A Study for the Treatment of Diabetic Peripheral Neuropathic Pain

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00552175
• Collaborator: Shionogi (Industry)
• Enrollment: 339
• Locations: 25
• Arms: 3
• Duration (Months): 16
• Patients Per Site: 13.6
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

The purpose of the study is to determine if duloxetine can help patients with painful diabetic neuropathy.

Condition or Disease	Intervention/Treatment	Phase
Diabetic Neuropathies	Drug: Duloxetine hydrochloride - 40 mg; Drug: placebo; Drug: Duloxetine hydrochloride - 60 mg	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 339 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Superiority Study of LY248686 Versus Placebo in the Treatment of Patients With Diabetic Peripheral Neuropathic Pain
• Study Start Date: Nov 1, 2007
• Actual Primary Completion Date: Mar 1, 2009
• Actual Study Completion Date: Mar 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Duloxetine 60 duloxetine 60 milligram (mg) taken orally every day	Drug: Duloxetine hydrochloride - 60 mg; duloxetine 60 mg taken orally every day; Other Names: LY248686 Cymbalta
Experimental: Duloxetine 40 Duloxetine 40 mg taken orally every day	Drug: Duloxetine hydrochloride - 40 mg; duloxetine 40 mg taken orally every day; Other Names: LY248686 Cymbalta
Placebo Comparator: Placebo placebo comparator taken orally every day	Drug: placebo; placebo taken orally every day

Outcome Measures

Primary Outcome Measures

1. Change From Baseline at Week 12 in Average Pain Severity Rating Using Diaries for the Combined Duloxetine Arms (40 mg + 60 mg) [Baseline, 12 weeks]

   Average pain severity was measured using an 11-point numerical rating scale, collected by diaries and expressed as weekly mean. The scale is a self-reported instrument that measures the severity of pain based on the average pain over the past 24-hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine).

Secondary Outcome Measures

1. Change From Baseline at Week 12 in Average Pain Severity Rating Score Using Diaries [Baseline, 12 weeks]

   Average pain severity was measured using an 11-point numerical rating scale, collected by diaries and expressed as weekly mean. The scale is a self-reported instrument that measures the severity of pain based on the average pain over the past 24-hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine).

2. Change From Baseline at Week 12 in Worst Pain Severity Score and Night Pain Severity Score Using Diaries for the Combined Duloxetine Arms (40 mg + 60 mg) [Baseline, 12 weeks]

   Pain severity for worst pain and night pain as measured by an 11-point numerical rating scale, collected by diaries and expressed as weekly means. A self-reported scale that measures the severity of pain based on the worst pain and night pain experienced over the past 24-hours. The worst pain and night pain severity scores each range from 0 (no pain) to 10 (pain as severe as you can imagine).

3. Change From Baseline at Week 12 in Worst Pain Severity Score and Night Pain Severity Score Using Diaries [Baseline, Week 12]

   Pain severity for worst pain and night pain as measured by an 11-point numerical rating scale, collected by diaries and expressed as weekly means. A self-reported scale that measures the severity of pain based on the worst pain and night pain experienced over the past 24-hours. The worst pain and night pain severity scores each range from 0 (no pain) to 10 (pain as severe as you can imagine).

4. Patient Global Impression of Improvement Scale at Week 12 in Combined Duloxetine Arms (40 mg + 60 mg) [Week 12]

   A scale that measures the patient'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).

5. Patient Global Impression of Improvement Scale at Week 12 [Week 12]

   A scale that measures the patient'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).

6. Change From Baseline in Brief Pain Inventory Severity Scores at Week 12 for the Combined Duloxetine Arms (40 mg + 60 mg) [Baseline, Week 12]

   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. Each question has a total range of scores from 0 to 10.

7. Change From Baseline in Brief Pain Inventory Severity Scores at Week 12 [Baseline, Week 12]

   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. Each question has a total range of scores from 0 to 10.

8. Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 for the Combined Duloxetine Arms (40 mg + 60 mg) [Baseline, Week 12]

   The Interference scores range from 0 (does not interfere) to 10 (completely interferes). There are 7 questions assessing the interference of pain in the past 24 hours for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. Each question has a total range of scores from 0 to 10.

9. Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 [Baseline, Week 12]

   The Interference scores range from 0 (does not interfere) to 10 (completely interferes). There are 7 questions assessing the interference of pain in the past 24 hours for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. Each question has a total range of scores from 0 to 10.

10. Change From Baseline in Beck Depression Inventory-II (BDI-II) Total Score at Week 12 for the Combined Duloxetine Arms (40 mg + 60 mg) [Baseline, Week 12]

    A 21-item, patient-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 four-point scale for each item ranging from 0 to 3. Total score ranges from 0 (no depression) to 63 (severe depression).

11. Change From Baseline in Beck Depression Inventory-II (BDI-II) Total Score at Week 12 [Baseline, Week 12]

    A 21-item, patient-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 four-point scale for each item ranging from 0 to 3. Total score ranges from 0 (no depression) to 63 (severe depression).

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients with pain due to bilateral peripheral neuropathy induced by type 1 or 2 diabetes mellitus. The pain must have been present for at least 6 months and be evaluable in feet, legs, or hands.

• Participants with hemoglobin A1c (HbA1c) less than or equal to 9.0 percent at Visit 1.

• Participants in whom HbA1c had been measured 42-70 days before Visit 1 and subsequent HbA1c levels have been within +/- 1.0 percent of the level at Visit 1.

• Participants with a mean of the 24-hour average pain severity scores (round off to a whole number) of 4 or higher, as calculated from the patient diary for 7 days immediately before Visit 2

Exclusion Criteria:

• Participants who have undergone renal transplant or who are currently on renal dialysis.

• Participants who have a history requiring pharmacotherapy within the past year or current history of psychiatric disease, such as mania, bipolar disorder, depression, anxiety disorder, or eating disorder.

• Participants with hypertension with poor control of blood pressure (systolic blood pressure greater than or equal to 180 millimeters of mercury (mmHg) or diastolic blood pressure greater than or equal to 110 mmHg

• Participants with alanine transaminase (ALT) or aspartate transaminase (AST) greater than or equal to 100 Units per Liter (U/L) at Visit 1.

• Participants unable to discontinue prohibited concomitant drugs or concomitant therapies after Visit 1.

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, ETS), 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.	Ibaraki		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, ETS), 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.	Shizuoka		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-5 PM 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: NCT00552175
• Other Study ID Numbers: 12191; 0715N0831; F1J-JE-HMFX
• First Posted: Nov 1, 2007
• Last Update Posted: Apr 13, 2010
• Last Verified: Mar 1, 2010

• Additional relevant MeSH terms: Neuralgia; Diabetic Neuropathies; Duloxetine Hydrochloride

Study Results

Participant Flow

Pre-assignment Detail	Full Analysis Set Population consisted of all randomized patients who had at least one post-baseline measure of the primary efficacy variable.

Arm/Group Title	Placebo	Duloxetine 40 mg	Duloxetine 60 mg
Arm/Group Description	placebo comparator taken orally every day	Duloxetine 40 milligrams (mg) taken orally every day	Duloxetine 60 milligrams (mg) taken orally every day
Period Title: Overall Study
STARTED	167	86	86
Full Analysis Set Population	167	85	86
COMPLETED	150	73	72
NOT COMPLETED	17	13	14

Baseline Characteristics

Arm/Group Title	Placebo	Duloxetine 40 mg	Duloxetine 60 mg	Total
Arm/Group Description	placebo comparator taken orally every day	Duloxetine 40 milligrams (mg) taken orally every day	Duloxetine 60 milligrams (mg) taken orally every day	Total of all reporting groups
Overall Participants	167	85	86	338
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.8 (9.2)	62.1 (9.3)	59.7 (12.1)	60.8 (10)
Sex: Female, Male (Count of Participants)
Female	38 22.8%	20 23.5%	24 27.9%	82 24.3%
Male	129 77.2%	65 76.5%	62 72.1%	256 75.7%
Race/Ethnicity, Customized (participants) [Number]
Japanese	167 100%	85 100%	86 100%	338 100%
Region of Enrollment (participants) [Number]
Japan	167 100%	85 100%	86 100%	338 100%
Duration of Diabetes (participants) [Number]
<5 years	33 19.8%	20 23.5%	16 18.6%	69 20.4%
5 - 10 years	32 19.2%	18 21.2%	14 16.3%	64 18.9%
>= 10 years	97 58.1%	47 55.3%	56 65.1%	200 59.2%
Unknown	5 3%	0 0%	0 0%	5 1.5%
Type of Diabetes (participants) [Number]
Type I	8 4.8%	5 5.9%	4 4.7%	17 5%
Type II	159 95.2%	80 94.1%	82 95.3%	321 95%
Beck Depression Inventory-II (BDI-II) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	8.8 (6.8)	9.4 (8.8)	9.4 (7.2)	9.1 (7.4)
Body Mass Index (BMI) (kilograms/square meters (kg/m^2)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms/square meters (kg/m^2)]	23.90 (3.70)	23.27 (3.67)	24.20 (3.50)	23.82 (3.65)
Brief Pain Inventory (BPI) Interference Scores (units on a scale) [Mean (Standard Deviation) ]
General Activity	4.4 (2.4)	4.5 (2.7)	4.5 (2.4)	4.5 (2.5)
Mood	4.2 (2.4)	3.9 (2.5)	4.2 (2.5)	4.1 (2.5)
Walking Ability	4.0 (2.6)	4.4 (2.8)	4.3 (2.5)	4.2 (2.6)
Normal Work	3.7 (2.7)	3.9 (2.6)	4.3 (2.5)	3.9 (2.6)
Relation to People	2.6 (2.5)	2.7 (2.7)	2.9 (2.4)	2.7 (2.5)
Sleep	3.9 (2.7)	4.0 (2.8)	4.3 (2.7)	4.0 (2.7)
Enjoyment of Life	3.5 (2.5)	3.7 (2.7)	4.0 (2.5)	3.7 (2.6)
Average of Interference Scores	3.75 (2.15)	3.88 (2.25)	4.09 (2.13)	3.87 (2.17)
Brief Pain Inventory (BPI) Severity Scores (units on a scale) [Mean (Standard Deviation) ]
Worst Pain	6.7 (1.4)	6.5 (1.4)	6.6 (1.5)	6.6 (1.4)
Least Pain	4.1 (1.8)	4.0 (1.8)	4.2 (1.6)	4.1 (1.8)
Average Pain	5.6 (1.3)	5.6 (1.3)	5.7 (1.3)	5.6 (1.3)
Pain Right Now	5.1 (1.7)	5.2 (1.8)	5.3 (1.4)	5.2 (1.7)
Duration of Diabetic Neuropathy (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	4.21 (4.44)	4.58 (3.90)	4.16 (3.67)	4.29 (4.11)
Height (centimeters (cm)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeters (cm)]	164.13 (8.65)	163.63 (8.78)	164.02 (7.32)	163.98 (8.34)
Weekly Means of 24-Hour Average Pain, Worst Pain, and Night Pain Diary Scores (units on a scale) [Mean (Standard Deviation) ]
Average Pain Score	5.78 (1.17)	5.79 (1.23)	5.76 (1.17)	5.78 (1.18)
Worst Pain Score	6.66 (1.25)	6.54 (1.33)	6.61 (1.33)	6.62 (1.29)
Night Pain Score	5.5 (1.49)	5.55 (1.64)	5.69 (1.54)	5.56 (1.54)
Weight (kilograms (kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms (kg)]	64.52 (11.93)	62.72 (13.35)	65.08 (10.23)	64.21 (11.9)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline at Week 12 in Average Pain Severity Rating Using Diaries for the Combined Duloxetine Arms (40 mg + 60 mg)
Description	Average pain severity was measured using an 11-point numerical rating scale, collected by diaries and expressed as weekly mean. The scale is a self-reported instrument that measures the severity of pain based on the average pain over the past 24-hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine).
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

Patients in the Full Analysis Set Population who had a post-baseline measurement in the variable being presented.

Arm/Group Title	Placebo	Duloxetine 40 mg and 60 mg Combined
Arm/Group Description	placebo comparator taken orally every day	Duloxetine 40 milligrams (mg) taken orally every day, and Duloxetine 60 mg taken orally every day.
Measure Participants	167	171
Least Squares Mean (Standard Error) [units on a scale]	-1.61 (0.18)	-2.47 (0.18)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 40 mg and 60 mg Combined
	Comments	The primary objective and primary efficacy analysis for the study was the analysis between the combined duloxetine arms and placebo.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Covariates: Baseline value of average pain score, type of Diabetes, Duration of diabetic peripheral neuropathic pain (DPNP).
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.87
	Confidence Interval	(2-Sided) 95%; -1.17 to -0.56
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.15
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

2. Secondary Outcome

Title	Change From Baseline at Week 12 in Average Pain Severity Rating Score Using Diaries
Description	Average pain severity was measured using an 11-point numerical rating scale, collected by diaries and expressed as weekly mean. The scale is a self-reported instrument that measures the severity of pain based on the average pain over the past 24-hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine).
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

Patients in the Full Analysis Set Population who had a post-baseline measurement in the variable being presented.

Arm/Group Title	Placebo	Duloxetine 40 mg	Duloxetine 60 mg
Arm/Group Description	placebo comparator taken orally every day	Duloxetine 40 milligrams (mg) taken orally every day	Duloxetine 60 milligrams (mg) taken orally every day
Measure Participants	167	85	86
Least Squares Mean (Standard Error) [units on a scale]	-1.61 (0.19)	-2.41 (0.21)	-2.53 (0.21)

3. Secondary Outcome

Title	Change From Baseline at Week 12 in Worst Pain Severity Score and Night Pain Severity Score Using Diaries for the Combined Duloxetine Arms (40 mg + 60 mg)
Description	Pain severity for worst pain and night pain as measured by an 11-point numerical rating scale, collected by diaries and expressed as weekly means. A self-reported scale that measures the severity of pain based on the worst pain and night pain experienced over the past 24-hours. The worst pain and night pain severity scores each range from 0 (no pain) to 10 (pain as severe as you can imagine).
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

Patients in the Full Analysis Set Population who had a post-baseline measurement in the variable being presented.

Arm/Group Title	Placebo	Duloxetine 40 mg and 60 mg Combined
Arm/Group Description	placebo comparator taken orally every day	Duloxetine 40 milligrams (mg) taken orally every day, and Duloxetine 60 mg taken orally every day.
Measure Participants	167	171
Worst Pain	-1.55 (0.19)	-2.51 (0.19)
Night Pain	-1.56 (0.19)	-2.39 (0.19)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 40 mg and 60 mg Combined
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-value for Worst Pain.
	Method	Mixed Models Analysis
	Comments	Covariates: Baseline value of worst pain score, type of Diabetes, Duration of diabetic peripheral neuropathic pain (DPNP).
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.96
	Confidence Interval	(2-Sided) 95%; -1.27 to -0.64
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 40 mg and 60 mg Combined
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-value for Night Pain.
	Method	Mixed Models Analysis
	Comments	Covariates: Baseline value of night pain score, type of Diabetes, Duration of diabetic peripheral neuropathic pain (DPNP).
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.83
	Confidence Interval	(2-Sided) 95%; -1.15 to -0.51
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

4. Secondary Outcome

Title	Change From Baseline at Week 12 in Worst Pain Severity Score and Night Pain Severity Score Using Diaries
Description	Pain severity for worst pain and night pain as measured by an 11-point numerical rating scale, collected by diaries and expressed as weekly means. A self-reported scale that measures the severity of pain based on the worst pain and night pain experienced over the past 24-hours. The worst pain and night pain severity scores each range from 0 (no pain) to 10 (pain as severe as you can imagine).
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Patients in the Full Analysis Set Population who had a post-baseline measurement in the variable being presented.

Arm/Group Title	Placebo	Duloxetine 40 mg	Duloxetine 60 mg
Arm/Group Description	placebo comparator taken orally every day	Duloxetine 40 milligrams (mg) taken orally every day	Duloxetine 60 milligrams (mg) taken orally every day
Measure Participants	167	85	86
Worst Pain	-1.55 (0.19)	-2.42 (0.22)	-2.59 (0.22)
Night Pain	-1.56 (0.19)	-2.33 (0.22)	-2.45 (0.23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 40 mg and 60 mg Combined
	Comments	Worst Pain analysis
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.87
	Confidence Interval	(2-Sided) 95%; -1.26 to -0.49
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 60 mg
	Comments	Worst Pain analysis
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-1.05
	Confidence Interval	(2-Sided) 95%; -1.43 to -0.66
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 40 mg and 60 mg Combined
	Comments	Night Pain analysis
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.78
	Confidence Interval	(2-Sided) 95%; -1.17 to -0.39
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 60 mg
	Comments	Night Pain analysis
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.89
	Confidence Interval	(2-Sided) 95%; -1.28 to -0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

5. Secondary Outcome

Title	Patient Global Impression of Improvement Scale at Week 12 in Combined Duloxetine Arms (40 mg + 60 mg)
Description	A scale that measures the patient'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	Week 12

Outcome Measure Data

Analysis Population Description

Patients in the Full Analysis Set Population who had a post-baseline measurement in the variable being presented.

Arm/Group Title	Placebo	Duloxetine 40 mg and 60 mg Combined
Arm/Group Description	placebo comparator taken orally every day	Duloxetine 40 milligrams (mg) taken orally every day, and Duloxetine 60 mg taken orally every day.
Measure Participants	165	169
Least Squares Mean (Standard Error) [units on a scale]	3.18 (0.12)	2.53 (0.12)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 40 mg and 60 mg Combined
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Covariates: Baseline value of average pain score, type of Diabetes, Duration of diabetic peripheral neuropathic pain (DPNP).
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.65
	Confidence Interval	(2-Sided) 95%; -0.85 to -0.44
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

6. Secondary Outcome

Title	Patient Global Impression of Improvement Scale at Week 12
Description	A scale that measures the patient'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	Week 12

Outcome Measure Data

Analysis Population Description

Patients in the Full Analysis Set Population who had a post-baseline measurement in the variable being presented.

Arm/Group Title	Placebo	Duloxetine 40 mg	Duloxetine 60 mg
Arm/Group Description	placebo comparator taken orally every day	Duloxetine 40 milligrams (mg) taken orally every day	Duloxetine 60 milligrams (mg) taken orally every day
Measure Participants	165	84	85
Least Squares Mean (Standard Error) [units on a scale]	3.18 (0.12)	2.53 (0.14)	2.52 (0.14)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 40 mg and 60 mg Combined
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.65
	Confidence Interval	(2-Sided) 95%; -0.9 to -0.39
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 60 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.65
	Confidence Interval	(2-Sided) 95%; -0.91 to -0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

7. Secondary Outcome

Title	Change From Baseline in Brief Pain Inventory Severity Scores at Week 12 for the Combined Duloxetine Arms (40 mg + 60 mg)
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. Each question has a total range of scores from 0 to 10.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Patients in the Full Analysis Set Population who had a post-baseline measurement in the variable being presented.

Arm/Group Title	Placebo	Duloxetine 40 mg and 60 mg Combined
Arm/Group Description	placebo comparator taken orally every day	Duloxetine 40 milligrams (mg) taken orally every day, and Duloxetine 60 mg taken orally every day.
Measure Participants	165	169
Worst Pain	-1.62 (0.21)	-2.59 (0.21)
Least Pain	-1.13 (0.21)	-1.98 (0.21)
Average Pain	-1.54 (0.2)	-2.54 (0.2)
Pain Right Now	-1.67 (0.22)	-2.59 (0.22)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 40 mg and 60 mg Combined
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-value for Worst Pain.
	Method	Mixed Models Analysis
	Comments	Covariates: Baseline value of worst pain score, type of Diabetes, Duration of diabetic peripheral neuropathic pain (DPNP).
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.98
	Confidence Interval	(2-Sided) 95%; -1.34 to -0.61
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 40 mg and 60 mg Combined
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-value for Least Pain.
	Method	Mixed Models Analysis
	Comments	Covariates: Baseline value of least pain score, type of Diabetes, Duration of diabetic peripheral neuropathic pain (DPNP).
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.85
	Confidence Interval	(2-Sided) 95%; -1.21 to -0.48
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 40 mg and 60 mg Combined
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-value for Average Pain.
	Method	Mixed Models Analysis
	Comments	Covariates: Baseline value of average pain score, type of Diabetes, Duration of diabetic peripheral neuropathic pain (DPNP).
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-1
	Confidence Interval	(2-Sided) 95%; -1.33 to -0.67
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 40 mg and 60 mg Combined
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-value for Pain Right Now.
	Method	Mixed Models Analysis
	Comments	Covariates: Baseline value of pain right now score, type of Diabetes, Duration of diabetic peripheral neuropathic pain (DPNP).
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.92
	Confidence Interval	(2-Sided) 95%; -1.29 to -0.54
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

8. Secondary Outcome

Title	Change From Baseline in Brief Pain Inventory Severity Scores at Week 12
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. Each question has a total range of scores from 0 to 10.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Patients in the Full Analysis Set Population who had a post-baseline measurement in the variable being presented.

Arm/Group Title	Placebo	Duloxetine 40 mg	Duloxetine 60 mg
Arm/Group Description	placebo comparator taken orally every day	Duloxetine 40 milligrams (mg) taken orally every day	Duloxetine 60 milligrams (mg) taken orally every day
Measure Participants	165	84	85
Worst Pain	-1.62 (0.21)	-2.51 (0.25)	-2.68 (0.25)
Least Pain	-1.13 (0.21)	-1.92 (0.25)	-2.04 (0.25)
Average Pain	-1.55 (0.2)	-2.53 (0.23)	-2.56 (0.23)
Pain Right Now	-1.67 (0.22)	-2.55 (0.25)	-2.62 (0.26)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 40 mg and 60 mg Combined
	Comments	Worst Pain Score analysis
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.89
	Confidence Interval	(2-Sided) 95%; -1.34 to -0.44
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 60 mg
	Comments	Worst Pain Score analysis
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-1.06
	Confidence Interval	(2-Sided) 95%; -1.51 to -0.62
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 40 mg and 60 mg Combined
	Comments	Least Pain Score analysis
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.78
	Confidence Interval	(2-Sided) 95%; -1.23 to -0.33
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 60 mg
	Comments	Least Pain Score analysis
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Mean Squares Difference
	Estimated Value	-0.91
	Confidence Interval	(2-Sided) 95%; -1.36 to -0.46
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 40 mg and 60 mg Combined
	Comments	Average Pain Score analysis
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.98
	Confidence Interval	(2-Sided) 95%; -1.39 to -0.58
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 60 mg
	Comments	Average Pain Score analysis
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-1.01
	Confidence Interval	(2-Sided) 95%; -1.41 to -0.61
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 40 mg and 60 mg Combined
	Comments	Pain Right Now Score analysis
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.88
	Confidence Interval	(2-Sided) 95%; -1.35 to -0.41
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 60 mg
	Comments	Pain Right Now Score analysis
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.95
	Confidence Interval	(2-Sided) 95%; -1.41 to -0.48
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

9. Secondary Outcome

Title	Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 for the Combined Duloxetine Arms (40 mg + 60 mg)
Description	The Interference scores range from 0 (does not interfere) to 10 (completely interferes). There are 7 questions assessing the interference of pain in the past 24 hours for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. Each question has a total range of scores from 0 to 10.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Patients in the Full Analysis Set Population who had a post-baseline measurement in the variable being presented.

Arm/Group Title	Placebo	Duloxetine 40 mg and 60 mg Combined
Arm/Group Description	placebo comparator taken orally every day	Duloxetine 40 milligrams (mg) taken orally every day, and Duloxetine 60 mg taken orally every day.
Measure Participants	165	169
General Activity	-1.88 (0.24)	-2.29 (0.24)
Mood	-1.91 (0.24)	-2.28 (0.24)
Walking Ability	-1.82 (0.23)	-2.31 (0.23)
Normal Work	-1.49 (0.23)	-1.86 (0.23)
Relation to People	-0.77 (0.23)	-1.32 (0.23)
Sleep	-1.69 (0.24)	-2.15 (0.24)
Enjoyment of Life	-1.59 (0.23)	-2.15 (0.23)
Average of Interference Scores	-1.56 (0.2)	-2.04 (0.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 40 mg and 60 mg Combined
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0676
	Comments	P-value for General Activity.
	Method	Mixed Models Analysis
	Comments	Covariates: Baseline value of general activity score, type of Diabetes, Duration of diabetic peripheral neuropathic pain (DPNP).
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.41
	Confidence Interval	(2-Sided) 95%; -0.85 to 0.03
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 40 mg and 60 mg Combined
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0933
	Comments	P-value for Mood.
	Method	Mixed Models Analysis
	Comments	Covariates: Baseline value of mood score, type of Diabetes, Duration of diabetic peripheral neuropathic pain (DPNP).
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.37
	Confidence Interval	(2-Sided) 95%; -0.8 to 0.06
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 40 mg and 60 mg Combined
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0228
	Comments	P-value for Walking Ability.
	Method	Mixed Models Analysis
	Comments	Covariates: Baseline value of walking ability score, type of Diabetes, Duration of diabetic peripheral neuropathic pain (DPNP).
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.49
	Confidence Interval	(2-Sided) 95%; -0.91 to -0.07
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 40 mg and 60 mg Combined
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0783
	Comments	P-value for Normal Work.
	Method	Mixed Models Analysis
	Comments	Covariates: Baseline value of normal work score, type of Diabetes, Duration of diabetic peripheral neuropathic pain (DPNP).
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.38
	Confidence Interval	(2-Sided) 95%; -0.8 to 0.04
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 40 mg and 60 mg Combined
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0076
	Comments	P-value for Relation to People.
	Method	Mixed Models Analysis
	Comments	Covariates: Baseline value of relation to people score, type of Diabetes, Duration of diabetic peripheral neuropathic pain (DPNP).
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.55
	Confidence Interval	(2-Sided) 95%; -0.96 to -0.15
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 40 mg and 60 mg Combined
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0378
	Comments	P-value for Sleep.
	Method	Mixed Models Analysis
	Comments	Covariates: Baseline value of sleep score, type of Diabetes, Duration of diabetic peripheral neuropathic pain (DPNP).
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.46
	Confidence Interval	(2-Sided) 95%; -0.9 to -0.03
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 40 mg and 60 mg Combined
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0089
	Comments	P-value for Enjoyment of Life.
	Method	Mixed Models Analysis
	Comments	Covariates: Baseline value of enjoyment of life score, type of Diabetes, Duration of diabetic peripheral neuropathic pain (DPNP).
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.56
	Confidence Interval	(2-Sided) 95%; -0.98 to -0.14
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 40 mg and 60 mg Combined
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0095
	Comments	P-value for Average of Interference Scores
	Method	Mixed Models Analysis
	Comments	Covariates: Baseline value of average of interference scores, type of Diabetes, Duration of diabetic peripheral neuropathic pain (DPNP).
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.48
	Confidence Interval	(2-Sided) 95%; -0.85 to -0.12
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

10. Secondary Outcome

Title	Change From Baseline in Brief Pain Inventory Interference Scores at Week 12
Description	The Interference scores range from 0 (does not interfere) to 10 (completely interferes). There are 7 questions assessing the interference of pain in the past 24 hours for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. Each question has a total range of scores from 0 to 10.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Patients in the Full Analysis Set Population who had a post-baseline measurement in the variable being presented.

Arm/Group Title	Placebo	Duloxetine 40 mg	Duloxetine 60 mg
Arm/Group Description	placebo comparator taken orally every day	Duloxetine 40 milligrams (mg) taken orally every day	Duloxetine 60 milligrams (mg) taken orally every day
Measure Participants	165	84	85
General Activity	-1.88 (0.24)	-2.48 (0.29)	-2.1 (0.29)
Mood	-1.91 (0.24)	-2.18 (0.29)	-2.39 (0.29)
Walking Ability	-1.82 (0.23)	-2.32 (0.28)	-2.31 (0.28)
Normal Work	-1.49 (0.23)	-1.84 (0.28)	-1.9 (0.28)
Relation to People	-0.77 (0.23)	-1.16 (0.27)	-1.49 (0.27)
Sleep	-1.69 (0.24)	-2.26 (0.29)	-2.05 (0.29)
Enjoyment of Life	-1.59 (0.23)	-1.96 (0.28)	-2.35 (0.28)
Average of Interference Scores	-1.56 (0.2)	-2 (0.24)	-2.08 (0.24)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 40 mg and 60 mg Combined
	Comments	General Activity score analysis
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -1.14 to -0.06
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 60 mg
	Comments	General Activity score analysis
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.23
	Confidence Interval	(2-Sided) 95%; -0.77 to 0.32
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 40 mg and 60 mg Combined
	Comments	Mood score analysis
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.27
	Confidence Interval	(2-Sided) 95%; -0.8 to 0.27
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 60 mg
	Comments	Mood score analysis
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.48
	Confidence Interval	(2-Sided) 95%; -1.01 to 0.05
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 40 mg and 60 mg Combined
	Comments	Walking Ability score analysis
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -1.02 to 0.02
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 60 mg
	Comments	Walking Ability score analysis
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.49
	Confidence Interval	(2-Sided) 95%; -1.01 to 0.03
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 40 mg and 60 mg Combined
	Comments	Normal Work score analysis
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.35
	Confidence Interval	(2-Sided) 95%; -0.86 to 0.16
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 60 mg
	Comments	Normal Work score analysis
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.41
	Confidence Interval	(2-Sided) 95%; -0.92 to 0.11
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 40 mg and 60 mg Combined
	Comments	Relation to People score analysis
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.39
	Confidence Interval	(2-Sided) 95%; -0.89 to 0.11
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 60 mg
	Comments	Relation to People score analysis
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.71
	Confidence Interval	(2-Sided) 95%; -1.21 to -0.22
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 40 mg and 60 mg Combined
	Comments	Sleep score analysis
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.57
	Confidence Interval	(2-Sided) 95%; -1.11 to -0.03
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 60 mg
	Comments	Sleep score analysis
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.36
	Confidence Interval	(2-Sided) 95%; -0.9 to 0.18
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 40 mg and 60 mg Combined
	Comments	Enjoyment of Life score analysis
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.37
	Confidence Interval	(2-Sided) 95%; -0.88 to 0.15
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 60 mg
	Comments	Enjoyment of Life score analysis
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.76
	Confidence Interval	(2-Sided) 95%; -1.27 to -0.24
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 40 mg and 60 mg Combined
	Comments	Average of Interference scores analysis
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.45
	Confidence Interval	(2-Sided) 95%; -0.9 to 0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 60 mg
	Comments	Average of Interference scores analysis
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.52
	Confidence Interval	(2-Sided) 95%; -0.97 to -0.07
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

11. Secondary Outcome

Title	Change From Baseline in Beck Depression Inventory-II (BDI-II) Total Score at Week 12 for the Combined Duloxetine Arms (40 mg + 60 mg)
Description	A 21-item, patient-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 four-point scale for each item ranging from 0 to 3. Total score ranges from 0 (no depression) to 63 (severe depression).
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Patients in the Full Analysis Set Population who had a post-baseline measurement in the variable being presented.

Arm/Group Title	Placebo	Duloxetine 40 mg and 60 mg Combined
Arm/Group Description	placebo comparator taken orally every day	Duloxetine 40 milligrams (mg) taken orally every day, and Duloxetine 60 mg taken orally every day.
Measure Participants	165	169
Least Squares Mean (Standard Error) [units on a scale]	-3.27 (0.64)	-3.37 (0.64)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 40 mg and 60 mg Combined
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8517
	Comments
	Method	Mixed Models Analysis
	Comments	Covariates: Baseline value of BDI-II, type of diabetes, and duration of diabetic peripheral neuropathic pain (DPNP).
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.11
	Confidence Interval	(2-Sided) 95%; -1.22 to 1.01
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

12. Secondary Outcome

Title	Change From Baseline in Beck Depression Inventory-II (BDI-II) Total Score at Week 12
Description	A 21-item, patient-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 four-point scale for each item ranging from 0 to 3. Total score ranges from 0 (no depression) to 63 (severe depression).
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Patients in the Full Analysis Set Population who had a post-baseline measurement in the variable being presented.

Arm/Group Title	Placebo	Duloxetine 40 mg	Duloxetine 60 mg
Arm/Group Description	placebo comparator taken orally every day	Duloxetine 40 milligrams (mg) taken orally every day	Duloxetine 60 milligrams (mg) taken orally every day
Measure Participants	165	84	85
Least Squares Mean (Standard Error) [units on a scale]	-3.28 (0.65)	-2.94 (0.76)	-3.83 (0.77)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 40 mg and 60 mg Combined
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	0.34
	Confidence Interval	(2-Sided) 95%; -1.03 to 1.71
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Duloxetine 60 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.55
	Confidence Interval	(2-Sided) 95%; -1.92 to 0.81
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean Difference = Duloxetine 40 mg and 60 mg Combined minus Placebo.

Adverse Events

Arm/Group Title	Placebo		Duloxetine 40 mg		Duloxetine 60 mg
Arm/Group Description	placebo comparator taken orally every day		Duloxetine 40 milligrams (mg) taken orally every day		Duloxetine 60 milligrams (mg) taken orally every day
All Cause Mortality
	Placebo		Duloxetine 40 mg		Duloxetine 60 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Duloxetine 40 mg		Duloxetine 60 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/167 (3.6%)		3/85 (3.5%)		2/86 (2.3%)
Hepatobiliary disorders
Hepatic function abnormal	1/167 (0.6%)	1	0/85 (0%)	0	0/86 (0%)	0
Infections and infestations
Arthritis bacterial	1/167 (0.6%)	1	0/85 (0%)	0	0/86 (0%)	0
Epiglottitis	0/167 (0%)	0	0/85 (0%)	0	1/86 (1.2%)	1
Osteomyelitis	1/167 (0.6%)	1	0/85 (0%)	0	0/86 (0%)	0
Sepsis	1/167 (0.6%)	1	0/85 (0%)	0	0/86 (0%)	0
Tuberculous pleurisy	1/167 (0.6%)	1	0/85 (0%)	0	0/86 (0%)	0
Injury, poisoning and procedural complications
Alcohol poisoning	0/167 (0%)	0	1/85 (1.2%)	1	0/86 (0%)	0
Back injury	1/167 (0.6%)	1	0/85 (0%)	0	0/86 (0%)	0
Contusion	0/167 (0%)	0	1/85 (1.2%)	1	0/86 (0%)	0
Ulna fracture	0/167 (0%)	0	1/85 (1.2%)	1	0/86 (0%)	0
Investigations
Blood alkaline phosphatase increased	1/167 (0.6%)	1	0/85 (0%)	0	0/86 (0%)	0
Blood bilirubin increased	1/167 (0.6%)	1	0/85 (0%)	0	0/86 (0%)	0
C-reactive protein increased	1/167 (0.6%)	1	0/85 (0%)	0	0/86 (0%)	0
Gamma-glutamyltransferase increased	1/167 (0.6%)	1	0/85 (0%)	0	0/86 (0%)	0
Platelet count increased	1/167 (0.6%)	1	0/85 (0%)	0	0/86 (0%)	0
Urine albumin/creatinine ratio increased	1/167 (0.6%)	1	0/85 (0%)	0	0/86 (0%)	0
Metabolism and nutrition disorders
Hypoglycaemia	0/167 (0%)	0	1/85 (1.2%)	1	0/86 (0%)	0
Musculoskeletal and connective tissue disorders
Pathological fracture	1/167 (0.6%)	1	0/85 (0%)	0	0/86 (0%)	0
Nervous system disorders
Cerebral infarction	1/167 (0.6%)	1	0/85 (0%)	0	0/86 (0%)	0
Facial palsy	1/167 (0.6%)	1	0/85 (0%)	0	0/86 (0%)	0
Hemiparesis	1/167 (0.6%)	1	0/85 (0%)	0	0/86 (0%)	0
Radiculopathy	0/167 (0%)	0	0/85 (0%)	0	1/86 (1.2%)	1
Thalamus haemorrhage	1/167 (0.6%)	1	0/85 (0%)	0	0/86 (0%)	0
Psychiatric disorders
Self injurious behaviour	0/167 (0%)	0	0/85 (0%)	0	1/86 (1.2%)	1
Renal and urinary disorders
Renal failure acute	1/167 (0.6%)	1	0/85 (0%)	0	0/86 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		Duloxetine 40 mg		Duloxetine 60 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	121/167 (72.5%)		71/85 (83.5%)		73/86 (84.9%)
Ear and labyrinth disorders
Tinnitus	0/167 (0%)	0	4/85 (4.7%)	4	1/86 (1.2%)	1
Gastrointestinal disorders
Constipation	9/167 (5.4%)	9	6/85 (7.1%)	6	5/86 (5.8%)	6
Diarrhoea	6/167 (3.6%)	6	4/85 (4.7%)	5	7/86 (8.1%)	7
Nausea	3/167 (1.8%)	3	10/85 (11.8%)	11	14/86 (16.3%)	17
Stomach discomfort	4/167 (2.4%)	4	3/85 (3.5%)	4	4/86 (4.7%)	4
Vomiting	2/167 (1.2%)	2	4/85 (4.7%)	5	5/86 (5.8%)	7
General disorders
Malaise	3/167 (1.8%)	3	3/85 (3.5%)	3	6/86 (7%)	7
Thirst	3/167 (1.8%)	3	4/85 (4.7%)	4	4/86 (4.7%)	4
Infections and infestations
Nasopharyngitis	24/167 (14.4%)	24	10/85 (11.8%)	11	14/86 (16.3%)	16
Investigations
Alanine aminotransferase increased	6/167 (3.6%)	6	5/85 (5.9%)	5	5/86 (5.8%)	5
Aspartate aminotransferase increased	6/167 (3.6%)	6	5/85 (5.9%)	5	8/86 (9.3%)	8
Blood alkaline phosphatase increased	1/167 (0.6%)	1	4/85 (4.7%)	4	2/86 (2.3%)	2
Blood creatine phosphokinase increased	6/167 (3.6%)	6	6/85 (7.1%)	6	0/86 (0%)	0
Blood glucose decreased	7/167 (4.2%)	15	2/85 (2.4%)	4	2/86 (2.3%)	2
Blood lactate dehydrogenase increased	4/167 (2.4%)	4	2/85 (2.4%)	2	5/86 (5.8%)	5
Gamma-glutamyltransferase increased	4/167 (2.4%)	4	2/85 (2.4%)	2	5/86 (5.8%)	5
Glycosylated haemoglobin increased	4/167 (2.4%)	4	1/85 (1.2%)	1	5/86 (5.8%)	5
White blood cell count increased	4/167 (2.4%)	4	4/85 (4.7%)	4	5/86 (5.8%)	5
Metabolism and nutrition disorders
Decreased appetite	0/167 (0%)	0	1/85 (1.2%)	1	4/86 (4.7%)	4
Nervous system disorders
Dizziness	2/167 (1.2%)	3	6/85 (7.1%)	8	4/86 (4.7%)	4
Headache	6/167 (3.6%)	9	4/85 (4.7%)	4	2/86 (2.3%)	3
Somnolence	14/167 (8.4%)	14	16/85 (18.8%)	16	21/86 (24.4%)	23
Skin and subcutaneous tissue disorders
Eczema	5/167 (3%)	5	4/85 (4.7%)	4	1/86 (1.2%)	1
Vascular disorders
Orthostatic hypotension	1/167 (0.6%)	1	1/85 (1.2%)	1	4/86 (4.7%)	4

Limitations/Caveats

The protocol-specified primary analyses for this study were comparisons between combined duloxetine arms (40 mg + 60 mg) and placebo. The study was powered on combined duloxetine arms and statistical comparisons were not performed among single arms.

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.