 20 mg for Week 52.	Consecutive participants (randomized to duloxetine in study F1J-JE-HMGY) administered duloxetine 20 mg during Week 1, 40 mg during Week 2, and 60 mg for Weeks 3-50. Tapering doses of 40 mg for Week 51 and 20 mg for Week 52.
Period Title: Treatment Period
STARTED	68	42	41
Received at Least 1 Dose of Study Drug	68	42	41
COMPLETED	55	36	33
NOT COMPLETED	13	6	8
Period Title: Treatment Period
STARTED	59	39	40
COMPLETED	59	39	40
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Naïve	Rollover (Pre-Placebo)	Rollover (Pre-Duloxetine 60 mg)	Total
Arm/Group Description	New participants administered duloxetine 20 milligrams (mg) during Week 1, 40 mg during Week 2, and 60 mg for Weeks 3-50. Tapering doses of 40 mg for Week 51 and 20 mg for Week 52.	Consecutive participants (randomized to placebo in study F1J-JE-HMGY) administered duloxetine 20 mg during Week 1, 40 mg during Week 2, and 60 mg for Weeks 3-50. Tapering doses of 40 mg for Week 51 and 20 mg for Week 52.	Consecutive participants (randomized to duloxetine in study F1J-JE-HMGY) administered duloxetine 20 mg during Week 1, 40 mg during Week 2, and 60 mg for Weeks 3-50. Tapering doses of 40 mg for Week 51 and 20 mg for Week 52.	Total of all reporting groups
Overall Participants	67	42	41	150
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.3 (13.9)	57.6 (12.0)	58.8 (11.1)	56.4 (12.8)
Sex: Female, Male (Count of Participants)
Female	36 53.7%	22 52.4%	22 53.7%	80 53.3%
Male	31 46.3%	20 47.6%	19 46.3%	70 46.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	67 100%	42 100%	41 100%	150 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Japan	67 100%	42 100%	41 100%	150 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

All the enrolled participants who received at least 1 dose of study drug.

Arm/Group Title	Naïve	Rollover (Pre-Placebo)	Rollover (Pre-Duloxetine 60 mg)
Arm/Group Description	New participants administered duloxetine 20 milligrams (mg) during Week 1, 40 mg during Week 2, and 60 mg for Weeks 3-50. Tapering doses of 40 mg for Week 51 and 20 mg for Week 52.	Consecutive participants (randomized to placebo in study F1J-JE-HMGY) administered duloxetine 20 mg during Week 1, 40 mg during Week 2, and 60 mg for Weeks 3-50. Tapering doses of 40 mg for Week 51 and 20 mg for Week 52.	Consecutive participants (randomized to duloxetine in study F1J-JE-HMGY) administered duloxetine 20 mg during Week 1, 40 mg during Week 2, and 60 mg for Weeks 3-50. Tapering doses of 40 mg for Week 51 and 20 mg for Week 52.
Measure Participants	68	42	41
Drug Related AEs	42 62.7%	16 38.1%	18 43.9%
Serious AEs	4 6%	3 7.1%	1 2.4%

2. Secondary Outcome

Title	Change From Baseline in Brief Pain Inventory (BPI) Pain Severity Item and Interference Item to Week 50
Description	A self-reported scale measuring severity of pain and interference on function. Severity scores: 0 (no pain) to 10 (severe pain) on each question assessing worst pain, least pain, and average pain in past 24 hours, and pain right now. Interference scores: 0 (does not interfere) to 10 (completely interferes) on each question assessing interference of pain in past 24 hours for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. Average interference = average of non-missing scores of individual interference items.
Time Frame	Baseline, Week 50

Outcome Measure Data

Analysis Population Description

(FAS): All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose BPI pain severity (average pain) scores. The last observation carried forward (LOCF) was used.

Arm/Group Title	Naïve	Rollover (Pre-Placebo)	Rollover (Pre-Duloxetine 60 mg)
Arm/Group Description	New participants administered duloxetine 20 milligrams (mg) during Week 1, 40 mg during Week 2, and 60 mg for Weeks 3-50. Tapering doses of 40 mg for Week 51 and 20 mg for Week 52.	Consecutive participants (randomized to placebo in study F1J-JE-HMGY) administered duloxetine 20 mg during Week 1, 40 mg during Week 2, and 60 mg for Weeks 3-50. Tapering doses of 40 mg for Week 51 and 20 mg for Week 52.	Consecutive participants (randomized to duloxetine in study F1J-JE-HMGY) administered duloxetine 20 mg during Week 1, 40 mg during Week 2, and 60 mg for Weeks 3-50. Tapering doses of 40 mg for Week 51 and 20 mg for Week 52.
Measure Participants	67	42	41
Average Pain	-3.30 (1.45)	-3.79 (1.66)	-2.88 (1.81)
Worst Pain	-4.16 (1.91)	-4.71 (2.21)	-3.24 (1.88)
Least Pain	-1.82 (1.54)	-2.52 (1.77)	-2.12 (1.71)
Pain Right Now	-2.70 (1.87)	-3.93 (1.74)	-2.68 (1.90)
General Activity	-3.22 (2.30)	-3.26 (2.51)	-2.24 (2.75)
Mood	-2.52 (2.55)	-3.12 (2.37)	-2.07 (2.49)
Walking Ability	-2.09 (2.16)	-2.74 (2.26)	-1.71 (3.11)
Normal Work	-3.22 (2.49)	-3.21 (2.23)	-2.05 (2.78)
Relationship with People	-1.42 (2.15)	-1.79 (2.37)	-0.83 (1.82)
Sleep	-1.73 (2.12)	-2.40 (2.56)	-1.34 (2.22)
Enjoyment of Life	-2.07 (2.27)	-2.50 (2.55)	-1.83 (2.40)
Average of 7 Interference Items	-2.33 (1.81)	-2.72 (2.05)	-1.72 (2.21)

3. Secondary Outcome

Title	Patient Global Impression of Improvement (PGI-Improvement) to Week 50
Description	PGI-I measures a participant's perception of improvement at the time of assessment compared with the start of treatment. Score ranges from 1 (very much better) to 7 (very much worse).
Time Frame	Week 50

Outcome Measure Data

Analysis Population Description

FAS: All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose BPI pain severity (average pain) scores. LOCF was used.

Arm/Group Title	Naïve	Rollover (Pre-Placebo)	Rollover (Pre-Duloxetine 60 mg)
Arm/Group Description	New participants administered duloxetine 20 milligrams (mg) during Week 1, 40 mg during Week 2, and 60 mg for Weeks 3-50. Tapering doses of 40 mg for Week 51 and 20 mg for Week 52.	Consecutive participants (randomized to placebo in study F1J-JE-HMGY) administered duloxetine 20 mg during Week 1, 40 mg during Week 2, and 60 mg for Weeks 3-50. Tapering doses of 40 mg for Week 51 and 20 mg for Week 52.	Consecutive participants (randomized to duloxetine in study F1J-JE-HMGY) administered duloxetine 20 mg during Week 1, 40 mg during Week 2, and 60 mg for Weeks 3-50. Tapering doses of 40 mg for Week 51 and 20 mg for Week 52.
Measure Participants	67	42	41
Mean (Standard Deviation) [units on a scale]	2.12 (0.88)	2.05 (0.82)	2.61 (1.16)

4. Secondary Outcome

Title	Change From Baseline in Clinical Global Impression of Severity (CGI-Severity) to Week 50
Description	CGI-S measures severity of illness at the time of assessment compared with start of treatment with scores ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill participants).
Time Frame	Baseline, Week 50

Outcome Measure Data

Analysis Population Description

FAS: All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose BPI pain severity (average pain) score. LOCF was used.

Arm/Group Title	Naïve	Rollover (Pre-Placebo)	Rollover (Pre-Duloxetine 60 mg)
Arm/Group Description	New participants administered duloxetine 20 milligrams (mg) during Week 1, 40 mg during Week 2, and 60 mg for Weeks 3-50. Tapering doses of 40 mg for Week 51 and 20 mg for Week 52.	Consecutive participants (randomized to placebo in study F1J-JE-HMGY) administered duloxetine 20 mg during Week 1, 40 mg during Week 2, and 60 mg for Weeks 3-50. Tapering doses of 40 mg for Week 51 and 20 mg for Week 52.	Consecutive participants (randomized to duloxetine in study F1J-JE-HMGY) administered duloxetine 20 mg during Week 1, 40 mg during Week 2, and 60 mg for Weeks 3-50. Tapering doses of 40 mg for Week 51 and 20 mg for Week 52.
Measure Participants	67	42	41
Mean (Standard Deviation) [units on a scale]	2.09 (0.81)	2.00 (0.73)	2.73 (0.98)

5. Secondary Outcome

Title	Change From Baseline in Roland Morris Disability Questionnaire (RMDQ-24) to Week 50
Description	RMDQ-24 is a participant completed questionnaire and measures the degree of disability due to back pain. The questionnaire consists of 24 statements and the participant was instructed to put a mark next to each appropriate statement. The number of statements marked was summed by the clinician for a total score. The total score ranged from 0 (no disability) to 24 (severe disability).
Time Frame	Baseline, Week 50

Outcome Measure Data

Analysis Population Description

FAS: All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose BPI pain severity (average pain) score. LOCF was used.

Arm/Group Title	Naïve	Rollover (Pre-Placebo)	Rollover (Pre-Duloxetine 60 mg)
Arm/Group Description	New participants administered duloxetine 20 milligrams (mg) during Week 1, 40 mg during Week 2, and 60 mg for Weeks 3-50. Tapering doses of 40 mg for Week 51 and 20 mg for Week 52.	Consecutive participants (randomized to placebo in study F1J-JE-HMGY) administered duloxetine 20 mg during Week 1, 40 mg during Week 2, and 60 mg for Weeks 3-50. Tapering doses of 40 mg for Week 51 and 20 mg for Week 52.	Consecutive participants (randomized to duloxetine in study F1J-JE-HMGY) administered duloxetine 20 mg during Week 1, 40 mg during Week 2, and 60 mg for Weeks 3-50. Tapering doses of 40 mg for Week 51 and 20 mg for Week 52.
Measure Participants	67	42	41
Mean (Standard Deviation) [units on a scale]	-3.69 (3.76)	-5.50 (5.64)	-3.29 (4.56)

6. Secondary Outcome

Title	Change From Baseline in 36-Item Short-Form Health Survey (SF-36) to Week 50
Description	SF-36 Health Status Survey is a generic, health-related scale assessing participant's quality of life on 8 domains: physical functioning, social functioning, bodily pain, vitality, mental health, role-physical, role-emotional and general health. Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale, with higher scores indicating better health status or functioning.
Time Frame	Baseline, Week 50

Outcome Measure Data

Analysis Population Description

FAS: All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose BPI pain severity (average pain) score. LOCF was used.

Arm/Group Title	Naïve	Rollover (Pre-Placebo)	Rollover (Pre-Duloxetine 60 mg)
Arm/Group Description	New participants administered duloxetine 20 milligrams (mg) during Week 1, 40 mg during Week 2, and 60 mg for Weeks 3-50. Tapering doses of 40 mg for Week 51 and 20 mg for Week 52.	Consecutive participants (randomized to placebo in study F1J-JE-HMGY) administered duloxetine 20 mg during Week 1, 40 mg during Week 2, and 60 mg for Weeks 3-50. Tapering doses of 40 mg for Week 51 and 20 mg for Week 52.	Consecutive participants (randomized to duloxetine in study F1J-JE-HMGY) administered duloxetine 20 mg during Week 1, 40 mg during Week 2, and 60 mg for Weeks 3-50. Tapering doses of 40 mg for Week 51 and 20 mg for Week 52.
Measure Participants	67	42	41
Physical Functioning	10.60 (15.21)	9.52 (21.91)	10.12 (17.66)
Role (Physical)	16.88 (20.73)	11.31 (24.24)	7.01 (21.66)
Bodily Pain	17.64 (16.32)	20.26 (22.09)	12.62 (16.58)
General Health	8.42 (13.81)	8.90 (14.54)	5.51 (18.57)
Vitality	10.07 (16.64)	13.24 (23.15)	6.10 (18.93)
Social Functioning	6.90 (21.24)	8.63 (19.22)	3.35 (20.16)
Role (Emotional)	11.57 (20.05)	11.51 (23.20)	4.47 (16.99)
Mental Health	5.97 (15.31)	8.81 (14.89)	4.63 (14.12)

7. Secondary Outcome

Title	Change From Baseline in European Quality of Life Questionnaire-5 Dimension (EQ-5D) to Week 50
Description	The EQ-5D is a generic, multidimensional, health-related, quality-of-life instrument. The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood using a three level scale (no problem, some problems, and major problems). These combinations of attributes were converted into a weighted health-state Index Score according to the Japan population-based algorithm ranging from -0.111 to 1.0, with higher scores indicating better quality of life.
Time Frame	Baseline, Week 50

Outcome Measure Data

Analysis Population Description

FAS: All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose BPI pain severity (average pain) scores. LOCF was used.

Arm/Group Title	Naïve	Rollover (Pre-Placebo)	Rollover (Pre-Duloxetine 60 mg)
Arm/Group Description	New participants administered duloxetine 20 milligrams (mg) during Week 1, 40 mg during Week 2, and 60 mg for Weeks 3-50. Tapering doses of 40 mg for Week 51 and 20 mg for Week 52.	Consecutive participants (randomized to placebo in study F1J-JE-HMGY) administered duloxetine 20 mg during Week 1, 40 mg during Week 2, and 60 mg for Weeks 3-50. Tapering doses of 40 mg for Week 51 and 20 mg for Week 52.	Consecutive participants (randomized to duloxetine in study F1J-JE-HMGY) administered duloxetine 20 mg during Week 1, 40 mg during Week 2, and 60 mg for Weeks 3-50. Tapering doses of 40 mg for Week 51 and 20 mg for Week 52.
Measure Participants	67	42	41
Mean (Standard Deviation) [units on a scale]	0.16 (0.16)	0.15 (0.15)	0.11 (0.15)

8. Secondary Outcome

Title	Change From Baseline in Beck Depression Inventory-II (BDI-II) to Week 50
Description	BDI-II is a 21-item, participant-completed questionnaire to assess characteristics of depression. Each of the 21 items corresponding to symptoms of depression were scored on a 4-point scale ranging from 0 to 3 and was summed to give a single score. A total score of 0-13 was considered minimal range, 14-19 was mild, 20-28 was moderate, and 29-63 was severe.
Time Frame	Baseline, Week 50

Outcome Measure Data

Analysis Population Description

FAS: All randomized participants who received at least 1 dose of study drug and had baseline and at least 1 post-dose BPI pain severity (average pain) scores. LOCF was used.

Arm/Group Title	Naïve	Rollover (Pre-Placebo)	Rollover (Pre-Duloxetine 60 mg)
Arm/Group Description	New participants administered duloxetine 20 milligrams (mg) during Week 1, 40 mg during Week 2, and 60 mg for Weeks 3-50. Tapering doses of 40 mg for Week 51 and 20 mg for Week 52.	Consecutive participants (randomized to placebo in study F1J-JE-HMGY) administered duloxetine 20 mg during Week 1, 40 mg during Week 2, and 60 mg for Weeks 3-50. Tapering doses of 40 mg for Week 51 and 20 mg for Week 52.	Consecutive participants (randomized to duloxetine in study F1J-JE-HMGY) administered duloxetine 20 mg during Week 1, 40 mg during Week 2, and 60 mg for Weeks 3-50. Tapering doses of 40 mg for Week 51 and 20 mg for Week 52.
Measure Participants	67	42	41
Mean (Standard Deviation) [units on a scale]	-1.81 (5.32)	-1.83 (5.00)	-0.56 (3.75)

9. Secondary Outcome

Title	Change From Baseline in Columbia Suicide Severity Rating Scale (C-SSRS) to Week 52
Description	C-SSRS captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal behavior is defined as a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation is defined as a "yes" answer to any one of 5 suicidal ideation questions: wish to be dead, and 4 different categories of active suicidal ideation.
Time Frame	Baseline, Week 53

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug, responded no at baseline to the suicide related questionnaire and had data at post-treatment for each question.LOCF was used.

Arm/Group Title	Naïve	Rollover (Pre-Placebo)	Rollover (Pre-Duloxetine 60 mg)
Arm/Group Description	New participants administered duloxetine 20 milligrams (mg) during Week 1, 40 mg during Week 2, and 60 mg for Weeks 3-50. Tapering doses of 40 mg for Week 51 and 20 mg for Week 52.	Consecutive participants (randomized to placebo in study F1J-JE-HMGY) administered duloxetine 20 mg during Week 1, 40 mg during Week 2, and 60 mg for Weeks 3-50. Tapering doses of 40 mg for Week 51 and 20 mg for Week 52.	Consecutive participants (randomized to duloxetine in study F1J-JE-HMGY) administered duloxetine 20 mg during Week 1, 40 mg during Week 2, and 60 mg for Weeks 3-50. Tapering doses of 40 mg for Week 51 and 20 mg for Week 52.
Measure Participants	65	39	40
Suicidal Ideation- wish to be dead (n=65,39,40)	0 0%	0 0%	0 0%
Nonspecific suicidal thoughts (n=67,42,41)	0 0%	0 0%	0 0%
Suicidal Behavior (n=67,42,41)	0 0%	0 0%	0 0%

10. Secondary Outcome

Title	Number of Participants With Fall Events From Fall Questionnaire
Description	Participants evaluated their experience with and details of falls which were recorded. Percentage = (number of participants with fall events) /(total in treatment group) * 100.
Time Frame	Week 53

Outcome Measure Data

Analysis Population Description

All the enrolled participants who received at least 1 dose of study drug.

Arm/Group Title	Naïve	Rollover (Pre-Placebo)	Rollover (Pre-Duloxetine 60 mg)
Arm/Group Description	New participants administered duloxetine 20 milligrams (mg) during Week 1, 40 mg during Week 2, and 60 mg for Weeks 3-50. Tapering doses of 40 mg for Week 51 and 20 mg for Week 52.	Consecutive participants (randomized to placebo in study F1J-JE-HMGY) administered duloxetine 20 mg during Week 1, 40 mg during Week 2, and 60 mg for Weeks 3-50. Tapering doses of 40 mg for Week 51 and 20 mg for Week 52.	Consecutive participants (randomized to duloxetine in study F1J-JE-HMGY) administered duloxetine 20 mg during Week 1, 40 mg during Week 2, and 60 mg for Weeks 3-50. Tapering doses of 40 mg for Week 51 and 20 mg for Week 52.
Measure Participants	68	42	41
Number [participants]	13 19.4%	5 11.9%	6 14.6%

Adverse Events

Adverse Event Reporting Description	AEs for all participants who received at least one dose of study drug.
Arm/Group Title	Naïve, Rollover (Pre-Placebo), Rollover (Pre-Duloxetine 60 mg)
Arm/Group Description	All participants from Naïve, Rollover (Pre-Placebo), Rollover (Pre-Duloxetine 60 mg) groups combined.
All Cause Mortality
	Naïve, Rollover (Pre-Placebo), Rollover (Pre-Duloxetine 60 mg)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Naïve, Rollover (Pre-Placebo), Rollover (Pre-Duloxetine 60 mg)
	Affected / at Risk (%)	# Events
Total	8/151 (5.3%)
Eye disorders
Angle closure glaucoma	1/151 (0.7%)	1
Gastrointestinal disorders
Large intestine perforation	1/151 (0.7%)	1
Large intestine polyp	1/151 (0.7%)	1
General disorders
Death	1/151 (0.7%)	1
Injury, poisoning and procedural complications
Forearm fracture	1/151 (0.7%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Oesophageal carcinoma	1/151 (0.7%)	1
Nervous system disorders
Brain stem infarction	1/151 (0.7%)	1
Respiratory, thoracic and mediastinal disorders
Pneumothorax	1/151 (0.7%)	1
Other (Not Including Serious) Adverse Events
	Naïve, Rollover (Pre-Placebo), Rollover (Pre-Duloxetine 60 mg)
	Affected / at Risk (%)	# Events
Total	129/151 (85.4%)
Blood and lymphatic system disorders
Anaemia	2/151 (1.3%)	2
Iron deficiency anaemia	1/151 (0.7%)	1
Cardiac disorders
Arrhythmia	1/151 (0.7%)	1
Palpitations	1/151 (0.7%)	1
Tachycardia	1/151 (0.7%)	1
Ventricular extrasystoles	3/151 (2%)	4
Ear and labyrinth disorders
Tinnitus	5/151 (3.3%)	5
Vertigo	4/151 (2.6%)	4
Eye disorders
Chalazion	1/151 (0.7%)	1
Conjunctivitis	1/151 (0.7%)	1
Dry eye	1/151 (0.7%)	1
Retinal haemorrhage	1/151 (0.7%)	1
Gastrointestinal disorders
Abdominal discomfort	7/151 (4.6%)	7
Abdominal distension	1/151 (0.7%)	1
Abdominal pain	1/151 (0.7%)	1
Abdominal pain upper	3/151 (2%)	3
Anal fissure	1/151 (0.7%)	1
Aphthous stomatitis	1/151 (0.7%)	1
Barrett's oesophagus	1/151 (0.7%)	1
Constipation	15/151 (9.9%)	15
Dental caries	8/151 (5.3%)	8
Diarrhoea	4/151 (2.6%)	4
Dyschezia	1/151 (0.7%)	1
Dyspepsia	2/151 (1.3%)	2
Dysphagia	1/151 (0.7%)	1
Enterocolitis	1/151 (0.7%)	1
Gastric polyps	1/151 (0.7%)	1
Gastritis	2/151 (1.3%)	2
Gastrooesophageal reflux disease	1/151 (0.7%)	1
Haematochezia	1/151 (0.7%)	1
Haemorrhoids	1/151 (0.7%)	1
Hiatus hernia	1/151 (0.7%)	1
Large intestine polyp	1/151 (0.7%)	1
Nausea	16/151 (10.6%)	18
Periodontal disease	1/151 (0.7%)	1
Stomatitis	1/151 (0.7%)	1
Toothache	1/151 (0.7%)	1
General disorders
Asthenia	1/151 (0.7%)	1
Chest discomfort	1/151 (0.7%)	1
Chest pain	1/151 (0.7%)	1
Feeling abnormal	2/151 (1.3%)	2
Malaise	4/151 (2.6%)	4
Oedema peripheral	1/151 (0.7%)	1
Thirst	9/151 (6%)	9
Hepatobiliary disorders
Hepatic mass	1/151 (0.7%)	1
Hepatic steatosis	2/151 (1.3%)	2
Immune system disorders
Sarcoidosis	1/151 (0.7%)	1
Seasonal allergy	1/151 (0.7%)	1
Infections and infestations
Acarodermatitis	2/151 (1.3%)	2
Acute tonsillitis	1/151 (0.7%)	1
Anal abscess	1/151 (0.7%)	1
Bronchitis	6/151 (4%)	7
Cystitis	2/151 (1.3%)	3
Erythema infectiosum	1/151 (0.7%)	1
Furuncle	1/151 (0.7%)	1
Gastroenteritis	5/151 (3.3%)	6
Gingival abscess	1/151 (0.7%)	1
Gingival infection	2/151 (1.3%)	2
Gingivitis	2/151 (1.3%)	3
Herpes zoster	1/151 (0.7%)	1
Infected dermal cyst	1/151 (0.7%)	1
Influenza	7/151 (4.6%)	7
Nasopharyngitis	37/151 (24.5%)	48
Oral herpes	1/151 (0.7%)	1
Paronychia	1/151 (0.7%)	1
Periodontitis	1/151 (0.7%)	1
Pharyngitis	5/151 (3.3%)	5
Pneumonia	2/151 (1.3%)	2
Subcutaneous abscess	1/151 (0.7%)	2
Tonsillitis	1/151 (0.7%)	1
Injury, poisoning and procedural complications
Animal bite	1/151 (0.7%)	1
Bone contusion	4/151 (2.6%)	4
Burns first degree	1/151 (0.7%)	1
Contusion	17/151 (11.3%)	26
Epicondylitis	5/151 (3.3%)	5
Excoriation	2/151 (1.3%)	2
Hand fracture	2/151 (1.3%)	2
Heat illness	2/151 (1.3%)	3
Laceration	1/151 (0.7%)	1
Ligament injury	1/151 (0.7%)	1
Ligament sprain	8/151 (5.3%)	12
Lower limb fracture	1/151 (0.7%)	1
Meniscus injury	1/151 (0.7%)	1
Muscle injury	1/151 (0.7%)	1
Muscle strain	1/151 (0.7%)	1
Procedural pain	1/151 (0.7%)	1
Radius fracture	1/151 (0.7%)	1
Rib fracture	2/151 (1.3%)	2
Spinal compression fracture	1/151 (0.7%)	1
Thermal burn	2/151 (1.3%)	2
Traumatic haematoma	1/151 (0.7%)	1
Wound	4/151 (2.6%)	4
Investigations
Blood creatine phosphokinase increased	2/151 (1.3%)	2
Blood creatinine increased	1/151 (0.7%)	1
Blood lactate dehydrogenase increased	1/151 (0.7%)	2
Blood triglycerides increased	1/151 (0.7%)	1
Gamma-glutamyltransferase increased	2/151 (1.3%)	2
Liver function test abnormal	4/151 (2.6%)	4
Occult blood	1/151 (0.7%)	1
Metabolism and nutrition disorders
Decreased appetite	3/151 (2%)	3
Dehydration	1/151 (0.7%)	1
Diabetes mellitus	2/151 (1.3%)	2
Gout	1/151 (0.7%)	1
Hyperlipidaemia	2/151 (1.3%)	2
Hyperuricaemia	1/151 (0.7%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	11/151 (7.3%)	13
Arthritis	1/151 (0.7%)	1
Back pain	5/151 (3.3%)	6
Cervical spinal stenosis	1/151 (0.7%)	1
Fasciitis	1/151 (0.7%)	1
Intervertebral disc degeneration	1/151 (0.7%)	1
Intervertebral disc disorder	3/151 (2%)	3
Lumbar spinal stenosis	1/151 (0.7%)	1
Muscle spasms	2/151 (1.3%)	2
Musculoskeletal pain	3/151 (2%)	3
Myalgia	2/151 (1.3%)	2
Neck pain	1/151 (0.7%)	1
Osteoarthritis	3/151 (2%)	3
Osteoporosis	2/151 (1.3%)	2
Pain in extremity	3/151 (2%)	4
Periarthritis	8/151 (5.3%)	10
Plantar fasciitis	1/151 (0.7%)	1
Rotator cuff syndrome	2/151 (1.3%)	2
Spinal osteoarthritis	3/151 (2%)	3
Synovial cyst	2/151 (1.3%)	2
Temporomandibular joint syndrome	1/151 (0.7%)	1
Tenosynovitis	1/151 (0.7%)	1
Tenosynovitis stenosans	1/151 (0.7%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign neoplasm of skin	1/151 (0.7%)	1
Morton's neuroma	1/151 (0.7%)	1
Skin papilloma	1/151 (0.7%)	1
Nervous system disorders
Autonomic nervous system imbalance	1/151 (0.7%)	1
Carpal tunnel syndrome	1/151 (0.7%)	1
Cervical radiculopathy	1/151 (0.7%)	1
Dizziness	8/151 (5.3%)	11
Dizziness postural	5/151 (3.3%)	5
Dysgeusia	1/151 (0.7%)	1
Headache	10/151 (6.6%)	11
Hypoaesthesia	2/151 (1.3%)	2
Intercostal neuralgia	1/151 (0.7%)	1
Myelopathy	1/151 (0.7%)	1
Radiculitis cervical	1/151 (0.7%)	1
Sensory disturbance	1/151 (0.7%)	1
Somnolence	29/151 (19.2%)	30
Syncope	1/151 (0.7%)	1
Tension headache	2/151 (1.3%)	2
Psychiatric disorders
Anxiety	1/151 (0.7%)	1
Insomnia	4/151 (2.6%)	4
Renal and urinary disorders
Dysuria	2/151 (1.3%)	2
Hypertonic bladder	3/151 (2%)	3
Pollakiuria	1/151 (0.7%)	1
Reproductive system and breast disorders
Dysmenorrhoea	1/81 (1.2%)	1
Gynaecomastia	1/70 (1.4%)	1
Metrorrhagia	1/81 (1.2%)	1
Respiratory, thoracic and mediastinal disorders
Asthma	1/151 (0.7%)	1
Bronchitis chronic	1/151 (0.7%)	1
Oropharyngeal pain	1/151 (0.7%)	1
Rhinitis allergic	1/151 (0.7%)	1
Upper respiratory tract inflammation	1/151 (0.7%)	4
Skin and subcutaneous tissue disorders
Asteatosis	1/151 (0.7%)	1
Dermatitis allergic	2/151 (1.3%)	2
Dermatitis contact	1/151 (0.7%)	1
Eczema	2/151 (1.3%)	2
Eczema asteatotic	2/151 (1.3%)	2
Erythema	1/151 (0.7%)	1
Hyperkeratosis	1/151 (0.7%)	1
Night sweats	1/151 (0.7%)	1
Pruritus	2/151 (1.3%)	2
Rash	2/151 (1.3%)	2
Skin tightness	1/151 (0.7%)	1
Urticaria	2/151 (1.3%)	2
Urticaria cholinergic	1/151 (0.7%)	1
Vascular disorders
Hot flush	1/151 (0.7%)	1
Hypertension	2/151 (1.3%)	2
Peripheral coldness	1/151 (0.7%)	1

Limitations/Caveats

FAS:all randomized pts who received at least 1 dose of study drug and had at least 1 post-dose BPI pain severity (average pain) score. 1 Naïve group pt received at least 1 dose of study drug but had no post-dose data and not included in FAS.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.