Trial Outcomes & Findings for A Study Comparing Duloxetine and Placebo in the Treatment of Fibromyalgia (NCT NCT00673452)

NCT ID: NCT00673452

Last Updated: 2010-06-24

Results Overview

The PGI-Improvement scale is a patient-rated instrument that measures perceived improvement in symptoms. It is a 7-point scale where a score of 1 indicates that the patient is "very much improved," a score of 4 indicates that the patient has experienced "no change," and a score of 7 indicates that the patient is "very much worse."

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 530 participants
• Primary outcome timeframe: 12 weeks
• Results posted on: 2010-06-24

Participant Flow

All patients were on duloxetine in the continuation phase. The continuation phase was for exploratory purpose only, and the results will not be presented further.

Participant milestones

Measure	Duloxetine 60-120 mg, oral, daily, 12 weeks	Placebo oral, daily, 12 weeks
Acute Double-Blind Phase STARTED	263	267
Acute Double-Blind Phase COMPLETED	176	187
Acute Double-Blind Phase NOT COMPLETED	87	80
Continuation Double-Blind Phase STARTED	176	187
Continuation Double-Blind Phase COMPLETED	151	153
Continuation Double-Blind Phase NOT COMPLETED	25	34

Reasons for withdrawal

Measure	Duloxetine 60-120 mg, oral, daily, 12 weeks	Placebo oral, daily, 12 weeks
Acute Double-Blind Phase Adverse Event	41	24
Acute Double-Blind Phase Lack of Efficacy	9	14
Acute Double-Blind Phase Lost to Follow-up	16	19
Acute Double-Blind Phase Physician Decision	0	6
Acute Double-Blind Phase Protocol Violation	5	3
Acute Double-Blind Phase Sponsor Decision	0	1
Acute Double-Blind Phase Withdrawal by Subject	16	13
Continuation Double-Blind Phase Adverse Event	5	13
Continuation Double-Blind Phase Withdrawal by Subject	9	5
Continuation Double-Blind Phase Lost to Follow-up	4	5
Continuation Double-Blind Phase Lack of Efficacy	2	5
Continuation Double-Blind Phase Protocol Violation	2	3
Continuation Double-Blind Phase Sponsor Decision	0	3
Continuation Double-Blind Phase Physician Decision	2	0
Continuation Double-Blind Phase Death - Cervical vertebral fracture	1	0

Baseline Characteristics

A Study Comparing Duloxetine and Placebo in the Treatment of Fibromyalgia

Baseline characteristics by cohort

Measure	Duloxetine n=263 Participants 60-120 mg, oral, daily, 12 weeks	Placebo n=267 Participants oral, daily, 12 weeks	Total n=530 Participants Total of all reporting groups
Age Continuous	50.74 years STANDARD_DEVIATION 11.26 • n=5 Participants	49.62 years STANDARD_DEVIATION 10.84 • n=7 Participants	50.18 years STANDARD_DEVIATION 11.05 • n=5 Participants
Sex: Female, Male Female	244 Participants n=5 Participants	250 Participants n=7 Participants	494 Participants n=5 Participants
Sex: Female, Male Male	19 Participants n=5 Participants	17 Participants n=7 Participants	36 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	204 participants n=5 Participants	206 participants n=7 Participants	410 participants n=5 Participants
Race/Ethnicity, Customized Hispanic	37 participants n=5 Participants	46 participants n=7 Participants	83 participants n=5 Participants
Race/Ethnicity, Customized Other - Not Specified	22 participants n=5 Participants	15 participants n=7 Participants	37 participants n=5 Participants
Region of Enrollment United States	263 participants n=5 Participants	267 participants n=7 Participants	530 participants n=5 Participants
Alcohol Consumption Yes	89 participants n=5 Participants	90 participants n=7 Participants	179 participants n=5 Participants
Alcohol Consumption No	174 participants n=5 Participants	177 participants n=7 Participants	351 participants n=5 Participants
Generalized Anxiety Disorder (GAD) Status Yes	19 participants n=5 Participants	24 participants n=7 Participants	43 participants n=5 Participants
Generalized Anxiety Disorder (GAD) Status No	244 participants n=5 Participants	243 participants n=7 Participants	487 participants n=5 Participants
Major Depressive Disorder (MDD) Status Yes	44 participants n=5 Participants	53 participants n=7 Participants	97 participants n=5 Participants
Major Depressive Disorder (MDD) Status No	219 participants n=5 Participants	214 participants n=7 Participants	433 participants n=5 Participants
Tobacco Use Yes	57 participants n=5 Participants	42 participants n=7 Participants	99 participants n=5 Participants
Tobacco Use No	206 participants n=5 Participants	225 participants n=7 Participants	431 participants n=5 Participants
Beck Anxiety Inventory (BAI) Total Score	12.83 units on a scale STANDARD_DEVIATION 9.28 • n=5 Participants	13.18 units on a scale STANDARD_DEVIATION 9.77 • n=7 Participants	13.00 units on a scale STANDARD_DEVIATION 9.52 • n=5 Participants
Beck Depression Inventory II (BDI-II) Total Score	16.16 units on a scale STANDARD_DEVIATION 10.43 • n=5 Participants	16.20 units on a scale STANDARD_DEVIATION 10.35 • n=7 Participants	16.18 units on a scale STANDARD_DEVIATION 10.38 • n=5 Participants
Brief Pain Inventory (BPI) Average Pain Score	6.45 units on a scale STANDARD_DEVIATION 1.54 • n=5 Participants	6.46 units on a scale STANDARD_DEVIATION 1.62 • n=7 Participants	6.45 units on a scale STANDARD_DEVIATION 1.58 • n=5 Participants
Height	163.00 centimeters (cm) STANDARD_DEVIATION 8.38 • n=5 Participants	163.75 centimeters (cm) STANDARD_DEVIATION 8.48 • n=7 Participants	163.38 centimeters (cm) STANDARD_DEVIATION 8.43 • n=5 Participants
Likert Scale Rating of Mood, Anxiety, Sleep, Pain, and Stiffness Anxiety	3.68 units on a scale STANDARD_DEVIATION 2.81 • n=5 Participants	4.08 units on a scale STANDARD_DEVIATION 2.90 • n=7 Participants	3.88 units on a scale STANDARD_DEVIATION 2.86 • n=5 Participants
Likert Scale Rating of Mood, Anxiety, Sleep, Pain, and Stiffness Mood	3.78 units on a scale STANDARD_DEVIATION 2.76 • n=5 Participants	4.04 units on a scale STANDARD_DEVIATION 2.77 • n=7 Participants	3.91 units on a scale STANDARD_DEVIATION 2.77 • n=5 Participants
Likert Scale Rating of Mood, Anxiety, Sleep, Pain, and Stiffness Pain	7.25 units on a scale STANDARD_DEVIATION 1.87 • n=5 Participants	7.45 units on a scale STANDARD_DEVIATION 1.83 • n=7 Participants	7.35 units on a scale STANDARD_DEVIATION 1.85 • n=5 Participants
Likert Scale Rating of Mood, Anxiety, Sleep, Pain, and Stiffness Sleep	6.74 units on a scale STANDARD_DEVIATION 2.56 • n=5 Participants	6.81 units on a scale STANDARD_DEVIATION 2.67 • n=7 Participants	6.78 units on a scale STANDARD_DEVIATION 2.62 • n=5 Participants
Likert Scale Rating of Mood, Anxiety, Sleep, Pain, and Stiffness Stiffness	7.02 units on a scale STANDARD_DEVIATION 2.00 • n=5 Participants	7.12 units on a scale STANDARD_DEVIATION 1.84 • n=7 Participants	7.07 units on a scale STANDARD_DEVIATION 1.92 • n=5 Participants
Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (MGH-CPFQ) Total	26.71 units on a scale STANDARD_DEVIATION 6.33 • n=5 Participants	26.63 units on a scale STANDARD_DEVIATION 6.29 • n=7 Participants	26.67 units on a scale STANDARD_DEVIATION 6.30 • n=5 Participants
Patient's Global Impressions of Severity (PGI-S)	3.88 units on a scale STANDARD_DEVIATION 1.24 • n=5 Participants	3.66 units on a scale STANDARD_DEVIATION 1.43 • n=7 Participants	3.77 units on a scale STANDARD_DEVIATION 1.34 • n=5 Participants
The Multidimensional Fatigue Inventory (MFI) Dimension Scores General Fatigue Dimension	17.05 units on a scale STANDARD_DEVIATION 2.91 • n=5 Participants	17.16 units on a scale STANDARD_DEVIATION 2.87 • n=7 Participants	17.11 units on a scale STANDARD_DEVIATION 2.89 • n=5 Participants
The Multidimensional Fatigue Inventory (MFI) Dimension Scores Mental Fatigue Dimension	13.28 units on a scale STANDARD_DEVIATION 4.17 • n=5 Participants	12.97 units on a scale STANDARD_DEVIATION 4.30 • n=7 Participants	13.12 units on a scale STANDARD_DEVIATION 4.24 • n=5 Participants
The Multidimensional Fatigue Inventory (MFI) Dimension Scores Physical Fatigue Dimension	15.48 units on a scale STANDARD_DEVIATION 3.50 • n=5 Participants	15.40 units on a scale STANDARD_DEVIATION 3.61 • n=7 Participants	15.44 units on a scale STANDARD_DEVIATION 3.55 • n=5 Participants
The Multidimensional Fatigue Inventory (MFI) Dimension Scores Reduced Activity Dimension	13.78 units on a scale STANDARD_DEVIATION 4.06 • n=5 Participants	13.57 units on a scale STANDARD_DEVIATION 3.90 • n=7 Participants	13.67 units on a scale STANDARD_DEVIATION 3.98 • n=5 Participants
The Multidimensional Fatigue Inventory (MFI) Dimension Scores Reduced Motivation Dimension	12.41 units on a scale STANDARD_DEVIATION 3.69 • n=5 Participants	12.59 units on a scale STANDARD_DEVIATION 3.70 • n=7 Participants	12.50 units on a scale STANDARD_DEVIATION 3.70 • n=5 Participants
Weight	84.01 kilograms (kg) STANDARD_DEVIATION 19.76 • n=5 Participants	85.98 kilograms (kg) STANDARD_DEVIATION 21.65 • n=7 Participants	85.00 kilograms (kg) STANDARD_DEVIATION 20.74 • n=5 Participants

PRIMARY outcome

Timeframe: 12 weeks

Population: Number of randomized patients with baseline PGI-S and at least one post-baseline PGI-I data.

The PGI-Improvement scale is a patient-rated instrument that measures perceived improvement in symptoms. It is a 7-point scale where a score of 1 indicates that the patient is "very much improved," a score of 4 indicates that the patient has experienced "no change," and a score of 7 indicates that the patient is "very much worse."

Outcome measures

Measure	Duloxetine n=245 Participants 60-120 mg, oral, daily, 12 weeks	Placebo n=255 Participants oral, daily, 12 weeks
Patient's Global Impressions of Improvement (PGI-I) at Week 12	2.79 units on a scale Standard Error 0.10	3.36 units on a scale Standard Error 0.09

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Number of patients with a non-missing baseline and at least one post-baseline record. Last observation carried forward.

BPI is a self-reported form that assesses severity of pain and the interference of pain on function. There are 4 questions assessing the severity for worst pain, least pain, and average pain in the past 24 hours, and the pain right now. Severity scores range from 0 (no pain) to 10 (pain as bad as you can imagine). 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. Interference scores range from 0 (does not interfere) to 10 (completely interferes).

Outcome measures

Measure	Duloxetine n=249 Participants 60-120 mg, oral, daily, 12 weeks	Placebo n=258 Participants oral, daily, 12 weeks
Change From Baseline in Brief Pain Inventory (BPI) (Modified Short Form) at 12 Week Endpoint Worst Pain Severity	-2.32 units on a scale Standard Error 0.17	-1.57 units on a scale Standard Error 0.17
Change From Baseline in Brief Pain Inventory (BPI) (Modified Short Form) at 12 Week Endpoint Least Pain Severity	-1.57 units on a scale Standard Error 0.14	-0.96 units on a scale Standard Error 0.14
Change From Baseline in Brief Pain Inventory (BPI) (Modified Short Form) at 12 Week Endpoint Average Pain Severity	-2.14 units on a scale Standard Error 0.15	-1.40 units on a scale Standard Error 0.15
Change From Baseline in Brief Pain Inventory (BPI) (Modified Short Form) at 12 Week Endpoint Pain Right Now Severity	-2.10 units on a scale Standard Error 0.17	-1.34 units on a scale Standard Error 0.17
Change From Baseline in Brief Pain Inventory (BPI) (Modified Short Form) at 12 Week Endpoint General Activity Interference	-2.38 units on a scale Standard Error 0.17	-1.44 units on a scale Standard Error 0.17
Change From Baseline in Brief Pain Inventory (BPI) (Modified Short Form) at 12 Week Endpoint Mood Interference	-2.56 units on a scale Standard Error 0.18	-1.61 units on a scale Standard Error 0.18
Change From Baseline in Brief Pain Inventory (BPI) (Modified Short Form) at 12 Week Endpoint Walking Ability Interference	-2.16 units on a scale Standard Error 0.17	-1.36 units on a scale Standard Error 0.17
Change From Baseline in Brief Pain Inventory (BPI) (Modified Short Form) at 12 Week Endpoint Normal Work Interference	-2.37 units on a scale Standard Error 0.17	-1.60 units on a scale Standard Error 0.17
Change From Baseline in Brief Pain Inventory (BPI) (Modified Short Form) at 12 Week Endpoint Relations with Other People Interference	-2.17 units on a scale Standard Error 0.17	-1.22 units on a scale Standard Error 0.16
Change From Baseline in Brief Pain Inventory (BPI) (Modified Short Form) at 12 Week Endpoint Sleep Interference	-2.69 units on a scale Standard Error 0.18	-1.81 units on a scale Standard Error 0.18
Change From Baseline in Brief Pain Inventory (BPI) (Modified Short Form) at 12 Week Endpoint Enjoyment of Life Interference	-2.84 units on a scale Standard Error 0.19	-1.45 units on a scale Standard Error 0.19
Change From Baseline in Brief Pain Inventory (BPI) (Modified Short Form) at 12 Week Endpoint Average Interference	-2.44 units on a scale Standard Error 0.16	-1.52 units on a scale Standard Error 0.15

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Number of patients with a non-missing baseline and at least one post-baseline record.

MFI is a 20-item, self-reporting instrument designed to collect data on the following 5 dimensions: general fatigue, physical fatigue, mental fatigue, reduced motivation, and reduced activity. Each dimension score is derived by summing the scores of the 4 individual items that pertain to each dimension. Item scores range from 1 to 5; thus, dimensional scores range from 4 to 20 with a higher score reflecting greater levels of fatigue.

Outcome measures

Measure	Duloxetine n=246 Participants 60-120 mg, oral, daily, 12 weeks	Placebo n=254 Participants oral, daily, 12 weeks
Change From Baseline in Multidimensional Fatigue Inventory (MFI) at 12 Week Endpoint General Fatigue	-2.21 units on a scale Standard Error 0.22	-1.38 units on a scale Standard Error 0.22
Change From Baseline in Multidimensional Fatigue Inventory (MFI) at 12 Week Endpoint Physical Fatigue	-2.08 units on a scale Standard Error 0.22	-1.35 units on a scale Standard Error 0.22
Change From Baseline in Multidimensional Fatigue Inventory (MFI) at 12 Week Endpoint Mental Fatigue	-2.01 units on a scale Standard Error 0.23	-1.09 units on a scale Standard Error 0.23
Change From Baseline in Multidimensional Fatigue Inventory (MFI) at 12 Week Endpoint Reduced Activity	-1.46 units on a scale Standard Error 0.24	-0.59 units on a scale Standard Error 0.23
Change From Baseline in Multidimensional Fatigue Inventory (MFI) at 12 Week Endpoint Reduced Motivation	-1.66 units on a scale Standard Error 0.22	-0.72 units on a scale Standard Error 0.21

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Number of patients with a non-missing baseline and at least one post-baseline record.

BDI-II is a 21-item patient-completed questionnaire designed to assess characteristics of depression. Each item is rated on a 4-point scale (0 = not present; 3 = present in the extreme). This questionnaire will be used to rate the severity of depressive symptoms and any improvement during the course of the trial. The total score ranges from 0 to 63; the higher the score, the more severe the depressive symptoms.

Outcome measures

Measure	Duloxetine n=233 Participants 60-120 mg, oral, daily, 12 weeks	Placebo n=237 Participants oral, daily, 12 weeks
Change From Baseline in Beck Depression Inventory-II (BDI-II) at 12 Week Endpoint	-5.53 units on a scale Standard Error 0.53	-3.63 units on a scale Standard Error 0.52

SECONDARY outcome

Timeframe: Baseline, 12 Weeks

Population: Number of patients with a non-missing baseline and at least one post-baseline record.

The Clinical Global Impressions of Severity (CGI-Severity) scale evaluates the severity of illness at the time of assessment. The score ranges from 1 (normal, not at all ill) to 7 (among the most extremely ill patients).

Outcome measures

Measure	Duloxetine n=231 Participants 60-120 mg, oral, daily, 12 weeks	Placebo n=237 Participants oral, daily, 12 weeks
Change From Baseline in Clinical Global Impressions of Severity (CGI-S) at 12 Week Endpoint	-1.05 units on a scale Standard Error 0.07	-0.71 units on a scale Standard Error 0.07

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Number of patients with a non-missing baseline and at least one post-baseline record.

BAI is a 21-item patient-completed questionnaire designed to assess characteristics of anxiety. Each item is rated on a 4-point scale (0 = not present; 3 = present in the extreme). This questionnaire will be used to rate the severity of anxiety symptoms and any improvement during the course of the trial. The total score ranges from 0 to 63; the higher the score, the more severe the anxiety symptoms.

Outcome measures

Measure	Duloxetine n=230 Participants 60-120 mg, oral, daily, 12 weeks	Placebo n=232 Participants oral, daily, 12 weeks
Change From Baseline in Beck Anxiety Inventory (BAI) at 12 Week Endpoint	-3.14 units on a scale Standard Error 0.46	-3.22 units on a scale Standard Error 0.46

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Number of patients with a non-missing baseline and at least one post-baseline record.

The patient-rated SF-36 consists of 36 questions covering eight health domains: physical functioning, bodily pain, role limitations due to physical problems, role limitations due to emotional problems, general health perceptions, mental health, social function, and vitality. Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale, with higher scores indicating better health status or functioning. Two summary scores: the Physical Component Summary and the Mental Component Summary are constructed based on the eight SF-36 domains.

Outcome measures

Measure	Duloxetine n=232 Participants 60-120 mg, oral, daily, 12 weeks	Placebo n=235 Participants oral, daily, 12 weeks
Change From Baseline in 36-Item Short-form Health Survey (SF-36) at 12 Weeks Bodily Pain	18.48 units on a scale Standard Error 1.33	13.26 units on a scale Standard Error 1.32
Change From Baseline in 36-Item Short-form Health Survey (SF-36) at 12 Weeks General Health	9.33 units on a scale Standard Error 1.16	2.91 units on a scale Standard Error 1.15
Change From Baseline in 36-Item Short-form Health Survey (SF-36) at 12 Weeks Mental Health	10.05 units on a scale Standard Error 1.17	2.61 units on a scale Standard Error 1.15
Change From Baseline in 36-Item Short-form Health Survey (SF-36) at 12 Weeks Physical Functioning	13.52 units on a scale Standard Error 1.31	8.06 units on a scale Standard Error 1.30
Change From Baseline in 36-Item Short-form Health Survey (SF-36) at 12 Weeks Role-Emotional	14.91 units on a scale Standard Error 2.57	5.13 units on a scale Standard Error 2.54
Change From Baseline in 36-Item Short-form Health Survey (SF-36) at 12 Weeks Role-Physical	20.49 units on a scale Standard Error 2.51	18.90 units on a scale Standard Error 2.48
Change From Baseline in 36-Item Short-form Health Survey (SF-36) at 12 Weeks Social Functioning	14.16 units on a scale Standard Error 1.52	7.49 units on a scale Standard Error 1.50
Change From Baseline in 36-Item Short-form Health Survey (SF-36) at 12 Weeks Vitality	12.78 units on a scale Standard Error 1.34	8.47 units on a scale Standard Error 1.32
Change From Baseline in 36-Item Short-form Health Survey (SF-36) at 12 Weeks Physical Component Summary (PCS)	5.96 units on a scale Standard Error 0.58	4.81 units on a scale Standard Error 0.57
Change From Baseline in 36-Item Short-form Health Survey (SF-36) at 12 Weeks Mental Component Summary (MCS)	5.11 units on a scale Standard Error 0.69	1.28 units on a scale Standard Error 0.68

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Number of patients with a non-missing baseline and at least one post-baseline record.

The MGH-CPFQ is a self-report instrument consisting of seven questions pertaining to an individual's cognitive and physical well-being. Each question is rated 1 = "greater than normal" to 6 = "totally absent". Total score ranges from 7 to 42.

Outcome measures

Measure	Duloxetine n=246 Participants 60-120 mg, oral, daily, 12 weeks	Placebo n=254 Participants oral, daily, 12 weeks
Change From Baseline in Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (MGH-CPFQ) Total Score at 12 Week Endpoint	-4.88 units on a scale Standard Error 0.42	-3.92 units on a scale Standard Error 0.41

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Number of patients with a non-missing baseline and at least one post-baseline record.

Likert scales are patient-rated assessments. Mood: feeling low, sad or depressed; rated 0 = not feeling low, sad or depressed to 10 = feeling extremely low, sad or depressed. Anxious: anxious feelings; rated 0 = not feeling anxious to 10 = extremely anxious. Sleep: how much patient bothered by sleep difficulties; rated 0 = not bothered to 10 = extremely bothered. Pain: how much patient bothered by painful physical discomforts; rated 0 = not bothered to 10 = extremely bothered. Stiffness: how stiff patient felt in past 24 hours; rated 0 = not felt any stiffness to 10 = felt extremely stiff.

Outcome measures

Measure	Duloxetine n=249 Participants 60-120 mg, oral, daily, 12 weeks	Placebo n=258 Participants oral, daily, 12 weeks
Change From Baseline in the Mood, Anxiety, Pain, Sleep, and Stiffness Likert Scale at 12 Week Endpoint Mood	-1.27 units on a scale Standard Error 0.17	-0.52 units on a scale Standard Error 0.16
Change From Baseline in the Mood, Anxiety, Pain, Sleep, and Stiffness Likert Scale at 12 Week Endpoint Anxiety	-1.22 units on a scale Standard Error 0.16	-0.58 units on a scale Standard Error 0.16
Change From Baseline in the Mood, Anxiety, Pain, Sleep, and Stiffness Likert Scale at 12 Week Endpoint Pain	-2.45 units on a scale Standard Error 0.18	-1.73 units on a scale Standard Error 0.18
Change From Baseline in the Mood, Anxiety, Pain, Sleep, and Stiffness Likert Scale at 12 Week Endpoint Sleep	-1.96 units on a scale Standard Error 0.19	-1.47 units on a scale Standard Error 0.18
Change From Baseline in the Mood, Anxiety, Pain, Sleep, and Stiffness Likert Scale at 12 Week Endpoint Stiffness	-2.54 units on a scale Standard Error 0.17	-1.67 units on a scale Standard Error 0.17

SECONDARY outcome

Timeframe: 12 Weeks

Population: Number of randomized patients with baseline and at least one post-baseline data.

Response was defined as at least 30% reduction from baseline to endpoint (last observation carried forward) for BPI average pain score. BPI average pain score assesses the severity of the average pain in the past 24 hours. The average severity score ranges from 0 (no pain) to 10 (pain as bad as you can imagine).

Outcome measures

Measure	Duloxetine n=249 Participants 60-120 mg, oral, daily, 12 weeks	Placebo n=258 Participants oral, daily, 12 weeks
Number of Responders: 30% Improvement in Brief Pain Inventory Average Pain at 12 Week Endpoint	119 participants	88 participants

SECONDARY outcome

Timeframe: 12 weeks

Population: Number of randomized patients with baseline and at least one post-baseline data.

Response was defined as at least 50% reduction from baseline to endpoint (last observation carried forward) for BPI average pain score. BPI average pain score assesses the severity of the average pain in the past 24 hours. The average severity score ranges from 0 (no pain) to 10 (pain as bad as you can imagine).

Outcome measures

Measure	Duloxetine n=249 Participants 60-120 mg, oral, daily, 12 weeks	Placebo n=258 Participants oral, daily, 12 weeks
Number of Responders: 50% Improvement in Brief Pain Inventory Average Pain Score at 12 Week Endpoint	83 participants	55 participants

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Number of patients with a baseline and at least one post-baseline result.

Outcome measures

Measure	Duloxetine n=250 Participants 60-120 mg, oral, daily, 12 weeks	Placebo n=259 Participants oral, daily, 12 weeks
Change From Baseline in Blood Pressure at 12 Week Endpoint Systolic Blood Pressure (SBP)	1.09 mm Hg Standard Error 0.80	-0.72 mm Hg Standard Error 0.78
Change From Baseline in Blood Pressure at 12 Week Endpoint Diastolic Blood Pressure (DBP)	0.83 mm Hg Standard Error 0.51	0.31 mm Hg Standard Error 0.50

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Number of patients with a baseline and at least one post-baseline result.

Outcome measures

Measure	Duloxetine n=250 Participants 60-120 mg, oral, daily, 12 weeks	Placebo n=259 Participants oral, daily, 12 weeks
Change From Baseline in Heart Rate at 12 Week Endpoint	1.76 beats per minute (bpm) Standard Error 0.50	-0.20 beats per minute (bpm) Standard Error 0.49

SECONDARY outcome

Timeframe: Baseline through 12 Weeks

Population: Number of randomized patients.

C-SSRS: scale capturing occurrence, severity, and frequency of suicide-related thoughts and behaviors. Number of patients 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, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation: a "yes" answer to any one of 5 suicidal ideation questions, which includes wish to be dead, and 4 different categories of active suicidal ideation. Suicidal act: a "yes" answer to actual attempt or completed suicide.

Outcome measures

Measure	Duloxetine n=263 Participants 60-120 mg, oral, daily, 12 weeks	Placebo n=267 Participants oral, daily, 12 weeks
Number of Patients With Columbia Suicide Severity Rating Scale (CSSR-S) Events (Behaviors, Ideations, Acts) Suicidal Ideation	6 participants	7 participants
Number of Patients With Columbia Suicide Severity Rating Scale (CSSR-S) Events (Behaviors, Ideations, Acts) Suicidal Behavior	0 participants	0 participants
Number of Patients With Columbia Suicide Severity Rating Scale (CSSR-S) Events (Behaviors, Ideations, Acts) Suicidal Acts	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Number of patients with a baseline and at least one post-baseline result.

Outcome measures

Measure	Duloxetine n=249 Participants 60-120 mg, oral, daily, 12 weeks	Placebo n=259 Participants oral, daily, 12 weeks
Change From Baseline in Weight at 12 Week Endpoint	-0.62 kilograms (kg) Standard Error 0.15	0.21 kilograms (kg) Standard Error 0.14

Adverse Events

Duloxetine

Serious events: 1 serious events

Other events: 217 other events

Deaths: 0 deaths

Placebo

Serious events: 6 serious events

Other events: 189 other events

Deaths: 0 deaths

Serious adverse events

Measure	Duloxetine n=263 participants at risk 60-120 mg, oral, daily, 12 weeks	Placebo n=267 participants at risk oral, daily, 12 weeks
Cardiac disorders Myocardial infarction	0.00% 0/263 • These are the adverse events which occurred during the 12 week acute double-blind phase.	0.37% 1/267 • Number of events 1 • These are the adverse events which occurred during the 12 week acute double-blind phase.
Gastrointestinal disorders Pancreatitis	0.00% 0/263 • These are the adverse events which occurred during the 12 week acute double-blind phase.	0.37% 1/267 • Number of events 1 • These are the adverse events which occurred during the 12 week acute double-blind phase.
General disorders Chest pain	0.00% 0/263 • These are the adverse events which occurred during the 12 week acute double-blind phase.	0.37% 1/267 • Number of events 1 • These are the adverse events which occurred during the 12 week acute double-blind phase.
General disorders Non-cardiac chest pain	0.00% 0/263 • These are the adverse events which occurred during the 12 week acute double-blind phase.	0.37% 1/267 • Number of events 1 • These are the adverse events which occurred during the 12 week acute double-blind phase.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.38% 1/263 • Number of events 1 • These are the adverse events which occurred during the 12 week acute double-blind phase.	0.00% 0/267 • These are the adverse events which occurred during the 12 week acute double-blind phase.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/263 • These are the adverse events which occurred during the 12 week acute double-blind phase.	0.37% 1/267 • Number of events 1 • These are the adverse events which occurred during the 12 week acute double-blind phase.
Psychiatric disorders Suicidal ideation	0.00% 0/263 • These are the adverse events which occurred during the 12 week acute double-blind phase.	0.37% 1/267 • Number of events 1 • These are the adverse events which occurred during the 12 week acute double-blind phase.

Other adverse events

Measure	Duloxetine n=263 participants at risk 60-120 mg, oral, daily, 12 weeks	Placebo n=267 participants at risk oral, daily, 12 weeks
Gastrointestinal disorders Constipation	13.3% 35/263 • Number of events 35 • These are the adverse events which occurred during the 12 week acute double-blind phase.	4.1% 11/267 • Number of events 11 • These are the adverse events which occurred during the 12 week acute double-blind phase.
Gastrointestinal disorders Diarrhoea	10.3% 27/263 • Number of events 30 • These are the adverse events which occurred during the 12 week acute double-blind phase.	4.5% 12/267 • Number of events 12 • These are the adverse events which occurred during the 12 week acute double-blind phase.
Gastrointestinal disorders Dry mouth	11.8% 31/263 • Number of events 31 • These are the adverse events which occurred during the 12 week acute double-blind phase.	4.5% 12/267 • Number of events 12 • These are the adverse events which occurred during the 12 week acute double-blind phase.
Gastrointestinal disorders Nausea	31.6% 83/263 • Number of events 87 • These are the adverse events which occurred during the 12 week acute double-blind phase.	9.7% 26/267 • Number of events 28 • These are the adverse events which occurred during the 12 week acute double-blind phase.
Gastrointestinal disorders Vomiting	4.6% 12/263 • Number of events 15 • These are the adverse events which occurred during the 12 week acute double-blind phase.	0.75% 2/267 • Number of events 2 • These are the adverse events which occurred during the 12 week acute double-blind phase.
General disorders Fatigue	9.5% 25/263 • Number of events 26 • These are the adverse events which occurred during the 12 week acute double-blind phase.	7.1% 19/267 • Number of events 19 • These are the adverse events which occurred during the 12 week acute double-blind phase.
Infections and infestations Upper respiratory tract infection	4.9% 13/263 • Number of events 13 • These are the adverse events which occurred during the 12 week acute double-blind phase.	4.9% 13/267 • Number of events 14 • These are the adverse events which occurred during the 12 week acute double-blind phase.
Metabolism and nutrition disorders Decreased appetite	4.9% 13/263 • Number of events 13 • These are the adverse events which occurred during the 12 week acute double-blind phase.	2.2% 6/267 • Number of events 6 • These are the adverse events which occurred during the 12 week acute double-blind phase.
Musculoskeletal and connective tissue disorders Pain in extremity	1.5% 4/263 • Number of events 4 • These are the adverse events which occurred during the 12 week acute double-blind phase.	4.1% 11/267 • Number of events 15 • These are the adverse events which occurred during the 12 week acute double-blind phase.
Nervous system disorders Dizziness	9.9% 26/263 • Number of events 27 • These are the adverse events which occurred during the 12 week acute double-blind phase.	5.2% 14/267 • Number of events 15 • These are the adverse events which occurred during the 12 week acute double-blind phase.
Nervous system disorders Headache	17.1% 45/263 • Number of events 48 • These are the adverse events which occurred during the 12 week acute double-blind phase.	9.0% 24/267 • Number of events 28 • These are the adverse events which occurred during the 12 week acute double-blind phase.
Nervous system disorders Somnolence	5.7% 15/263 • Number of events 16 • These are the adverse events which occurred during the 12 week acute double-blind phase.	3.4% 9/267 • Number of events 9 • These are the adverse events which occurred during the 12 week acute double-blind phase.
Musculoskeletal and connective tissue disorders Arthralgia	1.1% 3/263 • Number of events 3 • These are the adverse events which occurred during the 12 week acute double-blind phase.	4.1% 11/267 • Number of events 11 • These are the adverse events which occurred during the 12 week acute double-blind phase.
Psychiatric disorders Insomnia	9.1% 24/263 • Number of events 27 • These are the adverse events which occurred during the 12 week acute double-blind phase.	7.1% 19/267 • Number of events 20 • These are the adverse events which occurred during the 12 week acute double-blind phase.
Skin and subcutaneous tissue disorders Hyperhidrosis	8.7% 23/263 • Number of events 24 • These are the adverse events which occurred during the 12 week acute double-blind phase.	1.5% 4/267 • Number of events 4 • These are the adverse events which occurred during the 12 week acute double-blind phase.
Vascular disorders Hot flush	4.9% 13/263 • Number of events 14 • These are the adverse events which occurred during the 12 week acute double-blind phase.	0.75% 2/267 • Number of events 2 • These are the adverse events which occurred during the 12 week acute double-blind phase.
General disorders Irritability	1.1% 3/263 • Number of events 3 • These are the adverse events which occurred during the 12 week acute double-blind phase.	4.5% 12/267 • Number of events 12 • These are the adverse events which occurred during the 12 week acute double-blind phase.

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