Trial Outcomes & Findings for A Study in Depression and Associated Painful Physical Symptoms (NCT NCT01070329)

Last Updated: 2012-02-13

Results Overview

A 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). The overall change is based on the estimated main treatment effect. The Least Squares (LS) Mean Value was adjusted for treatment, investigator, visit, baseline, treatment\*visit interaction, and baseline\*visit interaction.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

527 participants

Primary outcome timeframe

Day 1 through 8 weeks

Results posted on

2012-02-13

Participant Flow

Double-blind treatment phase: Participants randomly assigned to duloxetine received 30 mg once daily (QD) for 1 week, followed by 60 mg QD for 7 weeks. Participants randomly assigned to placebo received placebo QD for 8 weeks. Taper phase: Duloxetine group: 30 mg QD for 2 weeks. Placebo group: QD for 2 weeks.

Participant milestones

Participant milestones
Measure	Duloxetine Participants received 30 milligrams (mg) of duloxetine once daily (QD) by mouth (po) for 1 week, followed by 60 mg QD, po for 7 weeks. Participants were given the option to take duloxetine 30 mg QD, po for a 2-week taper phase.	Placebo Participants received placebo QD, po for 8 weeks.
Overall Study STARTED	261	266
Overall Study COMPLETED	209	217
Overall Study NOT COMPLETED	52	49

Reasons for withdrawal

Reasons for withdrawal
Measure	Duloxetine Participants received 30 milligrams (mg) of duloxetine once daily (QD) by mouth (po) for 1 week, followed by 60 mg QD, po for 7 weeks. Participants were given the option to take duloxetine 30 mg QD, po for a 2-week taper phase.	Placebo Participants received placebo QD, po for 8 weeks.
Overall Study Adverse Event	13	10
Overall Study Lost to Follow-up	22	12
Overall Study Withdrawal by Subject	9	11
Overall Study Protocol Violation	3	8
Overall Study Lack of Efficacy	2	6
Overall Study Physician Decision	2	1
Overall Study Entry Criteria Not Met	1	0
Overall Study Sponsor Decision	0	1

Baseline Characteristics

A Study in Depression and Associated Painful Physical Symptoms

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Duloxetine n=261 Participants Participants received 30 milligrams (mg) of duloxetine once daily (QD) by mouth (po) for 1 week, followed by 60 mg QD, po for 7 weeks. Participants were given the option to take duloxetine 30 mg QD, po for a 2-week taper phase.	Placebo n=266 Participants Participants received placebo QD, po for 8 weeks.	Total n=527 Participants Total of all reporting groups
Age Continuous	45.15 years STANDARD_DEVIATION 12.47 • n=93 Participants	44.21 years STANDARD_DEVIATION 12.38 • n=4 Participants	44.68 years STANDARD_DEVIATION 12.42 • n=27 Participants
Sex: Female, Male Female	183 Participants n=93 Participants	178 Participants n=4 Participants	361 Participants n=27 Participants
Sex: Female, Male Male	78 Participants n=93 Participants	88 Participants n=4 Participants	166 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	38 Participants n=93 Participants	32 Participants n=4 Participants	70 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	223 Participants n=93 Participants	234 Participants n=4 Participants	457 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	4 Participants n=93 Participants	2 Participants n=4 Participants	6 Participants n=27 Participants
Race (NIH/OMB) Asian	4 Participants n=93 Participants	5 Participants n=4 Participants	9 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=93 Participants	0 Participants n=4 Participants	2 Participants n=27 Participants
Race (NIH/OMB) Black or African American	64 Participants n=93 Participants	66 Participants n=4 Participants	130 Participants n=27 Participants
Race (NIH/OMB) White	184 Participants n=93 Participants	190 Participants n=4 Participants	374 Participants n=27 Participants
Race (NIH/OMB) More than one race	3 Participants n=93 Participants	3 Participants n=4 Participants	6 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Region of Enrollment United States	242 participants n=93 Participants	248 participants n=4 Participants	490 participants n=27 Participants
Region of Enrollment Puerto Rico	19 participants n=93 Participants	18 participants n=4 Participants	37 participants n=27 Participants
Brief Pain Inventory Severity: Worst Pain Score (BPI-S: Worst Pain)	7.06 units on a scale STANDARD_DEVIATION 1.67 • n=93 Participants	6.88 units on a scale STANDARD_DEVIATION 1.67 • n=4 Participants	6.97 units on a scale STANDARD_DEVIATION 1.67 • n=27 Participants
Brief Pain Inventory Severity: Least Pain Score (BPI-S: Least Pain)	4.25 units on a scale STANDARD_DEVIATION 1.99 • n=93 Participants	4.11 units on a scale STANDARD_DEVIATION 1.97 • n=4 Participants	4.18 units on a scale STANDARD_DEVIATION 1.98 • n=27 Participants
Brief Pain Inventory Severity: Average Pain Score (BPI-S: Average Pain)	5.78 units on a scale STANDARD_DEVIATION 1.64 • n=93 Participants	5.63 units on a scale STANDARD_DEVIATION 1.69 • n=4 Participants	5.70 units on a scale STANDARD_DEVIATION 1.66 • n=27 Participants
Brief Pain Inventory Severity: Pain Right Now Score (BPI-S: Pain Right Now)	5.41 units on a scale STANDARD_DEVIATION 2.13 • n=93 Participants	5.26 units on a scale STANDARD_DEVIATION 2.18 • n=4 Participants	5.34 units on a scale STANDARD_DEVIATION 2.16 • n=27 Participants
Brief Pain Inventory - Interference (BPI-I)	6.04 units on a scale STANDARD_DEVIATION 2.03 • n=93 Participants	5.98 units on a scale STANDARD_DEVIATION 1.97 • n=4 Participants	6.01 units on a scale STANDARD_DEVIATION 2.00 • n=27 Participants
Clinical Global Impressions of Severity Scale (CGI-S)	4.39 units on a scale STANDARD_DEVIATION 0.56 • n=93 Participants	4.38 units on a scale STANDARD_DEVIATION 0.53 • n=4 Participants	4.39 units on a scale STANDARD_DEVIATION 0.54 • n=27 Participants
Montgomery-Asberg Depression Rating Scale (MADRS) Total Score	30.06 units on a scale STANDARD_DEVIATION 4.72 • n=93 Participants	29.84 units on a scale STANDARD_DEVIATION 4.82 • n=4 Participants	29.95 units on a scale STANDARD_DEVIATION 4.76 • n=27 Participants
Sheehan Disability Scale-Item 1 (SDS-Item 1), N=187, 193, 380	5.97 units on a scale STANDARD_DEVIATION 2.06 • n=93 Participants	6.22 units on a scale STANDARD_DEVIATION 2.04 • n=4 Participants	6.10 units on a scale STANDARD_DEVIATION 2.05 • n=27 Participants
Sheehan Disability Scale-Item 2 (SDS-Item 2)	6.51 units on a scale STANDARD_DEVIATION 2.20 • n=93 Participants	6.30 units on a scale STANDARD_DEVIATION 2.11 • n=4 Participants	6.40 units on a scale STANDARD_DEVIATION 2.16 • n=27 Participants
Sheehan Disability Scale-Item 3 (SDS-Item 3)	6.41 units on a scale STANDARD_DEVIATION 2.17 • n=93 Participants	6.31 units on a scale STANDARD_DEVIATION 2.05 • n=4 Participants	6.36 units on a scale STANDARD_DEVIATION 2.11 • n=27 Participants
Sheehan Disability Scale -Total Score (SDS Total)	19.16 units on a scale STANDARD_DEVIATION 6.02 • n=93 Participants	18.88 units on a scale STANDARD_DEVIATION 5.70 • n=4 Participants	19.02 units on a scale STANDARD_DEVIATION 5.86 • n=27 Participants
Number of Previous Major Depressive Disorder (MDD) Episodes	3.58 number of previous episodes STANDARD_DEVIATION 3.34 • n=93 Participants	3.65 number of previous episodes STANDARD_DEVIATION 3.42 • n=4 Participants	3.61 number of previous episodes STANDARD_DEVIATION 3.38 • n=27 Participants

PRIMARY outcome

Timeframe: Day 1 through 8 weeks

Population: All randomized participants with a baseline and at least 1 post-baseline result.

Outcome measures

Outcome measures
Measure	Duloxetine n=255 Participants Participants received 30 milligrams (mg) of duloxetine once daily (QD) by mouth (po) for 1 week, followed by 60 mg QD, po for 7 weeks. Participants were given the option to take duloxetine 30 mg QD, po for a 2-week taper phase.	Placebo n=265 Participants Participants received placebo QD, po for 8 weeks.
Change From Baseline in the Brief Pain Inventory-Short Form (BPI-SF) Average Pain Score During the 8-Week Treatment Period	-1.66 units on a scale Standard Error 0.10	-1.17 units on a scale Standard Error 0.10

PRIMARY outcome

Timeframe: Baseline, 8 weeks

Population: All randomized participants with a baseline and at least 1 post-baseline result.

The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). The Least Squares (LS) Mean Value was adjusted for treatment, investigator, visit, baseline, treatment\*visit interaction, and baseline\*visit interaction.

Outcome measures

Outcome measures
Measure	Duloxetine n=255 Participants Participants received 30 milligrams (mg) of duloxetine once daily (QD) by mouth (po) for 1 week, followed by 60 mg QD, po for 7 weeks. Participants were given the option to take duloxetine 30 mg QD, po for a 2-week taper phase.	Placebo n=265 Participants Participants received placebo QD, po for 8 weeks.
Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Week 8	-14.96 units on a scale Standard Error 0.58	-10.77 units on a scale Standard Error 0.57

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: All randomized participants with a baseline and at least 1 post-baseline result.

SDS is completed by participant; used to assess effect of the participant's symptoms on their work/social/family life. Total scores range from 0 to 30; higher values indicate greater disruption in the participant's work/social/family life. Each item score ranges from 0 to 10 with higher values indicating greater disruption in the participant's work/school life (item 1), social life/leisure activities (item 2), or family life/home responsibilities (item 3). The LS Mean Value was adjusted for treatment, investigator, visit, baseline, treatment\*visit interaction, and baseline\*visit interaction.

Outcome measures

Outcome measures
Measure	Duloxetine n=255 Participants Participants received 30 milligrams (mg) of duloxetine once daily (QD) by mouth (po) for 1 week, followed by 60 mg QD, po for 7 weeks. Participants were given the option to take duloxetine 30 mg QD, po for a 2-week taper phase.	Placebo n=265 Participants Participants received placebo QD, po for 8 weeks.
Change From Baseline in the Sheehan Disability Scale (SDS) Total and Item Scores at Week 8 Disrupt Work/School Work (N=178, 188)	-3.01 units on a scale Standard Error 0.19	-2.06 units on a scale Standard Error 0.19
Change From Baseline in the Sheehan Disability Scale (SDS) Total and Item Scores at Week 8 Disrupt Social Life/Leisure Activities	-3.14 units on a scale Standard Error 0.17	-2.17 units on a scale Standard Error 0.16
Change From Baseline in the Sheehan Disability Scale (SDS) Total and Item Scores at Week 8 SDS Total Score	-9.16 units on a scale Standard Error 0.47	-6.28 units on a scale Standard Error 0.46
Change From Baseline in the Sheehan Disability Scale (SDS) Total and Item Scores at Week 8 Disrupt Family/Home Responsibilities	-3.04 units on a scale Standard Error 0.17	-2.09 units on a scale Standard Error 0.17

SECONDARY outcome

Timeframe: Baseline, up to 8 weeks

Population: All randomized participants with a baseline and at least 1 post-baseline result, Last Observation Carried Forward (LOCF).

The Montgomery-Asberg Depression Rating Scale (MADRS) is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). Remission is defined as achieving a MADRS total score ≤12.

Outcome measures

Outcome measures
Measure	Duloxetine n=255 Participants Participants received 30 milligrams (mg) of duloxetine once daily (QD) by mouth (po) for 1 week, followed by 60 mg QD, po for 7 weeks. Participants were given the option to take duloxetine 30 mg QD, po for a 2-week taper phase.	Placebo n=265 Participants Participants received placebo QD, po for 8 weeks.
Change From Baseline in the Percentage of Participants Achieving Remission up to Week 8	37.3 percentage of participants	23.0 percentage of participants

SECONDARY outcome

Timeframe: Up to 8 weeks

Population: All randomized participants with a baseline and at least 1 post-baseline value.

The Montgomery-Asberg Depression Rating Scale (MADRS) is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist. Items are rated on a scale from 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). Remission is defined as achieving a MADRS total score ≤12 at the last 2 nonmissing visits (for example, visit 3 \[week 1\] and visit 4 \[week 2\], or visit 4 \[week 2\] and visit 5 \[week 4\], or visit 5 \[week 4\] and visit 6 \[week 8\]).

Outcome measures

Outcome measures
Measure	Duloxetine n=255 Participants Participants received 30 milligrams (mg) of duloxetine once daily (QD) by mouth (po) for 1 week, followed by 60 mg QD, po for 7 weeks. Participants were given the option to take duloxetine 30 mg QD, po for a 2-week taper phase.	Placebo n=265 Participants Participants received placebo QD, po for 8 weeks.
Percentage of Participants Achieving Remission up to Week 8	15.7 percentage of participants	11.7 percentage of participants

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: All randomized participants with a baseline and at least 1 post-baseline result.

The MADRS is a rating scale for severity of depressive mood and symptoms. The MADRS has a 10-item checklist. Items are rated on a scale from 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). The Least Squares (LS) Mean Value was adjusted for treatment, investigator, visit, baseline, treatment\*visit interaction, and baseline\*visit interaction.

Outcome measures

Outcome measures
Measure	Duloxetine n=255 Participants Participants received 30 milligrams (mg) of duloxetine once daily (QD) by mouth (po) for 1 week, followed by 60 mg QD, po for 7 weeks. Participants were given the option to take duloxetine 30 mg QD, po for a 2-week taper phase.	Placebo n=265 Participants Participants received placebo QD, po for 8 weeks.
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Week 4	-11.48 units on a scale Standard Error 0.49	-8.67 units on a scale Standard Error 0.48

SECONDARY outcome

Timeframe: Baseline, 2 weeks

Population: All randomized participants with a baseline and at least 1 post-baseline result.

The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range from 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). The Least Squares (LS) Mean Value was adjusted for treatment, investigator, visit, baseline, treatment\*visit interaction, and baseline\*visit interaction.

Outcome measures

Outcome measures
Measure	Duloxetine n=255 Participants Participants received 30 milligrams (mg) of duloxetine once daily (QD) by mouth (po) for 1 week, followed by 60 mg QD, po for 7 weeks. Participants were given the option to take duloxetine 30 mg QD, po for a 2-week taper phase.	Placebo n=265 Participants Participants received placebo QD, po for 8 weeks.
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Week 2	-8.60 units on a scale Standard Error 0.41	-6.52 units on a scale Standard Error 0.40

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: All randomized participants with a baseline and at least 1 post-baseline result.

Measures pain severity and interference on 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. Average interference=average of nonmissing scores of individual interference items. LS Mean Value adjusted for treatment, investigator, visit, baseline, treatment\*visit interaction, and baseline\*visit interaction.

Outcome measures

Outcome measures
Measure	Duloxetine n=255 Participants Participants received 30 milligrams (mg) of duloxetine once daily (QD) by mouth (po) for 1 week, followed by 60 mg QD, po for 7 weeks. Participants were given the option to take duloxetine 30 mg QD, po for a 2-week taper phase.	Placebo n=265 Participants Participants received placebo QD, po for 8 weeks.
Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 8 BPI Severity for Worst Pain	-1.88 units on a scale Standard Error 0.11	-1.32 units on a scale Standard Error 0.11
Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 8 BPI Severity for Pain Right Now	-1.82 units on a scale Standard Error 0.11	-1.25 units on a scale Standard Error 0.11
Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 8 BPI Pain Interference with General Activity	-1.87 units on a scale Standard Error 0.12	-1.44 units on a scale Standard Error 0.12
Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 8 BPI Pain Interference with Mood	-2.25 units on a scale Standard Error 0.12	-1.77 units on a scale Standard Error 0.12
Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 8 BPI Pain Interference with Walking Ability	-1.62 units on a scale Standard Error 0.11	-1.20 units on a scale Standard Error 0.11
Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 8 BPI Pain Interference with Normal Work	-1.88 units on a scale Standard Error 0.12	-1.47 units on a scale Standard Error 0.12
Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 8 BPI Pain Interference with Relations With Others	-1.90 units on a scale Standard Error 0.13	-1.53 units on a scale Standard Error 0.12
Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 8 BPI Severity for Least Pain	-1.18 units on a scale Standard Error 0.10	-0.80 units on a scale Standard Error 0.10
Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 8 BPI Severity for Average Pain	-1.66 units on a scale Standard Error 0.10	-1.17 units on a scale Standard Error 0.10
Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 8 BPI Pain Interference with Sleep	-2.13 units on a scale Standard Error 0.14	-1.74 units on a scale Standard Error 0.14
Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 8 BPI Pain Interference with Enjoyment of Life	-2.32 units on a scale Standard Error 0.13	-1.84 units on a scale Standard Error 0.13
Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 8 BPI Mean Pain Interference Score	-2.03 units on a scale Standard Error 0.11	-1.58 units on a scale Standard Error 0.11

SECONDARY outcome

Timeframe: 8 weeks

Population: All randomized participants with a baseline and at least 1 post-baseline result.

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 (LS) Mean Value was adjusted for treatment, investigator, visit, and treatment\*visit interaction.

Outcome measures

Outcome measures
Measure	Duloxetine n=255 Participants Participants received 30 milligrams (mg) of duloxetine once daily (QD) by mouth (po) for 1 week, followed by 60 mg QD, po for 7 weeks. Participants were given the option to take duloxetine 30 mg QD, po for a 2-week taper phase.	Placebo n=265 Participants Participants received placebo QD, po for 8 weeks.
Patient Global Impression of Improvement (PGI-I) Score at Week 8	2.48 units on a scale Standard Error 0.08	3.17 units on a scale Standard Error 0.07

SECONDARY outcome

Timeframe: Baseline through 8 weeks

Population: All randomized participants with a baseline and at least 1 post-baseline C-SSRS result.

The C-SSRS captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Number of participants with suicidal behaviors, ideations, and acts are provided. Suicidal behavior: a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, and completed suicide. Suicidal ideation: a "yes" answer to any 1 of 5 suicidal ideation questions, which includes wish to be dead, and 4 different categories of active suicidal ideation. Suicidal acts: a "yes" answer to actual attempt or completed suicide.

Outcome measures

Outcome measures
Measure	Duloxetine n=255 Participants Participants received 30 milligrams (mg) of duloxetine once daily (QD) by mouth (po) for 1 week, followed by 60 mg QD, po for 7 weeks. Participants were given the option to take duloxetine 30 mg QD, po for a 2-week taper phase.	Placebo n=265 Participants Participants received placebo QD, po for 8 weeks.
Number of Participants With Suicidal Behaviors, Ideations, and Acts Based on the Columbia Suicide Severity Rating Scale (C-SSRS) During the Double-Blind Treatment Phase Suicidal Acts	0 participants	0 participants
Number of Participants With Suicidal Behaviors, Ideations, and Acts Based on the Columbia Suicide Severity Rating Scale (C-SSRS) During the Double-Blind Treatment Phase Suicidal Behavior	2 participants	0 participants
Number of Participants With Suicidal Behaviors, Ideations, and Acts Based on the Columbia Suicide Severity Rating Scale (C-SSRS) During the Double-Blind Treatment Phase Suicidal Ideation	21 participants	34 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, up to week 8

Population: Primary analysis: All randomized participants with a baseline and at least 1 post-baseline result. Secondary analysis: Intent-to-treat (ITT) population with nonmissing baseline value and at least 1 nonmissing post-baseline value, Last Observation Carried Forward (LOCF).

The change from baseline in pulse rate at week 8 is the primary analysis. For the primary analysis of pulse rate, the Least Squares (LS) Mean Value was adjusted for treatment, investigator, baseline, treatment\*visit interaction, and baseline\*visit interaction. The change from baseline in pulse rate up to week 8 is the secondary analysis. The LS Mean Value was adjusted for treatment, investigator, and baseline.

Outcome measures

Outcome measures
Measure	Duloxetine n=255 Participants Participants received 30 milligrams (mg) of duloxetine once daily (QD) by mouth (po) for 1 week, followed by 60 mg QD, po for 7 weeks. Participants were given the option to take duloxetine 30 mg QD, po for a 2-week taper phase.	Placebo n=265 Participants Participants received placebo QD, po for 8 weeks.
Change From Baseline in Pulse Rate up to Week 8 Change from Baseline in Pulse Rate at Week 8	2.08 beats per minute (bpm) Standard Error 0.62	0.40 beats per minute (bpm) Standard Error 0.60
Change From Baseline in Pulse Rate up to Week 8 Change from Baseline in Pulse Rate up to Week 8	2.01 beats per minute (bpm) Standard Error 0.57	0.62 beats per minute (bpm) Standard Error 0.57

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, up to week 8

The change from baseline in SBP and DBP at week 8 is the primary analysis. For the primary analysis of SBP and DBP, the Least Squares (LS) Mean Value was adjusted for treatment, investigator, baseline, treatment\*visit interaction, and baseline\*visit interaction. The change from baseline in SBP and DBP up to week 8 is the secondary analysis. The LS Mean Value was adjusted for treatment, investigator, and baseline.

Outcome measures

Outcome measures
Measure	Duloxetine n=255 Participants Participants received 30 milligrams (mg) of duloxetine once daily (QD) by mouth (po) for 1 week, followed by 60 mg QD, po for 7 weeks. Participants were given the option to take duloxetine 30 mg QD, po for a 2-week taper phase.	Placebo n=265 Participants Participants received placebo QD, po for 8 weeks.
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Up to Week 8 Change from Baseline in SBP at Week 8	0.82 mm Hg Standard Error 0.71	-1.09 mm Hg Standard Error 0.70
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Up to Week 8 Change from Baseline in DBP at Week 8	1.88 mm Hg Standard Error 0.48	0.08 mm Hg Standard Error 0.47
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Up to Week 8 Change from Baseline in SBP up to Week 8	0.56 mm Hg Standard Error 0.68	-1.14 mm Hg Standard Error 0.67
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Up to Week 8 Change from Baseline in DBP up to Week 8	1.86 mm Hg Standard Error 0.46	0.05 mm Hg Standard Error 0.45

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, up to week 8

Population: Primary analysis: All randomized participants with a baseline and at least 1 post-baseline result. Secondary analysis: All randomized participants with a baseline and at least 1 nonmissing post-baseline result, Last Observation Carried Forward (LOCF).

The change from baseline in weight at week 8 is the primary analysis. For the primary analysis of weight, the Least Squares (LS) Mean Value was adjusted for treatment, investigator, baseline, treatment\*visit interaction, and baseline\*visit interaction. The change from baseline in weight up to week 8 is the secondary analysis. The LS Mean Value was adjusted for treatment, investigator, and baseline.

Outcome measures

Outcome measures
Measure	Duloxetine n=255 Participants Participants received 30 milligrams (mg) of duloxetine once daily (QD) by mouth (po) for 1 week, followed by 60 mg QD, po for 7 weeks. Participants were given the option to take duloxetine 30 mg QD, po for a 2-week taper phase.	Placebo n=265 Participants Participants received placebo QD, po for 8 weeks.
Change From Baseline in Weight up to Week 8 Change from Baseline in Weight at Week 8	-0.69 kilograms (kg) Standard Error 0.14	-0.15 kilograms (kg) Standard Error 0.14
Change From Baseline in Weight up to Week 8 Change from Baseline in Weight up to Week 8	-0.66 kilograms (kg) Standard Error 0.14	-0.09 kilograms (kg) Standard Error 0.13

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline through 8 weeks

Population: All randomized participants with a normal baseline (respective to the specified direction) and at least 1 post-baseline result.

Laboratory assessment of creatinine during the double-blind treatment phase. Normal creatinine ranges for males are 40.00 micromoles per liter (µmol/L) (low) to 110.00 µmol/L (high). Normal creatinine ranges for females are 31.00 µmol/L (low) to 101.00 µmol/L (high).

Outcome measures

Outcome measures
Measure	Duloxetine n=215 Participants Participants received 30 milligrams (mg) of duloxetine once daily (QD) by mouth (po) for 1 week, followed by 60 mg QD, po for 7 weeks. Participants were given the option to take duloxetine 30 mg QD, po for a 2-week taper phase.	Placebo n=229 Participants Participants received placebo QD, po for 8 weeks.
Number of Participants With Abnormal Laboratory Values During the Double-Blind Treatment Phase - High Creatinine	1 participants	9 participants

Adverse Events

Duloxetine

Serious events: 1 serious events

Other events: 170 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 135 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Duloxetine n=261 participants at risk Participants received 30 milligrams (mg) of duloxetine once daily (QD) by mouth (po) for 1 week, followed by 60 mg QD, po for 7 weeks. Participants were given the option to take duloxetine 30 mg QD, po for a 2-week taper phase.	Placebo n=266 participants at risk Participants received placebo QD, po for 8 weeks.
General disorders Non-cardiac chest pain	0.38% 1/261 • Number of events 1	0.00% 0/266
Infections and infestations Gangrene	0.00% 0/261	0.38% 1/266 • Number of events 1
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/261	0.38% 1/266 • Number of events 1
Psychiatric disorders Suicidal ideation	0.00% 0/261	0.38% 1/266 • Number of events 1

Other adverse events

Other adverse events
Measure	Duloxetine n=261 participants at risk Participants received 30 milligrams (mg) of duloxetine once daily (QD) by mouth (po) for 1 week, followed by 60 mg QD, po for 7 weeks. Participants were given the option to take duloxetine 30 mg QD, po for a 2-week taper phase.	Placebo n=266 participants at risk Participants received placebo QD, po for 8 weeks.
Gastrointestinal disorders Constipation	4.6% 12/261 • Number of events 12	4.1% 11/266 • Number of events 11
Gastrointestinal disorders Diarrhoea	6.9% 18/261 • Number of events 18	2.6% 7/266 • Number of events 7
Gastrointestinal disorders Dry mouth	11.5% 30/261 • Number of events 30	8.3% 22/266 • Number of events 22
Gastrointestinal disorders Dyspepsia	2.7% 7/261 • Number of events 7	3.0% 8/266 • Number of events 8
Gastrointestinal disorders Nausea	17.6% 46/261 • Number of events 48	8.3% 22/266 • Number of events 22
General disorders Fatigue	2.7% 7/261 • Number of events 7	1.9% 5/266 • Number of events 5
Infections and infestations Nasopharyngitis	1.1% 3/261 • Number of events 3	2.3% 6/266 • Number of events 6
Metabolism and nutrition disorders Decreased appetite	3.8% 10/261 • Number of events 11	0.75% 2/266 • Number of events 2
Nervous system disorders Dizziness	6.5% 17/261 • Number of events 18	4.5% 12/266 • Number of events 13
Nervous system disorders Headache	8.8% 23/261 • Number of events 25	9.0% 24/266 • Number of events 25
Nervous system disorders Somnolence	8.4% 22/261 • Number of events 22	3.4% 9/266 • Number of events 9
Psychiatric disorders Depression	0.00% 0/261	2.3% 6/266 • Number of events 6
Psychiatric disorders Insomnia	5.4% 14/261 • Number of events 16	2.6% 7/266 • Number of events 7
Skin and subcutaneous tissue disorders Hyperhidrosis	3.1% 8/261 • Number of events 8	0.00% 0/266

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