A Long-term Study for the Treatment of Painful Diabetic Neuropathy

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00641719
• Collaborator: Shionogi (Industry)
• Enrollment: 258
• Locations: 25
• Arms: 2
• Duration (Months): 24
• Patients Per Site: 10.3
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of the study is to investigate safety and efficacy of duloxetine for patients with painful diabetic neuropathy at long-term use.

Condition or Disease	Intervention/Treatment	Phase
Diabetic Neuropathies	Drug: Duloxetine hydrochloride; Drug: Duloxetine hydrochloride	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 258 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Superiority Study of LY248686 Versus Placebo in the Treatment of Patients With Diabetic Peripheral Neuropathic Pain - Extension Phase
• Study Start Date: Mar 1, 2008
• Actual Primary Completion Date: Mar 1, 2010
• Actual Study Completion Date: Mar 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Duloxetine 40 mg Duloxetine 40 milligrams (mg) once daily (QD), orally (PO), 1 year	Drug: Duloxetine hydrochloride; Duloxetine 40 mg QD, PO, 1 year; Other Names: LY248686 Cymbalta
Experimental: Duloxetine 60 mg Duloxetine 60 mg QD, PO, 1 year	Drug: Duloxetine hydrochloride; Duloxetine 60 mg QD, PO, 1 year; Other Names: LY248686 Cymbalta

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Experienced an Adverse Event (AE) [baseline through 1 year]

   See the Reported Adverse Events section for details.

Secondary Outcome Measures

1. Patient Global Impression of Improvement (PGI-I) Scale at One Year Endpoint. [1 year]

   A scale that measures the participant's perception of improvement at the time of assessment compared with the start of treatment. The score ranges from 1 (very much better) to 7 (very much worse).

2. Change From Baseline to One Year Endpoint for Patient Global Impression of Improvement (PGI-I) Scale [baseline, 1 year]

   A scale that measures the participant's perception of improvement at the time of assessment compared with the start of treatment. The score ranges from 1 (very much better) to 7 (very much worse).

3. Brief Pain Inventory (BPI) Severity Scores at One Year Endpoint [1 year]

   A self-reported scale that measures the severity of pain. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). There are 4 questions assessing worst pain, least pain, and average pain in the past 24 hours, and the pain right now.

4. Change From Baseline to One Year Endpoint in Brief Pain Inventory (BPI) Severity Scores [baseline, 1 year]

   A self-reported scale that measures the severity of pain. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). There are 4 questions assessing worst pain, least pain, and average pain in the past 24 hours, and the pain right now.

5. Brief Pain Inventory (BPI) Interference Scores at One Year Endpoint [1 year]

   Self-reported scale measures interference of pain on function in past 24 hours for general activity, mood, walking ability, normal work, relations with other people, sleep, enjoyment of life. Scores range from 0 (does not interfere) to 10 (completely interferes). Average interference = self-reported scale measures interference of pain on average of 7 questions assessing interference of pain for general activity, mood, walking ability, normal work, relations with other people, sleep, enjoyment of life. Average interference scores range from 0 (does not interfere) to 10 (completely interferes).

6. Change From Baseline to One Year Endpoint in Brief Pain Inventory (BPI) Interference Scores [baseline, 1 year]

   Self-reported scale measures interference of pain on function in past 24 hours for general activity, mood, walking ability, normal work, relations with other people, sleep, enjoyment of life. Scores range from 0 (does not interfere) to 10 (completely interferes). Average interference = self-reported scale measures interference of pain on average of 7 questions assessing interference of pain for general activity, mood, walking ability, normal work, relations with other people, sleep, enjoyment of life. Average interference scores range from 0 (does not interfere) to 10 (completely interferes).

7. Beck Depression Inventory-II (BDI-II) Total Score at One Year Endpoint [1 year]

   A 21-item, participant-completed questionnaire to assess characteristics of depression. Each of the 21 items corresponding to a symptom of depression is summed to give a single score. There is a 4-point scale for each item ranging from 0 to 3. Total score of 0-13 is considered minimal range, 14-19 is mild, 20-28 is moderate, and 29-63 is severe.

8. Change From Baseline to One Year Endpoint in Beck Depression Inventory-II (BDI-II) Total Score [baseline, 1 year]

   A 21-item, participant-completed questionnaire to assess characteristics of depression. Each of the 21 items corresponding to a symptom of depression is summed to give a single score. There is a 4-point scale for each item ranging from 0 to 3. Total score of 0-13 is considered minimal range, 14-19 is mild, 20-28 is moderate, and 29-63 is severe.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Outpatients who have completed the 13-week treatment in the preceding study (Protocol No. 0715N0831: NCT00552175).

• Patients who desire to receive continued treatment with LY248686 from the preceding study.

• Patients with latest glycosylated hemoglobin (HbA1c) ≤9.0% before Visit 7.

• Patients who can provide written consent in person.

Exclusion Criteria:

• Patients who concurrently have serious cardiovascular, hepatic, renal, respiratory, or blood disease, or symptomatic peripheral vascular disease, and thus are considered inappropriate to be included in the study.

• Pregnant patients or women who desire to become pregnant during the study period, and breast feeding patients.

• Other patients judged by the investigator/subinvestigator to be inappropriate as a subject in this study.

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.	Aichi		Japan
2	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.	Aomori		Japan
3	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.	Chiba		Japan
4	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.	Fukui		Japan
5	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.	Fukuoka		Japan
6	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.	Fukushima		Japan
7	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.	Gunma		Japan
8	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.	Hiroshima		Japan
9	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.	Hokkaido		Japan
10	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.	Hyogo		Japan
11	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.	Ibaragi		Japan
12	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.	Kagoshima		Japan
13	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.	Kanagawa		Japan
14	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.	Kyoto		Japan
15	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.	Miyagi		Japan
16	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.	Niigata		Japan
17	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.	Oita		Japan
18	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.	Okayama		Japan
19	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.	Osaka		Japan
20	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
21	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.	Sizuoka		Japan
22	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.	Tochigi		Japan
23	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.	Tokushima		Japan
24	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.	Tokyo		Japan
25	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.	Toyama		Japan

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 - 5PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Lilly Clinical Trial Registry

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00641719
• Other Study ID Numbers: 12194; F1J-JE-HMFY
• First Posted: Mar 24, 2008
• Last Update Posted: Mar 31, 2011
• Last Verified: Mar 1, 2011

• Additional relevant MeSH terms: Diabetic Neuropathies; Duloxetine Hydrochloride

Study Results

Participant Flow

Recruitment Details	This study, F1J-JE-HMFY (Study HMFY), is an open-label, long-term extension study of double-blind placebo-controlled study F1J-JE-HMFX (Study HMFX) (NCT00552175).
Pre-assignment Detail	Prior to start of extension study (HMFY), all participants in Study HMFX were re-randomized to duloxetine 40 or 60 mg regardless of the treatment they received in Study HMFX. Baseline values for the extension study HMFY represent those of 40- and 60-mg groups after re-randomization of participants.

Arm/Group Title	Duloxetine 40 mg	Duloxetine 60 mg
Arm/Group Description	Duloxetine 40 mg once daily (QD), orally (PO), 1 year	Duloxetine 60 mg QD, PO, 1 year
Period Title: Overall Study
STARTED	129	129
COMPLETED	99	92
NOT COMPLETED	30	37

Baseline Characteristics

Arm/Group Title	Duloxetine 40 mg	Duloxetine 60 mg	Total
Arm/Group Description	Duloxetine 40 mg once daily (QD), orally (PO), 1 year	Duloxetine 60 mg QD, PO, 1 year	Total of all reporting groups
Overall Participants	129	129	258
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.2 (10.5)	60.0 (9.6)	60.1 (10.0)
Sex: Female, Male (Count of Participants)
Female	40 31%	22 17.1%	62 24%
Male	89 69%	107 82.9%	196 76%
Race/Ethnicity, Customized (participants) [Number]
Number [participants]	129 100%	129 100%	258 100%
Region of Enrollment (participants) [Number]
Japan	129 100%	129 100%	258 100%
Duration of Diabetes (participants) [Number]
Less Than 5 Years	23 17.8%	25 19.4%	48 18.6%
5 to 10 Years	27 20.9%	23 17.8%	50 19.4%
Greater Than or Equal to 10 Years	76 58.9%	79 61.2%	155 60.1%
Unknown	3 2.3%	2 1.6%	5 1.9%
Type of Diabetes (participants) [Number]
Type I	8 6.2%	4 3.1%	12 4.7%
Type II	121 93.8%	125 96.9%	246 95.3%
Height (centimeters (cm)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeters (cm)]	163.69 (9.04)	165.12 (7.75)	164.41 (8.44)
Weight (kilograms (kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms (kg)]	63.91 (12.13)	64.98 (11.57)	64.45 (11.84)
Body Mass Index (BMI) (kilograms/meters squared (kg/m^2)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms/meters squared (kg/m^2)]	23.79 (3.77)	23.77 (3.49)	23.78 (3.62)
Duration of Diabetic Neuropathy (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	3.91 (3.16)	4.29 (3.91)	4.10 (3.55)
Patient's Global Impressions of Improvement (PGI-I) Rate (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	3.0 (1.1)	3.1 (1.1)	3.1 (1.1)
Beck Depression Inventory - II (BDI-II) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	6.1 (6.4)	6.1 (6.4)	6.1 (6.4)
Brief Pain Inventory (BPI) Interference (units on a scale) [Mean (Standard Deviation) ]
General Activity	2.5 (2.4)	2.7 (2.2)	2.6 (2.3)
Mood	2.3 (2.3)	2.4 (2.2)	2.3 (2.2)
Walking Ability	2.2 (2.4)	2.3 (2.1)	2.3 (2.2)
Normal Work	2.3 (2.3)	2.3 (2.2)	2.3 (2.3)
Relation to People	1.6 (2.1)	1.9 (2.1)	1.8 (2.1)
Sleep	2.2 (2.3)	2.5 (2.4)	2.3 (2.4)
Enjoyment of Life	1.9 (2.1)	2.1 (2.1)	2.0 (2.1)
Average Interference Score	2.14 (2.09)	2.32 (2.06)	2.23 (2.07)
Brief Pain Inventory (BPI) - Pain Severity (units on a scale) [Mean (Standard Deviation) ]
Worst Pain	4.7 (2.0)	4.9 (2.0)	4.8 (2.0)
Least Pain	2.8 (2.0)	3.1 (2.1)	3.0 (2.0)
Average Pain	3.8 (1.9)	4.0 (1.9)	3.9 (1.9)
Pain Right Now	3.4 (2.1)	3.6 (2.1)	3.5 (2.1)

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Experienced an Adverse Event (AE)
Description	See the Reported Adverse Events section for details.
Time Frame	baseline through 1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Duloxetine 40 mg	Duloxetine 60 mg
Arm/Group Description	Duloxetine 40 mg once daily (QD), orally (PO), 1 year	Duloxetine 60 mg QD, PO, 1 year
Measure Participants	129	129
Serious Adverse Events	11 8.5%	22 17.1%
Adverse Events	126 97.7%	121 93.8%

2. Secondary Outcome

Title	Patient Global Impression of Improvement (PGI-I) Scale at One Year Endpoint.
Description	A scale that measures the participant's perception of improvement at the time of assessment compared with the start of treatment. The score ranges from 1 (very much better) to 7 (very much worse).
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT) population - participants were analyzed according to the groups to which they were originally assigned, whether or not they completed the protocol.

Arm/Group Title	Duloxetine 40 mg	Duloxetine 60 mg
Arm/Group Description	Duloxetine 40 mg once daily (QD), orally (PO), 1 year	Duloxetine 60 mg QD, PO, 1 year
Measure Participants	129	128
Mean (Standard Deviation) [units on a scale]	2.1 (0.9)	2.1 (1.0)

3. Secondary Outcome

Title	Change From Baseline to One Year Endpoint for Patient Global Impression of Improvement (PGI-I) Scale
Description	A scale that measures the participant's perception of improvement at the time of assessment compared with the start of treatment. The score ranges from 1 (very much better) to 7 (very much worse).
Time Frame	baseline, 1 year

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT) population - participants were analyzed according to the groups to which they were originally assigned, whether or not they completed the protocol.

Arm/Group Title	Duloxetine 40 mg	Duloxetine 60 mg
Arm/Group Description	Duloxetine 40 mg once daily (QD), orally (PO), 1 year	Duloxetine 60 mg QD, PO, 1 year
Measure Participants	129	128
Mean (Standard Deviation) [units on a scale]	-0.9 (1.1)	-1.0 (1.1)

4. Secondary Outcome

Title	Brief Pain Inventory (BPI) Severity Scores at One Year Endpoint
Description	A self-reported scale that measures the severity of pain. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). There are 4 questions assessing worst pain, least pain, and average pain in the past 24 hours, and the pain right now.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT) population - participants were analyzed according to the groups to which they were originally assigned, whether or not they completed the protocol.

Arm/Group Title	Duloxetine 40 mg	Duloxetine 60 mg
Arm/Group Description	Duloxetine 40 mg once daily (QD), orally (PO), 1 year	Duloxetine 60 mg QD, PO, 1 year
Measure Participants	129	128
Worst Pain	2.4 (1.9)	2.6 (2.0)
Least Pain	1.3 (1.5)	1.5 (1.5)
Average Pain	1.8 (1.5)	1.9 (1.6)
Pain Right Now	1.7 (1.6)	1.7 (1.6)

5. Secondary Outcome

Title	Change From Baseline to One Year Endpoint in Brief Pain Inventory (BPI) Severity Scores
Description	A self-reported scale that measures the severity of pain. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). There are 4 questions assessing worst pain, least pain, and average pain in the past 24 hours, and the pain right now.
Time Frame	baseline, 1 year

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT) population - participants were analyzed according to the groups to which they were originally assigned, whether or not they completed the protocol.

Arm/Group Title	Duloxetine 40 mg	Duloxetine 60 mg
Arm/Group Description	Duloxetine 40 mg once daily (QD), orally (PO), 1 year	Duloxetine 60 mg QD, PO, 1 year
Measure Participants	129	128
Worst Pain	-2.2 (1.8)	-2.3 (1.9)
Least Pain	-1.6 (1.6)	-1.6 (1.6)
Average Pain	-2.1 (1.7)	-2.1 (1.6)
Pain Right Now	-1.8 (1.7)	-1.8 (1.6)

6. Secondary Outcome

Title	Brief Pain Inventory (BPI) Interference Scores at One Year Endpoint
Description	Self-reported scale measures interference of pain on function in past 24 hours for general activity, mood, walking ability, normal work, relations with other people, sleep, enjoyment of life. Scores range from 0 (does not interfere) to 10 (completely interferes). Average interference = self-reported scale measures interference of pain on average of 7 questions assessing interference of pain for general activity, mood, walking ability, normal work, relations with other people, sleep, enjoyment of life. Average interference scores range from 0 (does not interfere) to 10 (completely interferes).
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT) population - participants were analyzed according to the groups to which they were originally assigned, whether or not they completed the protocol.

Arm/Group Title	Duloxetine 40 mg	Duloxetine 60 mg
Arm/Group Description	Duloxetine 40 mg once daily (QD), orally (PO), 1 year	Duloxetine 60 mg QD, PO, 1 year
Measure Participants	129	128
General Activities	1.4 (1.7)	1.4 (1.6)
Mood	1.2 (1.5)	1.3 (1.6)
Walking Ability	1.4 (1.7)	1.3 (1.5)
Normal Work	1.2 (1.7)	1.3 (1.5)
Relation to People	1.0 (1.5)	1.1 (1.4)
Sleep	1.2 (1.5)	1.3 (1.6)
Enjoyment of Life	1.2 (1.6)	1.3 (1.5)
Average Score	1.21 (1.52)	1.28 (1.48)

7. Secondary Outcome

Title	Change From Baseline to One Year Endpoint in Brief Pain Inventory (BPI) Interference Scores
Description	Self-reported scale measures interference of pain on function in past 24 hours for general activity, mood, walking ability, normal work, relations with other people, sleep, enjoyment of life. Scores range from 0 (does not interfere) to 10 (completely interferes). Average interference = self-reported scale measures interference of pain on average of 7 questions assessing interference of pain for general activity, mood, walking ability, normal work, relations with other people, sleep, enjoyment of life. Average interference scores range from 0 (does not interfere) to 10 (completely interferes).
Time Frame	baseline, 1 year

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT) population - participants were analyzed according to the groups to which they were originally assigned, whether or not they completed the protocol.

Arm/Group Title	Duloxetine 40 mg	Duloxetine 60 mg
Arm/Group Description	Duloxetine 40 mg once daily (QD), orally (PO), 1 year	Duloxetine 60 mg QD, PO, 1 year
Measure Participants	129	128
General Activities	-1.1 (1.8)	-1.3 (1.8)
Mood	-1.1 (1.8)	-1.0 (1.7)
Walking Ability	-0.8 (1.8)	-1.0 (1.6)
Normal Work	-1.0 (1.8)	-1.0 (1.6)
Relation to People	-0.6 (1.6)	-0.7 (1.6)
Sleep	-1.0 (2.1)	-1.1 (2.0)
Enjoyment of Life	-0.8 (1.7)	-0.8 (1.5)
Average Score	-0.93 (1.57)	-1.00 (1.48)

8. Secondary Outcome

Title	Beck Depression Inventory-II (BDI-II) Total Score at One Year Endpoint
Description	A 21-item, participant-completed questionnaire to assess characteristics of depression. Each of the 21 items corresponding to a symptom of depression is summed to give a single score. There is a 4-point scale for each item ranging from 0 to 3. Total score of 0-13 is considered minimal range, 14-19 is mild, 20-28 is moderate, and 29-63 is severe.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT) population - participants were analyzed according to the groups to which they were originally assigned, whether or not they completed the protocol.

Arm/Group Title	Duloxetine 40 mg	Duloxetine 60 mg
Arm/Group Description	Duloxetine 40 mg once daily (QD), orally (PO), 1 year	Duloxetine 60 mg QD, PO, 1 year
Measure Participants	129	128
Mean (Standard Deviation) [units on a scale]	6.3 (7.1)	5.4 (5.8)

9. Secondary Outcome

Title	Change From Baseline to One Year Endpoint in Beck Depression Inventory-II (BDI-II) Total Score
Description	A 21-item, participant-completed questionnaire to assess characteristics of depression. Each of the 21 items corresponding to a symptom of depression is summed to give a single score. There is a 4-point scale for each item ranging from 0 to 3. Total score of 0-13 is considered minimal range, 14-19 is mild, 20-28 is moderate, and 29-63 is severe.
Time Frame	baseline, 1 year

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT) population - participants were analyzed according to the groups to which they were originally assigned, whether or not they completed the protocol.

Arm/Group Title	Duloxetine 40 mg	Duloxetine 60 mg
Arm/Group Description	Duloxetine 40 mg once daily (QD), orally (PO), 1 year	Duloxetine 60 mg QD, PO, 1 year
Measure Participants	129	128
Mean (Standard Deviation) [units on a scale]	0.2 (4.4)	-0.7 (3.7)

Adverse Events

Arm/Group Title	Duloxetine 40 mg		Duloxetine 60 mg
Arm/Group Description	Duloxetine 40 mg once daily (QD), orally (PO), 1 year		Duloxetine 60 mg QD, PO, 1 year
All Cause Mortality
	Duloxetine 40 mg		Duloxetine 60 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Duloxetine 40 mg		Duloxetine 60 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/129 (8.5%)		22/129 (17.1%)
Cardiac disorders
Acute myocardial infarction	0/129 (0%)	0	2/129 (1.6%)	2
Angina pectoris	0/129 (0%)	0	1/129 (0.8%)	1
Cardiac failure	0/129 (0%)	0	1/129 (0.8%)	1
Cardiac failure congestive	0/129 (0%)	0	1/129 (0.8%)	1
Myocardial ischaemia	1/129 (0.8%)	1	0/129 (0%)	0
Eye disorders
Glaucoma	0/129 (0%)	0	1/129 (0.8%)	1
Gastrointestinal disorders
Colonic polyp	0/129 (0%)	0	1/129 (0.8%)	1
Ileus	0/129 (0%)	0	1/129 (0.8%)	1
General disorders
Generalised oedema	0/129 (0%)	0	1/129 (0.8%)	1
Infections and infestations
Bronchopneumonia	0/129 (0%)	0	1/129 (0.8%)	1
Diabetic gangrene	0/129 (0%)	0	1/129 (0.8%)	1
Infected epidermal cyst	0/129 (0%)	0	1/129 (0.8%)	1
Pyonephrosis	1/129 (0.8%)	1	0/129 (0%)	0
Injury, poisoning and procedural complications
Clavicle fracture	0/129 (0%)	0	1/129 (0.8%)	1
Femoral neck fracture	0/129 (0%)	0	1/129 (0.8%)	1
Foot fracture	1/129 (0.8%)	1	0/129 (0%)	0
Lung injury	0/129 (0%)	0	1/129 (0.8%)	1
Pelvic fracture	0/129 (0%)	0	1/129 (0.8%)	1
Rib fracture	0/129 (0%)	0	2/129 (1.6%)	2
Spinal compression fracture	0/129 (0%)	0	1/129 (0.8%)	1
Subdural haematoma	0/129 (0%)	0	1/129 (0.8%)	1
Thoracic vertebral fracture	0/129 (0%)	0	1/129 (0.8%)	1
Vertebral injury	0/129 (0%)	0	1/129 (0.8%)	1
Metabolism and nutrition disorders
Hypoglycaemia	0/129 (0%)	0	1/129 (0.8%)	1
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	1/129 (0.8%)	1	0/129 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer	1/129 (0.8%)	1	0/129 (0%)	0
Gastric cancer	0/129 (0%)	0	1/129 (0.8%)	1
Hepatic neoplasm malignant	0/129 (0%)	0	2/129 (1.6%)	2
Lymphoma	2/129 (1.6%)	3	0/129 (0%)	0
Metastases to liver	0/129 (0%)	0	1/129 (0.8%)	1
Metastases to lung	0/129 (0%)	0	1/129 (0.8%)	1
Pancreatic carcinoma	0/129 (0%)	0	1/129 (0.8%)	1
Tumour embolism	0/129 (0%)	0	1/129 (0.8%)	1
Tumour invasion	0/129 (0%)	0	1/129 (0.8%)	1
Nervous system disorders
Carotid artery stenosis	0/129 (0%)	0	1/129 (0.8%)	1
Cerebral infarction	1/129 (0.8%)	1	0/129 (0%)	0
Loss of consciousness	0/129 (0%)	0	1/129 (0.8%)	1
Reproductive system and breast disorders
Uterine prolapse	1/129 (0.8%)	1	0/129 (0%)	0
Respiratory, thoracic and mediastinal disorders
Nasal cyst	1/129 (0.8%)	1	0/129 (0%)	0
Pneumonia aspiration	1/129 (0.8%)	1	0/129 (0%)	0
Pneumothorax	0/129 (0%)	0	1/129 (0.8%)	1
Other (Not Including Serious) Adverse Events
	Duloxetine 40 mg		Duloxetine 60 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	126/129 (97.7%)		121/129 (93.8%)
Eye disorders
Diabetic retinopathy	8/129 (6.2%)	8	3/129 (2.3%)	3
Gastrointestinal disorders
Constipation	17/129 (13.2%)	19	17/129 (13.2%)	19
Diarrhoea	9/129 (7%)	10	7/129 (5.4%)	7
Nausea	14/129 (10.9%)	16	13/129 (10.1%)	15
Stomach discomfort	4/129 (3.1%)	7	7/129 (5.4%)	7
Vomiting	9/129 (7%)	11	10/129 (7.8%)	12
General disorders
Oedema peripheral	7/129 (5.4%)	9	8/129 (6.2%)	8
Thirst	5/129 (3.9%)	5	8/129 (6.2%)	9
Infections and infestations
Nasopharyngitis	36/129 (27.9%)	52	31/129 (24%)	39
Pharyngitis	5/129 (3.9%)	6	11/129 (8.5%)	12
Injury, poisoning and procedural complications
Contusion	10/129 (7.8%)	11	12/129 (9.3%)	20
Investigations
Alanine aminotransferase increased	12/129 (9.3%)	12	13/129 (10.1%)	15
Aspartate aminotransferase increased	13/129 (10.1%)	13	12/129 (9.3%)	14
Blood alkaline phosphatase increased	6/129 (4.7%)	6	7/129 (5.4%)	8
Blood creatine phosphokinase increased	12/129 (9.3%)	13	12/129 (9.3%)	12
Blood creatinine increased	3/129 (2.3%)	4	8/129 (6.2%)	9
Blood glucose decreased	14/129 (10.9%)	22	8/129 (6.2%)	9
Blood glucose increased	14/129 (10.9%)	21	12/129 (9.3%)	14
Blood lactate dehydrogenase increased	7/129 (5.4%)	7	5/129 (3.9%)	5
Blood potassium increased	7/129 (5.4%)	8	7/129 (5.4%)	10
Blood triglycerides increased	9/129 (7%)	11	10/129 (7.8%)	10
Blood urea increased	7/129 (5.4%)	7	4/129 (3.1%)	4
Blood uric acid increased	6/129 (4.7%)	7	8/129 (6.2%)	8
Blood urine present	4/129 (3.1%)	4	7/129 (5.4%)	8
Gamma-glutamyltransferase increased	10/129 (7.8%)	10	11/129 (8.5%)	11
Glycosylated haemoglobin increased	31/129 (24%)	32	29/129 (22.5%)	29
Urine albumin/creatinine ratio increased	10/129 (7.8%)	11	15/129 (11.6%)	15
Weight increased	12/129 (9.3%)	13	11/129 (8.5%)	11
White blood cell count increased	13/129 (10.1%)	16	8/129 (6.2%)	8
Metabolism and nutrition disorders
Diabetes mellitus	12/129 (9.3%)	13	11/129 (8.5%)	11
Hypoglycaemia	14/129 (10.9%)	34	11/129 (8.5%)	18
Musculoskeletal and connective tissue disorders
Back pain	5/129 (3.9%)	5	9/129 (7%)	10
Nervous system disorders
Dizziness	10/129 (7.8%)	12	8/129 (6.2%)	11
Headache	11/129 (8.5%)	31	9/129 (7%)	13
Somnolence	17/129 (13.2%)	17	18/129 (14%)	18
Psychiatric disorders
Insomnia	11/129 (8.5%)	11	5/129 (3.9%)	5
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract inflammation	9/129 (7%)	14	3/129 (2.3%)	6
Skin and subcutaneous tissue disorders
Eczema	8/129 (6.2%)	9	10/129 (7.8%)	14
Vascular disorders
Hypertension	9/129 (7%)	12	8/129 (6.2%)	8
Orthostatic hypotension	4/129 (3.1%)	4	8/129 (6.2%)	8

Limitations/Caveats

[Not Specified]

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.