Trial Outcomes & Findings for A Study Comparing Duloxetine Versus Placebo in Patients Taking a Nonsteroidal Anti-inflammatory Drug (NSAID) for Knee Pain Due to Osteoarthritis (NCT NCT01018680)

Last Updated: 2012-10-05

Results Overview

The weekly mean 24-hour average pain score was calculated from the participant's daily 24-hour average pain ratings using an 11-point numeric rating scale, with scores from 0 (indicating "no pain") to 10 (indicating "the worst possible pain"). The Least Squares Mean estimates were adjusted for baseline, treatment, investigator (pooled), week, treatment\*week, and baseline\*week.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

524 participants

Primary outcome timeframe

Baseline, 8 weeks (blinded endpoint)

Results posted on

2012-10-05

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Participants received placebo by mouth, once daily for 10 weeks.	Duloxetine Participants initially received 30 milligrams (mg) duloxetine by mouth, once daily for 1 week, followed by 60 mg by mouth, once daily thereafter. At end of 3 weeks, participants with a weekly mean 24-hour average pain value ≥4 in week preceding their visit had their dose escalated up to 120 mg by mouth, once daily until Week 10.
Overall Study STARTED	260	264
Overall Study COMPLETED	199	189
Overall Study NOT COMPLETED	61	75

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received placebo by mouth, once daily for 10 weeks.	Duloxetine Participants initially received 30 milligrams (mg) duloxetine by mouth, once daily for 1 week, followed by 60 mg by mouth, once daily thereafter. At end of 3 weeks, participants with a weekly mean 24-hour average pain value ≥4 in week preceding their visit had their dose escalated up to 120 mg by mouth, once daily until Week 10.
Overall Study Adverse Event	23	40
Overall Study Withdrawal by Subject	10	10
Overall Study Protocol Violation	5	8
Overall Study Sponsor Decision	6	7
Overall Study Lack of Efficacy	8	2
Overall Study Lost to Follow-up	5	3
Overall Study Entry Criteria Not Met	1	4
Overall Study Physician Decision	3	1

Baseline Characteristics

A Study Comparing Duloxetine Versus Placebo in Patients Taking a Nonsteroidal Anti-inflammatory Drug (NSAID) for Knee Pain Due to Osteoarthritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=260 Participants Participants received placebo by mouth, once daily for 10 weeks.	Duloxetine n=264 Participants Participants initially received 30 milligrams (mg) duloxetine by mouth, once daily for 1 week, followed by 60 mg by mouth, once daily thereafter. At end of 3 weeks, participants with a weekly mean 24-hour average pain value ≥4 in week preceding their visit had their dose escalated up to 120 mg by mouth, once daily until Week 10.	Total n=524 Participants Total of all reporting groups
Age Continuous	60.32 years STANDARD_DEVIATION 9.17 • n=5 Participants	61.63 years STANDARD_DEVIATION 9.24 • n=7 Participants	60.98 years STANDARD_DEVIATION 9.22 • n=5 Participants
Sex: Female, Male Female	147 Participants n=5 Participants	152 Participants n=7 Participants	299 Participants n=5 Participants
Sex: Female, Male Male	113 Participants n=5 Participants	112 Participants n=7 Participants	225 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	46 Participants n=5 Participants	38 Participants n=7 Participants	84 Participants n=5 Participants
Race (NIH/OMB) White	206 Participants n=5 Participants	218 Participants n=7 Participants	424 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	260 participants n=5 Participants	264 participants n=7 Participants	524 participants n=5 Participants
Weight	90.78 kilograms (kg) STANDARD_DEVIATION 17.49 • n=5 Participants	90.41 kilograms (kg) STANDARD_DEVIATION 18.13 • n=7 Participants	90.59 kilograms (kg) STANDARD_DEVIATION 17.80 • n=5 Participants
Weekly 24-Hour Average Pain Rating	6.36 units on a scale STANDARD_DEVIATION 1.41 • n=5 Participants	6.27 units on a scale STANDARD_DEVIATION 1.41 • n=7 Participants	6.32 units on a scale STANDARD_DEVIATION 1.41 • n=5 Participants
Brief Pain Inventory-Severity (BPI-S) Average Pain	6.24 units on a scale STANDARD_DEVIATION 1.51 • n=5 Participants	6.09 units on a scale STANDARD_DEVIATION 1.58 • n=7 Participants	6.16 units on a scale STANDARD_DEVIATION 1.54 • n=5 Participants
Patient Global Assessment of Illness (PGAI)	6.95 units on a scale STANDARD_DEVIATION 1.50 • n=5 Participants	6.93 units on a scale STANDARD_DEVIATION 1.49 • n=7 Participants	6.94 units on a scale STANDARD_DEVIATION 1.49 • n=5 Participants
Western Ontario and McMaster Universities Index of Osteoarthritis Physical Function Score	37.51 units on a scale STANDARD_DEVIATION 9.39 • n=5 Participants	37.40 units on a scale STANDARD_DEVIATION 10.10 • n=7 Participants	37.45 units on a scale STANDARD_DEVIATION 9.74 • n=5 Participants
Duration of Osteoarthritis (OA) Pain	9.19 years STANDARD_DEVIATION 8.92 • n=5 Participants	9.79 years STANDARD_DEVIATION 8.88 • n=7 Participants	9.49 years STANDARD_DEVIATION 8.90 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 8 weeks (blinded endpoint)

Population: Modified intent to treat (mITT) population: ITT participants with a baseline and at least 1 post-baseline weekly mean 24-hour average pain value were included in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=255 Participants Participants received placebo by mouth, once daily for 10 weeks.	Duloxetine n=259 Participants Participants initially received 30 milligrams (mg) duloxetine by mouth, once daily for 1 week, followed by 60 mg by mouth, once daily thereafter. At end of 3 weeks, participants with a weekly mean 24-hour average pain value ≥4 in week preceding their visit had their dose escalated up to 120 mg by mouth, once daily until Week 10.
Change From Baseline in the Weekly Mean of the 24-Hour Average Pain Score at 8 Weeks	-1.55 units on a scale Standard Error 0.11	-2.46 units on a scale Standard Error 0.11

SECONDARY outcome

Timeframe: 8 weeks (blinded endpoint)

Population: Modified intent to treat (mITT) population: ITT participants with a baseline PGI-S rating and at least 1 post-baseline PGI-I rating were included in the analysis.

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). The Least Squares Mean estimates were adjusted for baseline value of Patient Global Impression of Severity (PGI-S), treatment, investigator (pooled), visit, and treatment\*visit. The PGI-S measures participant's perception of severity of illness at the time of assessment. Scores range from 1 (normal, not at all ill) to 7 (extremely ill).

Outcome measures

Outcome measures
Measure	Placebo n=254 Participants Participants received placebo by mouth, once daily for 10 weeks.	Duloxetine n=254 Participants Participants initially received 30 milligrams (mg) duloxetine by mouth, once daily for 1 week, followed by 60 mg by mouth, once daily thereafter. At end of 3 weeks, participants with a weekly mean 24-hour average pain value ≥4 in week preceding their visit had their dose escalated up to 120 mg by mouth, once daily until Week 10.
Patient Global Impression of Improvement (PGI-I) at 8 Weeks	2.93 units on a scale Standard Error 0.09	2.33 units on a scale Standard Error 0.09

SECONDARY outcome

Timeframe: Baseline, 8 weeks (blinded endpoint)

Population: Modified intent to treat (mITT) population: ITT participants with a baseline and at least 1 post-baseline WOMAC value were included in the analysis.

Self-administered questionnaire captures elements of pain, stiffness, and physical disability in participants with osteoarthritis of the knee and/or hip. Index has 24 questions (5 on pain, 2 on stiffness, 17 on physical function). Each question uses a 5-point numeric rating scale ranging from 0 (none) to 4 (extreme). Pain scores range: 0 to 20. Stiffness scores range: 0 to 8. Physical function scores range: 0 to 68. Higher scores=greater impairment. Least Squares Mean estimates were adjusted for baseline value, treatment, investigator (pooled), visit, treatment\*visit, and baseline value\*visit.

Outcome measures

Outcome measures
Measure	Placebo n=256 Participants Participants received placebo by mouth, once daily for 10 weeks.	Duloxetine n=258 Participants Participants initially received 30 milligrams (mg) duloxetine by mouth, once daily for 1 week, followed by 60 mg by mouth, once daily thereafter. At end of 3 weeks, participants with a weekly mean 24-hour average pain value ≥4 in week preceding their visit had their dose escalated up to 120 mg by mouth, once daily until Week 10.
Change From Baseline in the Western Ontario and McMaster Universities Index of Osteoarthritis (WOMAC) Pain, Stiffness, and Physical Function Subscale Scores at 8 Weeks WOMAC Physical Disability Score (n=253, 251)	-10.25 units on a scale Standard Error 0.82	-15.09 units on a scale Standard Error 0.81
Change From Baseline in the Western Ontario and McMaster Universities Index of Osteoarthritis (WOMAC) Pain, Stiffness, and Physical Function Subscale Scores at 8 Weeks WOMAC Pain Score	-3.13 units on a scale Standard Error 0.24	-4.41 units on a scale Standard Error 0.23
Change From Baseline in the Western Ontario and McMaster Universities Index of Osteoarthritis (WOMAC) Pain, Stiffness, and Physical Function Subscale Scores at 8 Weeks WOMAC Stiffness Score	-1.45 units on a scale Standard Error 0.12	-1.88 units on a scale Standard Error 0.11

SECONDARY outcome

Timeframe: Baseline, 8 weeks (blinded endpoint)

Population: Modified intent to treat (mITT) population: ITT participants with a baseline night/worst pain value and at least 1 post-baseline weekly mean 24-hour night/worst pain value were included in the analysis.

Weekly mean 24-hour night pain and worst pain values are calculated from the participant's daily assessments of pain at night and worst pain during the previous 24 hours on an 11-point numeric rating scale, with scores from 0 (indicating "no pain") to 10 (indicating "the worst possible pain"). The Least Squares Mean estimates were adjusted for baseline value, treatment, investigator (pooled), week, treatment\*week, and baseline\*week.

Outcome measures

Outcome measures
Measure	Placebo n=253 Participants Participants received placebo by mouth, once daily for 10 weeks.	Duloxetine n=259 Participants Participants initially received 30 milligrams (mg) duloxetine by mouth, once daily for 1 week, followed by 60 mg by mouth, once daily thereafter. At end of 3 weeks, participants with a weekly mean 24-hour average pain value ≥4 in week preceding their visit had their dose escalated up to 120 mg by mouth, once daily until Week 10.
Change From Baseline in the Weekly Mean of the 24-Hour Night Pain and Worst Pain Scores at 8 Weeks Night Pain Intensity	-1.46 units on a scale Standard Error 0.11	-2.26 units on a scale Standard Error 0.11
Change From Baseline in the Weekly Mean of the 24-Hour Night Pain and Worst Pain Scores at 8 Weeks Worst Pain Intensity	-1.58 units on a scale Standard Error 0.13	-2.61 units on a scale Standard Error 0.13

SECONDARY outcome

Timeframe: Baseline, 8 weeks (blinded endpoint)

Population: Modified intent to treat (mITT) population: ITT participants with a baseline and at least 1 post-baseline BPI-S/BPI-I value were included in the analysis.

Measures pain severity and pain interference with function. Severity scores: 0 (no pain) to 10 (severe pain) on each question. Interference scores: 0 (does not interfere) to 10 (completely interferes) on each question assessing interference of pain in past 24 hours for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. Mean interference is the average across the 7 interference items. The Least Squares Mean estimates were adjusted for baseline value, treatment, investigator (pooled), visit, treatment\*visit, and baseline\*visit.

Outcome measures

Outcome measures
Measure	Placebo n=256 Participants Participants received placebo by mouth, once daily for 10 weeks.	Duloxetine n=258 Participants Participants initially received 30 milligrams (mg) duloxetine by mouth, once daily for 1 week, followed by 60 mg by mouth, once daily thereafter. At end of 3 weeks, participants with a weekly mean 24-hour average pain value ≥4 in week preceding their visit had their dose escalated up to 120 mg by mouth, once daily until Week 10.
Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) Scores at 8 Weeks BPI-I for Mood	-1.80 units on a scale Standard Error 0.15	-2.52 units on a scale Standard Error 0.15
Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) Scores at 8 Weeks BPI-I for Walking Ability	-1.85 units on a scale Standard Error 0.17	-2.80 units on a scale Standard Error 0.17
Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) Scores at 8 Weeks BPI-I for Normal Work	-1.92 units on a scale Standard Error 0.17	-2.77 units on a scale Standard Error 0.17
Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) Scores at 8 Weeks BPI-I for Relations with Others (n=255, 258)	-1.25 units on a scale Standard Error 0.14	-1.94 units on a scale Standard Error 0.14
Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) Scores at 8 Weeks BPI-I for Sleep	-2.01 units on a scale Standard Error 0.14	-2.69 units on a scale Standard Error 0.14
Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) Scores at 8 Weeks BPI-I for Enjoyment of Life	-1.89 units on a scale Standard Error 0.17	-2.66 units on a scale Standard Error 0.17
Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) Scores at 8 Weeks BPI-I for Mean Interference Score	-1.77 units on a scale Standard Error 0.14	-2.60 units on a scale Standard Error 0.14
Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) Scores at 8 Weeks BPI-S for Worst Pain	-1.87 units on a scale Standard Error 0.17	-2.94 units on a scale Standard Error 0.17
Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) Scores at 8 Weeks BPI-S for Least Pain	-1.44 units on a scale Standard Error 0.14	-2.14 units on a scale Standard Error 0.14
Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) Scores at 8 Weeks BPI-S for Average Pain	-1.78 units on a scale Standard Error 0.15	-2.73 units on a scale Standard Error 0.15
Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) Scores at 8 Weeks BPI-S for Pain Right Now	-2.03 units on a scale Standard Error 0.16	-2.74 units on a scale Standard Error 0.16
Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) Scores at 8 Weeks BPI-I for General Activity	-1.79 units on a scale Standard Error 0.17	-2.76 units on a scale Standard Error 0.16

SECONDARY outcome

Timeframe: Baseline, 8 weeks (blinded endpoint)

Population: Modified intent to treat (mITT) population: ITT participants with a baseline and at least 1 post-baseline CGI-S value were included in the analysis.

The CGI-S scale evaluates the severity of illness at the time of assessment. The scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). The CGI-S must be administered by a study physician in the presence of the participant or after having been in the presence of the participant. The Least Squares Mean estimates were adjusted for baseline, treatment, investigator (pooled), visit, treatment\*visit, and baseline\*visit.

Outcome measures

Outcome measures
Measure	Placebo n=244 Participants Participants received placebo by mouth, once daily for 10 weeks.	Duloxetine n=247 Participants Participants initially received 30 milligrams (mg) duloxetine by mouth, once daily for 1 week, followed by 60 mg by mouth, once daily thereafter. At end of 3 weeks, participants with a weekly mean 24-hour average pain value ≥4 in week preceding their visit had their dose escalated up to 120 mg by mouth, once daily until Week 10.
Change From Baseline in the Clinical Global Impression of Severity (CGI-S) at 8 Weeks	-0.80 units on a scale Standard Error 0.07	-1.16 units on a scale Standard Error 0.07

SECONDARY outcome

Timeframe: Baseline, 8 weeks (blinded endpoint)

Population: Modified intent to treat (mITT) population: ITT participants with a baseline and at least 1 post-baseline PGAI value were included in the analysis.

The PGAI is a participant-rated measure of the severity of osteoarthritis (OA) of the knee the participant has experienced in the past week as indicated on an 11-point numeric rating scale, with scores ranging from 0 to 10, where greater numbers reflect greater severity. The Least Squares Mean estimates were adjusted for baseline value, treatment, investigator (pooled), visit, treatment\*visit, and baseline\*visit.

Outcome measures

Outcome measures
Measure	Placebo n=219 Participants Participants received placebo by mouth, once daily for 10 weeks.	Duloxetine n=214 Participants Participants initially received 30 milligrams (mg) duloxetine by mouth, once daily for 1 week, followed by 60 mg by mouth, once daily thereafter. At end of 3 weeks, participants with a weekly mean 24-hour average pain value ≥4 in week preceding their visit had their dose escalated up to 120 mg by mouth, once daily until Week 10.
Change From Baseline in the Patient Global Assessment of Illness (PGAI) at 8 Weeks	-1.77 units on a scale Standard Error 0.17	-2.95 units on a scale Standard Error 0.17

SECONDARY outcome

Timeframe: Baseline, 8 weeks (blinded endpoint)

Population: Modified intent to treat (mITT) population: ITT participants with a baseline and at least 1 post-baseline BPOMS value were included in the analysis.

30-item BPOMS measures positive and negative aspects of mood states (item score: 0=not at all to 4=extremely). 5 negative factors: tension-anxiety, depression-dejection, anger-hostility, fatigue-inertia, confusion-bewilderment; 1 positive factor: vigor-activity. Factor scores range: 0 to 20; high scores=negative mood (positive mood for vigor). Total score=sum of 5 negative factor scores minus vigor score; range: -20=least disturbed to 100=most disturbed. Least Squares Mean estimates adjusted for baseline value, treatment, investigator (pooled), visit, treatment\*visit, and baseline value\*visit.

Outcome measures

Outcome measures
Measure	Placebo n=220 Participants Participants received placebo by mouth, once daily for 10 weeks.	Duloxetine n=216 Participants Participants initially received 30 milligrams (mg) duloxetine by mouth, once daily for 1 week, followed by 60 mg by mouth, once daily thereafter. At end of 3 weeks, participants with a weekly mean 24-hour average pain value ≥4 in week preceding their visit had their dose escalated up to 120 mg by mouth, once daily until Week 10.
Change From Baseline in the Profile of Mood States-Brief Form (BPOMS) Total and Subscale Scores at 8 Weeks BPOMS Total Score	-4.15 units on a scale Standard Error 0.89	-4.98 units on a scale Standard Error 0.88
Change From Baseline in the Profile of Mood States-Brief Form (BPOMS) Total and Subscale Scores at 8 Weeks BPOMS Tension-Anxiety Score	-0.90 units on a scale Standard Error 0.21	-1.17 units on a scale Standard Error 0.20
Change From Baseline in the Profile of Mood States-Brief Form (BPOMS) Total and Subscale Scores at 8 Weeks BPOMS Depression-Dejection Score	-0.51 units on a scale Standard Error 0.21	-0.85 units on a scale Standard Error 0.20
Change From Baseline in the Profile of Mood States-Brief Form (BPOMS) Total and Subscale Scores at 8 Weeks BPOMS Anger-Hostility Score	-0.63 units on a scale Standard Error 0.21	-1.15 units on a scale Standard Error 0.21
Change From Baseline in the Profile of Mood States-Brief Form (BPOMS) Total and Subscale Scores at 8 Weeks BPOMS Vigor-Activity Score	-0.34 units on a scale Standard Error 0.33	0.04 units on a scale Standard Error 0.32
Change From Baseline in the Profile of Mood States-Brief Form (BPOMS) Total and Subscale Scores at 8 Weeks BPOMS Fatigue-Inertia Score	-1.40 units on a scale Standard Error 0.30	-1.47 units on a scale Standard Error 0.29
Change From Baseline in the Profile of Mood States-Brief Form (BPOMS) Total and Subscale Scores at 8 Weeks BPOMS Confusion-Bewilderment Score	-0.29 units on a scale Standard Error 0.17	-0.32 units on a scale Standard Error 0.17

SECONDARY outcome

Timeframe: Baseline through 10 weeks (blinded endpoint)

Population: Modified intent to treat (mITT) population: ITT participants with a baseline and at least 1 post-baseline weekly acetaminophen use value were included in the analysis.

The Least Squares (LS) Mean percentage estimates of participants using acetaminophen was determined during each week individually over the full 10-week treatment period based on participant's daily Yes/No assessments for the use of acetaminophen. The LS Mean estimates for the main effect of treatment (average weekly use) were adjusted for baseline value, treatment, investigator (pooled), week, and treatment\*week.

Outcome measures

Outcome measures
Measure	Placebo n=258 Participants Participants received placebo by mouth, once daily for 10 weeks.	Duloxetine n=262 Participants Participants initially received 30 milligrams (mg) duloxetine by mouth, once daily for 1 week, followed by 60 mg by mouth, once daily thereafter. At end of 3 weeks, participants with a weekly mean 24-hour average pain value ≥4 in week preceding their visit had their dose escalated up to 120 mg by mouth, once daily until Week 10.
Percentage of Participants Using Acetaminophen Weekly During the 10-Week Treatment Period	26 percentage of participants Standard Error 2	22 percentage of participants Standard Error 2

SECONDARY outcome

Timeframe: Up to 8 weeks (blinded endpoint)

Population: Modified intent to treat (mITT) population: ITT participants with a baseline and at least 1 post-baseline OARSI response value, last-observation-carried forward (LOCF) based on values of each of the 3 components listed in the outcome measure description were included in the analysis.

OARSI response is composite Yes/No response assessed at 8 weeks based on decrease in 24-hour average pain ratings, range: 0 ("no pain") to 10 ("worst possible pain"), improvement in functioning (using WOMAC physical function scores, range: 0 \[no difficulty\] to 68 \[extreme difficulty\]), and improvement in participant's impression of illness (using PGAI scores, range: 0 to 10; 10=greatest severity). OARSI responder=large response in pain or function components (50% relative and 20% absolute improvement), or moderate response (20% relative and 10% absolute improvement) in 2 of 3 components.

Outcome measures

Outcome measures
Measure	Placebo n=259 Participants Participants received placebo by mouth, once daily for 10 weeks.	Duloxetine n=263 Participants Participants initially received 30 milligrams (mg) duloxetine by mouth, once daily for 1 week, followed by 60 mg by mouth, once daily thereafter. At end of 3 weeks, participants with a weekly mean 24-hour average pain value ≥4 in week preceding their visit had their dose escalated up to 120 mg by mouth, once daily until Week 10.
Percentage of Responders as Assessed by the Osteoarthritis Research Society International (OARSI) Response Criteria up to 8 Weeks	48.3 percentage of responders	69.6 percentage of responders

SECONDARY outcome

Timeframe: Up to 8 weeks (blinded endpoint)

Population: Modified intent to treat (mITT) population: ITT participants with a baseline and at least 1 post-baseline weekly mean of the 24-hour average pain score value, last-observation-carried forward (LOCF) were included in the analysis.

Response is a dichotomous outcome (Yes/No) indicating at least 30% (or 50%) reduction from baseline to endpoint for the weekly mean of the 24-hour average pain ratings. The weekly mean 24-hour average pain score was calculated from the participant's daily 24-hour average pain rating assessed on an 11-point numeric rating scale, with scores from 0 ("no pain") to 10 ("worst possible pain").

Outcome measures

Outcome measures
Measure	Placebo n=255 Participants Participants received placebo by mouth, once daily for 10 weeks.	Duloxetine n=259 Participants Participants initially received 30 milligrams (mg) duloxetine by mouth, once daily for 1 week, followed by 60 mg by mouth, once daily thereafter. At end of 3 weeks, participants with a weekly mean 24-hour average pain value ≥4 in week preceding their visit had their dose escalated up to 120 mg by mouth, once daily until Week 10.
Percentage of Participants Who Achieved a 30 Percent or 50 Percent Reduction in the Weekly Mean of the 24-Hour Average Pain Score up to 8 Weeks 30% Response (LOCF) based on 24-Hour Average Pain	33.7 percentage of participants	53.7 percentage of participants
Percentage of Participants Who Achieved a 30 Percent or 50 Percent Reduction in the Weekly Mean of the 24-Hour Average Pain Score up to 8 Weeks 50% Response (LOCF) based on 24-Hour Average Pain	16.1 percentage of participants	35.5 percentage of participants

SECONDARY outcome

Timeframe: Up to 8 weeks (blinded endpoint)

Population: Modified intent to treat (mITT) population: ITT participants with a baseline and at least 1 post-baseline BPI-S average pain value, last-observation-carried forward (LOCF) were included in the analysis.

Response is a dichotomous outcome (Yes/No) indicating at least 30% (or 50%) reduction from baseline to endpoint for BPI-S average pain rating. The BPI-S self-reported scale that measures the severity of pain based on the average pain experienced over the past 24 hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine).

Outcome measures

Outcome measures
Measure	Placebo n=256 Participants Participants received placebo by mouth, once daily for 10 weeks.	Duloxetine n=258 Participants Participants initially received 30 milligrams (mg) duloxetine by mouth, once daily for 1 week, followed by 60 mg by mouth, once daily thereafter. At end of 3 weeks, participants with a weekly mean 24-hour average pain value ≥4 in week preceding their visit had their dose escalated up to 120 mg by mouth, once daily until Week 10.
Percentage of Participants Who Achieved a 30 Percent or 50 Percent Reduction in the Brief Pain Inventory-Severity (BPI-S) Average Pain Score up to 8 Weeks 30% Response (LOCF) based on BPI-S Average Pain	34.0 percentage of participants	58.1 percentage of participants
Percentage of Participants Who Achieved a 30 Percent or 50 Percent Reduction in the Brief Pain Inventory-Severity (BPI-S) Average Pain Score up to 8 Weeks 50% Response (LOCF) based on BPI-S Average Pain	21.1 percentage of participants	45.7 percentage of participants

SECONDARY outcome

Timeframe: Baseline through 10 weeks

Population: All randomized participants were included in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=260 Participants Participants received placebo by mouth, once daily for 10 weeks.	Duloxetine n=264 Participants Participants initially received 30 milligrams (mg) duloxetine by mouth, once daily for 1 week, followed by 60 mg by mouth, once daily thereafter. At end of 3 weeks, participants with a weekly mean 24-hour average pain value ≥4 in week preceding their visit had their dose escalated up to 120 mg by mouth, once daily until Week 10.
Percentage of Participants Who Discontinued Due to an Adverse Event During the 10-Week Treatment Period	8.8 percentage of participants	15.2 percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 10 weeks

Population: Number of participants with a normal baseline and at least 1 post-baseline abnormal HbA1C value, last-observation-carried forward (LOCF) were included in the analysis.

Abnormal high HbA1c is defined as a post-baseline HbA1c \> 6.1% if baseline HbA1c ≤ 6.1% for lab samples obtained before November 17, 2010 and post-baseline HbA1c \> 6.4% if baseline HbA1c ≤ 6.4% for lab samples obtained November 17, 2010 and beyond.

Outcome measures

Outcome measures
Measure	Placebo n=210 Participants Participants received placebo by mouth, once daily for 10 weeks.	Duloxetine n=208 Participants Participants initially received 30 milligrams (mg) duloxetine by mouth, once daily for 1 week, followed by 60 mg by mouth, once daily thereafter. At end of 3 weeks, participants with a weekly mean 24-hour average pain value ≥4 in week preceding their visit had their dose escalated up to 120 mg by mouth, once daily until Week 10.
Percentage of Participants With Abnormal High Hemoglobin A1c (HbA1c) up to 10 Weeks	5.7 percentage of participants	1.0 percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 10 weeks

Population: Participants with a baseline and at least 1 post-baseline weight value, last-observation-carried forward (LOCF) were included in the analysis.

Abnormal weight gain (potentially clinically significant \[PCS\] weight gain) is defined as weight gain at last visit ≥ 7% of the baseline weight. Abnormal weight loss (PCS weight loss) is defined as weight loss at last visit ≥ 7% of the baseline weight.

Outcome measures

Outcome measures
Measure	Placebo n=256 Participants Participants received placebo by mouth, once daily for 10 weeks.	Duloxetine n=258 Participants Participants initially received 30 milligrams (mg) duloxetine by mouth, once daily for 1 week, followed by 60 mg by mouth, once daily thereafter. At end of 3 weeks, participants with a weekly mean 24-hour average pain value ≥4 in week preceding their visit had their dose escalated up to 120 mg by mouth, once daily until Week 10.
Percentage of Participants With Abnormal Weight Gain and Weight Loss up to 10 Weeks PCS Weight Gain	1.6 percentage of participants	1.2 percentage of participants
Percentage of Participants With Abnormal Weight Gain and Weight Loss up to 10 Weeks PCS Weight Loss	0.8 percentage of participants	3.1 percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 10 weeks

Population: Participants with a normal baseline and at least 1 post-baseline DBP and SBP value, last-observation-carried forward (LOCF) were included in the analysis. Participants with a normal baseline value and a nonmissing endpoint value for the variable of interest were included in the analysis.

Abnormal DPB (diastolic hypertension) is defined as sitting DBP ≥ 90 mm Hg that is also ≥ 10 mm Hg increase from baseline that is observed at last visit if highest baseline DBP \< 90 mm Hg. Abnormal SBP (systolic hypertension) is defined as sitting SBP ≥ 140 mm Hg that is also ≥ 10 mm Hg increase from baseline that is observed at last visit if highest baseline SBP \< 140 mm Hg.

Outcome measures

Outcome measures
Measure	Placebo n=202 Participants Participants received placebo by mouth, once daily for 10 weeks.	Duloxetine n=215 Participants Participants initially received 30 milligrams (mg) duloxetine by mouth, once daily for 1 week, followed by 60 mg by mouth, once daily thereafter. At end of 3 weeks, participants with a weekly mean 24-hour average pain value ≥4 in week preceding their visit had their dose escalated up to 120 mg by mouth, once daily until Week 10.
Percentage of Participants With Abnormal Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) up to 10 Weeks Diastolic Hypertension	1.0 percentage of participants	4.2 percentage of participants
Percentage of Participants With Abnormal Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) up to 10 Weeks Systolic Hypertension (N=170, 171)	4.7 percentage of participants	12.3 percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 10 weeks

Population: Participants with a normal baseline and at least 1 post-baseline pulse rate value, last-observation-carried forward (LOCF) were included in the analysis.

Abnormal pulse rate (tachycardia) is defined as a sitting heart rate (HR) ≥ 100 beats per minute (bpm) that is also ≥ 10 bpm compared to baseline, at last visit if highest baseline HR \< 100 bpm.

Outcome measures

Outcome measures
Measure	Placebo n=257 Participants Participants received placebo by mouth, once daily for 10 weeks.	Duloxetine n=264 Participants Participants initially received 30 milligrams (mg) duloxetine by mouth, once daily for 1 week, followed by 60 mg by mouth, once daily thereafter. At end of 3 weeks, participants with a weekly mean 24-hour average pain value ≥4 in week preceding their visit had their dose escalated up to 120 mg by mouth, once daily until Week 10.
Percentage of Participants With Abnormal Pulse Rate up to 10 Weeks	0.0 percentage of participants	1.1 percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 10 weeks

Population: Intent-to-treat (ITT) participants with a baseline and at least 1 post-baseline REU value, last-observation-carried forward (LOCF) were included in the analysis.

REU captures information regarding the participant's work status and/or health care utilization. Investigators gather information from medical records, psychiatric history, and direct questioning of the participant and his or her family to complete the questionnaire. Responses to each item, comparing baseline to endpoint, are characterized as "Better," "Same," or "Worse." Better: an increase in time spent working/volunteering/holding a job, decrease in number of health care visits; Same: no change in time spent working/volunteering/holding a job, no change in number of health care visits; Worse: decrease in time spent working/volunteering/holding a job, increase in number of health care visits.

Outcome measures

Outcome measures
Measure	Placebo n=260 Participants Participants received placebo by mouth, once daily for 10 weeks.	Duloxetine n=264 Participants Participants initially received 30 milligrams (mg) duloxetine by mouth, once daily for 1 week, followed by 60 mg by mouth, once daily thereafter. At end of 3 weeks, participants with a weekly mean 24-hour average pain value ≥4 in week preceding their visit had their dose escalated up to 120 mg by mouth, once daily until Week 10.
Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks Outpatient Group Visits-Better	0.4 percentage of participants	0.0 percentage of participants
Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks Outpatient Group Visits-Same	99.6 percentage of participants	100.0 percentage of participants
Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks Outpatient Group Visits-Worse	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks Outpatient Individual Visits-Better	2.4 percentage of participants	0.8 percentage of participants
Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks Outpatient Individual Visits-Same	96.7 percentage of participants	99.2 percentage of participants
Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks Outpatient Individual Visits-Worse	0.8 percentage of participants	0.0 percentage of participants
Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks ER Visits for Psychiatric Illness-Better	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks ER Visits for Psychiatric Illness-Same	100.0 percentage of participants	100.0 percentage of participants
Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks ER Visits for Psychiatric Illness-Worse	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks ER Visits for Non-psychiatric Illness-Better	5.7 percentage of participants	3.7 percentage of participants
Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks ER Visits for Non-psychiatric Illness-Same	92.7 percentage of participants	95.5 percentage of participants
Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks ER Visits for Non-psychiatric Illness-Worse	1.6 percentage of participants	0.8 percentage of participants
Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks Outpatient Visits to Other Physicians-Better	20.4 percentage of participants	26.0 percentage of participants
Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks Outpatient Visits to Other Physicians-Same	74.3 percentage of participants	69.4 percentage of participants
Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks Outpatient Visits to Other Physicians-Worse	5.3 percentage of participants	4.5 percentage of participants
Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks Average Hours Worked for Pay per Week-Better	15.2 percentage of participants	18.9 percentage of participants
Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks Average Hours Worked for Pay per Week-Same	64.3 percentage of participants	69.4 percentage of participants
Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks Average Hours Worked for Pay per Week-Worse	20.5 percentage of participants	11.7 percentage of participants
Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks How Long Participant Had This Job-Better	25.2 percentage of participants	20.2 percentage of participants
Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks How Long Participant Had This Job-Same	65.8 percentage of participants	69.7 percentage of participants
Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks How Long Participant Had This Job-Worse	9.0 percentage of participants	10.1 percentage of participants
Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks Average Hours of Volunteer Work per Week-Better	10.7 percentage of participants	11.1 percentage of participants
Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks Average Hours of Volunteer Work per Week-Same	67.9 percentage of participants	72.2 percentage of participants
Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks Average Hours of Volunteer Work per Week-Worse	21.4 percentage of participants	16.7 percentage of participants
Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks Psychiatric Visits-Better	1.6 percentage of participants	0.8 percentage of participants
Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks Psychiatric Visits-Same	98.4 percentage of participants	99.2 percentage of participants
Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks Psychiatric Visits-Worse	0.0 percentage of participants	0.0 percentage of participants

Adverse Events

Placebo

Serious events: 3 serious events

Other events: 129 other events

Deaths: 0 deaths

Duloxetine

Serious events: 5 serious events

Other events: 167 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=260 participants at risk Participants received placebo by mouth, once daily for 10 weeks.	Duloxetine n=264 participants at risk Participants initially received 30 milligrams (mg) duloxetine by mouth, once daily for 1 week, followed by 60 mg by mouth, once daily thereafter. At end of 3 weeks, participants with a weekly mean 24-hour average pain value ≥4 in week preceding their visit had their dose escalated up to 120 mg by mouth, once daily until Week 10.
Cardiac disorders Coronary artery disease	0.00% 0/260	0.38% 1/264 • Number of events 1
Gastrointestinal disorders Pancreatitis	0.38% 1/260 • Number of events 1	0.00% 0/264
Hepatobiliary disorders Cholecystitis	0.38% 1/260 • Number of events 1	0.00% 0/264
Infections and infestations Urosepsis	0.00% 0/260	0.38% 1/264 • Number of events 1
Injury, poisoning and procedural complications Fall	0.00% 0/260	0.38% 1/264 • Number of events 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.38% 1/260 • Number of events 1	0.00% 0/264
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	0.00% 0/260	0.38% 1/264 • Number of events 1
Nervous system disorders Cerebrovascular accident	0.38% 1/260 • Number of events 1	0.00% 0/264
Nervous system disorders Syncope	0.00% 0/260	0.38% 1/264 • Number of events 1

Other adverse events

Other adverse events
Measure	Placebo n=260 participants at risk Participants received placebo by mouth, once daily for 10 weeks.	Duloxetine n=264 participants at risk Participants initially received 30 milligrams (mg) duloxetine by mouth, once daily for 1 week, followed by 60 mg by mouth, once daily thereafter. At end of 3 weeks, participants with a weekly mean 24-hour average pain value ≥4 in week preceding their visit had their dose escalated up to 120 mg by mouth, once daily until Week 10.
Cardiac disorders Palpitations	0.77% 2/260 • Number of events 2	1.5% 4/264 • Number of events 4
Eye disorders Vision blurred	0.38% 1/260 • Number of events 1	1.9% 5/264 • Number of events 5
Gastrointestinal disorders Abdominal discomfort	0.00% 0/260	1.9% 5/264 • Number of events 6
Gastrointestinal disorders Abdominal pain	0.77% 2/260 • Number of events 2	1.5% 4/264 • Number of events 4
Gastrointestinal disorders Abdominal pain upper	0.38% 1/260 • Number of events 1	2.7% 7/264 • Number of events 7
Gastrointestinal disorders Constipation	3.1% 8/260 • Number of events 8	8.7% 23/264 • Number of events 24
Gastrointestinal disorders Diarrhoea	3.8% 10/260 • Number of events 11	6.8% 18/264 • Number of events 19
Gastrointestinal disorders Dry mouth	2.7% 7/260 • Number of events 7	9.5% 25/264 • Number of events 25
Gastrointestinal disorders Dyspepsia	0.38% 1/260 • Number of events 1	1.1% 3/264 • Number of events 3
Gastrointestinal disorders Flatulence	0.38% 1/260 • Number of events 1	2.3% 6/264 • Number of events 6
Gastrointestinal disorders Nausea	4.6% 12/260 • Number of events 12	15.5% 41/264 • Number of events 43
Gastrointestinal disorders Vomiting	1.2% 3/260 • Number of events 3	4.2% 11/264 • Number of events 12
General disorders Fatigue	1.5% 4/260 • Number of events 4	6.8% 18/264 • Number of events 19
General disorders Feeling jittery	0.38% 1/260 • Number of events 1	1.1% 3/264 • Number of events 3
General disorders Oedema peripheral	1.2% 3/260 • Number of events 4	1.1% 3/264 • Number of events 3
General disorders Therapeutic response unexpected	1.5% 4/260 • Number of events 5	1.1% 3/264 • Number of events 4
General disorders Thirst	0.00% 0/260	1.1% 3/264 • Number of events 3
Infections and infestations Bronchitis	1.5% 4/260 • Number of events 4	0.38% 1/264 • Number of events 1
Infections and infestations Gastroenteritis viral	1.2% 3/260 • Number of events 3	0.00% 0/264
Infections and infestations Nasopharyngitis	3.1% 8/260 • Number of events 8	1.5% 4/264 • Number of events 4
Infections and infestations Upper respiratory tract infection	1.2% 3/260 • Number of events 3	0.76% 2/264 • Number of events 2
Infections and infestations Urinary tract infection	1.2% 3/260 • Number of events 3	0.38% 1/264 • Number of events 1
Investigations Alanine aminotransferase increased	1.5% 4/260 • Number of events 4	0.76% 2/264 • Number of events 2
Investigations Aspartate aminotransferase increased	1.5% 4/260 • Number of events 4	0.76% 2/264 • Number of events 2
Investigations Liver function test abnormal	0.00% 0/260	1.1% 3/264 • Number of events 3
Investigations Weight increased	0.38% 1/260 • Number of events 1	1.1% 3/264 • Number of events 3
Metabolism and nutrition disorders Decreased appetite	0.38% 1/260 • Number of events 1	5.7% 15/264 • Number of events 15
Musculoskeletal and connective tissue disorders Arthralgia	1.5% 4/260 • Number of events 4	2.3% 6/264 • Number of events 7
Musculoskeletal and connective tissue disorders Back pain	1.5% 4/260 • Number of events 4	0.76% 2/264 • Number of events 2
Musculoskeletal and connective tissue disorders Muscle spasms	1.2% 3/260 • Number of events 3	0.38% 1/264 • Number of events 1
Musculoskeletal and connective tissue disorders Myalgia	1.2% 3/260 • Number of events 3	0.00% 0/264
Musculoskeletal and connective tissue disorders Pain in extremity	1.5% 4/260 • Number of events 4	1.1% 3/264 • Number of events 4
Nervous system disorders Dizziness	2.7% 7/260 • Number of events 7	6.4% 17/264 • Number of events 17
Nervous system disorders Dysgeusia	0.38% 1/260 • Number of events 1	1.5% 4/264 • Number of events 4
Nervous system disorders Headache	3.8% 10/260 • Number of events 10	6.1% 16/264 • Number of events 21
Nervous system disorders Somnolence	2.7% 7/260 • Number of events 7	5.3% 14/264 • Number of events 14
Nervous system disorders Tremor	0.38% 1/260 • Number of events 1	1.1% 3/264 • Number of events 3
Psychiatric disorders Abnormal dreams	1.9% 5/260 • Number of events 5	0.76% 2/264 • Number of events 2
Psychiatric disorders Anxiety	1.9% 5/260 • Number of events 5	1.5% 4/264 • Number of events 4
Psychiatric disorders Insomnia	1.2% 3/260 • Number of events 3	4.9% 13/264 • Number of events 15
Psychiatric disorders Libido decreased	0.38% 1/260 • Number of events 1	1.9% 5/264 • Number of events 5
Renal and urinary disorders Dysuria	0.00% 0/260	1.1% 3/264 • Number of events 3
Renal and urinary disorders Pollakiuria	0.00% 0/260	2.3% 6/264 • Number of events 6
Renal and urinary disorders Urine flow decreased	0.00% 0/260	1.1% 3/264 • Number of events 3
Reproductive system and breast disorders Erectile dysfunction	0.38% 1/260 • Number of events 1	1.9% 5/264 • Number of events 5
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/260	2.3% 6/264 • Number of events 6
Skin and subcutaneous tissue disorders Dermatitis contact	0.38% 1/260 • Number of events 1	1.1% 3/264 • Number of events 3
Skin and subcutaneous tissue disorders Hyperhidrosis	0.38% 1/260 • Number of events 1	3.8% 10/264 • Number of events 10
Skin and subcutaneous tissue disorders Night sweats	0.00% 0/260	1.5% 4/264 • Number of events 4
Skin and subcutaneous tissue disorders Rash	0.77% 2/260 • Number of events 2	1.1% 3/264 • Number of events 3
Vascular disorders Hot flush	0.00% 0/260	1.5% 4/264 • Number of events 4
Vascular disorders Hypertension	0.77% 2/260 • Number of events 2	1.1% 3/264 • Number of events 3

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60