Fibromyalgia
Conditions
Brief summary
The purpose of this study is to confirm the efficacy and safety of duloxetine 60-120 mg once daily in comparison to placebo on symptom improvement in patients meeting criteria for fibromyalgia aged 18 and older. Patients will be randomized to duloxetine or placebo, however, all patients will receive duloxetine at some point in the study.
Interventions
DRUGduloxetine hydrochloride
60-120 mg, oral, every day, 12 weeks (acute blinded phase followed by a 12 week blinded continuation phase).
DRUGplacebo
oral, daily, 12 weeks (acute blinded phase followed by 12 weeks of blinded duloxetine treatment)
Sponsors
Boehringer Ingelheim
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* male or female patients * aged 18 and older who meet criteria for fibromyalgia as defined by the American College of Rheumatology * have a score of at least 4 on the average pain item of the Brief Pain Inventory (BPI) (modified short form) at visits 1 and 2 * all females must test negative for pregnancy at the time of enrollment * have a degree of understanding such that the patient can provide informed consent, complete protocol required assessments and communicate intelligibly with the investigator and study coordinator.
Exclusion criteria
* have pain symptoms related to traumatic injury, structural rheumatic disease, or regional rheumatic disease that will interfere with interpretation of outcome measures * have regional pain syndrome, multiple surgeries or failed back syndrome * have confirmed current or previous diagnosis of rheumatoid arthritis, inflammatory arthritis, or infectious arthritis, or an autoimmune disease (i.e. systemic lupus erythematosus)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Patient's Global Impressions of Improvement (PGI-I) at Week 12 | 12 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Multidimensional Fatigue Inventory (MFI) at 12 Week Endpoint | Baseline, 12 weeks | 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. |
| Change From Baseline in Beck Depression Inventory-II (BDI-II) at 12 Week Endpoint | Baseline, 12 weeks | 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. |
| Change From Baseline in Clinical Global Impressions of Severity (CGI-S) at 12 Week Endpoint | Baseline, 12 Weeks | 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). |
| Change From Baseline in Beck Anxiety Inventory (BAI) at 12 Week Endpoint | Baseline, 12 weeks | 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. |
| Change From Baseline in 36-Item Short-form Health Survey (SF-36) at 12 Weeks | Baseline, 12 weeks | 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. |
| Change From Baseline in Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (MGH-CPFQ) Total Score at 12 Week Endpoint | Baseline, 12 weeks | 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. |
| Change From Baseline in Brief Pain Inventory (BPI) (Modified Short Form) at 12 Week Endpoint | Baseline, 12 weeks | 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). |
| Number of Responders: 30% Improvement in Brief Pain Inventory Average Pain at 12 Week Endpoint | 12 Weeks | 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). |
| Number of Responders: 50% Improvement in Brief Pain Inventory Average Pain Score at 12 Week Endpoint | 12 weeks | 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). |
| Change From Baseline in Blood Pressure at 12 Week Endpoint | Baseline, 12 weeks | — |
| Change From Baseline in Heart Rate at 12 Week Endpoint | Baseline, 12 weeks | — |
| Number of Patients With Columbia Suicide Severity Rating Scale (CSSR-S) Events (Behaviors, Ideations, Acts) | Baseline through 12 Weeks | 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. |
| Change From Baseline in Weight at 12 Week Endpoint | Baseline, 12 weeks | — |
| Change From Baseline in the Mood, Anxiety, Pain, Sleep, and Stiffness Likert Scale at 12 Week Endpoint | Baseline, 12 weeks | 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. |
Countries
Puerto Rico, United States
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Duloxetine 60-120 mg, oral, daily, 12 weeks | 263 |
| Placebo oral, daily, 12 weeks | 267 |
| Total | 530 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 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 | Death - Cervical vertebral fracture | 1 | 0 |
| Continuation Double-Blind Phase | Lack of Efficacy | 2 | 5 |
| Continuation Double-Blind Phase | Lost to Follow-up | 4 | 5 |
| Continuation Double-Blind Phase | Physician Decision | 2 | 0 |
| Continuation Double-Blind Phase | Protocol Violation | 2 | 3 |
| Continuation Double-Blind Phase | Sponsor Decision | 0 | 3 |
| Continuation Double-Blind Phase | Withdrawal by Subject | 9 | 5 |
Baseline characteristics
| Characteristic | Duloxetine | Total | Placebo |
|---|---|---|---|
| Age Continuous | 50.74 years STANDARD_DEVIATION 11.26 | 50.18 years STANDARD_DEVIATION 11.05 | 49.62 years STANDARD_DEVIATION 10.84 |
| Alcohol Consumption No | 174 participants | 351 participants | 177 participants |
| Alcohol Consumption Yes | 89 participants | 179 participants | 90 participants |
| Beck Anxiety Inventory (BAI) Total Score | 12.83 units on a scale STANDARD_DEVIATION 9.28 | 13.00 units on a scale STANDARD_DEVIATION 9.52 | 13.18 units on a scale STANDARD_DEVIATION 9.77 |
| Beck Depression Inventory II (BDI-II) Total Score | 16.16 units on a scale STANDARD_DEVIATION 10.43 | 16.18 units on a scale STANDARD_DEVIATION 10.38 | 16.20 units on a scale STANDARD_DEVIATION 10.35 |
| Brief Pain Inventory (BPI) Average Pain Score | 6.45 units on a scale STANDARD_DEVIATION 1.54 | 6.45 units on a scale STANDARD_DEVIATION 1.58 | 6.46 units on a scale STANDARD_DEVIATION 1.62 |
| Generalized Anxiety Disorder (GAD) Status No | 244 participants | 487 participants | 243 participants |
| Generalized Anxiety Disorder (GAD) Status Yes | 19 participants | 43 participants | 24 participants |
| Height | 163.00 centimeters (cm) STANDARD_DEVIATION 8.38 | 163.38 centimeters (cm) STANDARD_DEVIATION 8.43 | 163.75 centimeters (cm) STANDARD_DEVIATION 8.48 |
| Likert Scale Rating of Mood, Anxiety, Sleep, Pain, and Stiffness Anxiety | 3.68 units on a scale STANDARD_DEVIATION 2.81 | 3.88 units on a scale STANDARD_DEVIATION 2.86 | 4.08 units on a scale STANDARD_DEVIATION 2.9 |
| Likert Scale Rating of Mood, Anxiety, Sleep, Pain, and Stiffness Mood | 3.78 units on a scale STANDARD_DEVIATION 2.76 | 3.91 units on a scale STANDARD_DEVIATION 2.77 | 4.04 units on a scale STANDARD_DEVIATION 2.77 |
| Likert Scale Rating of Mood, Anxiety, Sleep, Pain, and Stiffness Pain | 7.25 units on a scale STANDARD_DEVIATION 1.87 | 7.35 units on a scale STANDARD_DEVIATION 1.85 | 7.45 units on a scale STANDARD_DEVIATION 1.83 |
| Likert Scale Rating of Mood, Anxiety, Sleep, Pain, and Stiffness Sleep | 6.74 units on a scale STANDARD_DEVIATION 2.56 | 6.78 units on a scale STANDARD_DEVIATION 2.62 | 6.81 units on a scale STANDARD_DEVIATION 2.67 |
| Likert Scale Rating of Mood, Anxiety, Sleep, Pain, and Stiffness Stiffness | 7.02 units on a scale STANDARD_DEVIATION 2 | 7.07 units on a scale STANDARD_DEVIATION 1.92 | 7.12 units on a scale STANDARD_DEVIATION 1.84 |
| Major Depressive Disorder (MDD) Status No | 219 participants | 433 participants | 214 participants |
| Major Depressive Disorder (MDD) Status Yes | 44 participants | 97 participants | 53 participants |
| Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (MGH-CPFQ) Total | 26.71 units on a scale STANDARD_DEVIATION 6.33 | 26.67 units on a scale STANDARD_DEVIATION 6.3 | 26.63 units on a scale STANDARD_DEVIATION 6.29 |
| Patient's Global Impressions of Severity (PGI-S) | 3.88 units on a scale STANDARD_DEVIATION 1.24 | 3.77 units on a scale STANDARD_DEVIATION 1.34 | 3.66 units on a scale STANDARD_DEVIATION 1.43 |
| Race/Ethnicity, Customized Caucasian | 204 participants | 410 participants | 206 participants |
| Race/Ethnicity, Customized Hispanic | 37 participants | 83 participants | 46 participants |
| Race/Ethnicity, Customized Other - Not Specified | 22 participants | 37 participants | 15 participants |
| Region of Enrollment United States | 263 participants | 530 participants | 267 participants |
| Sex: Female, Male Female | 244 Participants | 494 Participants | 250 Participants |
| Sex: Female, Male Male | 19 Participants | 36 Participants | 17 Participants |
| The Multidimensional Fatigue Inventory (MFI) Dimension Scores General Fatigue Dimension | 17.05 units on a scale STANDARD_DEVIATION 2.91 | 17.11 units on a scale STANDARD_DEVIATION 2.89 | 17.16 units on a scale STANDARD_DEVIATION 2.87 |
| The Multidimensional Fatigue Inventory (MFI) Dimension Scores Mental Fatigue Dimension | 13.28 units on a scale STANDARD_DEVIATION 4.17 | 13.12 units on a scale STANDARD_DEVIATION 4.24 | 12.97 units on a scale STANDARD_DEVIATION 4.3 |
| The Multidimensional Fatigue Inventory (MFI) Dimension Scores Physical Fatigue Dimension | 15.48 units on a scale STANDARD_DEVIATION 3.5 | 15.44 units on a scale STANDARD_DEVIATION 3.55 | 15.40 units on a scale STANDARD_DEVIATION 3.61 |
| The Multidimensional Fatigue Inventory (MFI) Dimension Scores Reduced Activity Dimension | 13.78 units on a scale STANDARD_DEVIATION 4.06 | 13.67 units on a scale STANDARD_DEVIATION 3.98 | 13.57 units on a scale STANDARD_DEVIATION 3.9 |
| The Multidimensional Fatigue Inventory (MFI) Dimension Scores Reduced Motivation Dimension | 12.41 units on a scale STANDARD_DEVIATION 3.69 | 12.50 units on a scale STANDARD_DEVIATION 3.7 | 12.59 units on a scale STANDARD_DEVIATION 3.7 |
| Tobacco Use No | 206 participants | 431 participants | 225 participants |
| Tobacco Use Yes | 57 participants | 99 participants | 42 participants |
| Weight | 84.01 kilograms (kg) STANDARD_DEVIATION 19.76 | 85.00 kilograms (kg) STANDARD_DEVIATION 20.74 | 85.98 kilograms (kg) STANDARD_DEVIATION 21.65 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 217 / 263 | 189 / 267 |
| serious Total, serious adverse events | 1 / 263 | 6 / 267 |
Outcome results
Primary
Patient's Global Impressions of Improvement (PGI-I) at Week 12
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.
Time frame: 12 weeks
Population: Number of randomized patients with baseline PGI-S and at least one post-baseline PGI-I data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine | Patient's Global Impressions of Improvement (PGI-I) at Week 12 | 2.79 units on a scale | Standard Error 0.1 |
| Placebo | Patient's Global Impressions of Improvement (PGI-I) at Week 12 | 3.36 units on a scale | Standard Error 0.09 |
Comparison: Patients treated with 60-120 mg duloxetine for 12 weeks compared with placebo will show greater improvement in symptoms as assessed by Patient's Global Impressions of Improvement (PGI-I). Sample size determined using 2-sided t-test with significance level of 0.05, and discontinuation rate of 5% without postbaseline data. With 261 patients per arm, study has approximately 85% power to detect treatment group difference of -0.4 points (standard deviation of 1.5) in PGI-I between treatment groups.p-value: <0.001Mixed Models Analysis
Secondary
Change From Baseline in 36-Item Short-form Health Survey (SF-36) at 12 Weeks
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.
Time frame: Baseline, 12 weeks
Population: Number of patients with a non-missing baseline and at least one post-baseline record.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine | 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 |
| Duloxetine | 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 |
| Duloxetine | 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 |
| Duloxetine | 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 |
| Duloxetine | 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 |
| Duloxetine | 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 |
| Duloxetine | 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 |
| Duloxetine | 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 |
| Duloxetine | 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 |
| Duloxetine | 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 |
| Placebo | Change From Baseline in 36-Item Short-form Health Survey (SF-36) at 12 Weeks | Vitality | 8.47 units on a scale | Standard Error 1.32 |
| Placebo | Change From Baseline in 36-Item Short-form Health Survey (SF-36) at 12 Weeks | Bodily Pain | 13.26 units on a scale | Standard Error 1.32 |
| Placebo | Change From Baseline in 36-Item Short-form Health Survey (SF-36) at 12 Weeks | Role-Physical | 18.90 units on a scale | Standard Error 2.48 |
| Placebo | Change From Baseline in 36-Item Short-form Health Survey (SF-36) at 12 Weeks | General Health | 2.91 units on a scale | Standard Error 1.15 |
| Placebo | Change From Baseline in 36-Item Short-form Health Survey (SF-36) at 12 Weeks | Mental Component Summary (MCS) | 1.28 units on a scale | Standard Error 0.68 |
| Placebo | Change From Baseline in 36-Item Short-form Health Survey (SF-36) at 12 Weeks | Mental Health | 2.61 units on a scale | Standard Error 1.15 |
| Placebo | Change From Baseline in 36-Item Short-form Health Survey (SF-36) at 12 Weeks | Social Functioning | 7.49 units on a scale | Standard Error 1.5 |
| Placebo | Change From Baseline in 36-Item Short-form Health Survey (SF-36) at 12 Weeks | Physical Functioning | 8.06 units on a scale | Standard Error 1.3 |
| Placebo | Change From Baseline in 36-Item Short-form Health Survey (SF-36) at 12 Weeks | Physical Component Summary (PCS) | 4.81 units on a scale | Standard Error 0.57 |
| Placebo | Change From Baseline in 36-Item Short-form Health Survey (SF-36) at 12 Weeks | Role-Emotional | 5.13 units on a scale | Standard Error 2.54 |
p-value: 0.00395% CI: [1.76, 8.67]ANCOVA
p-value: <0.00195% CI: [3.41, 9.43]ANCOVA
p-value: <0.00195% CI: [4.41, 10.47]ANCOVA
p-value: 0.00295% CI: [2.06, 8.88]ANCOVA
p-value: 0.00495% CI: [3.11, 16.45]ANCOVA
p-value: 0.63295% CI: [-4.93, 8.11]ANCOVA
p-value: <0.00195% CI: [2.73, 10.61]ANCOVA
p-value: 0.01595% CI: [0.84, 7.79]ANCOVA
p-value: 0.13495% CI: [-0.35, 2.64]ANCOVA
p-value: <0.00195% CI: [2.05, 5.6]ANCOVA
Secondary
Change From Baseline in Beck Anxiety Inventory (BAI) at 12 Week Endpoint
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.
Time frame: Baseline, 12 weeks
Population: Number of patients with a non-missing baseline and at least one post-baseline record.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine | Change From Baseline in Beck Anxiety Inventory (BAI) at 12 Week Endpoint | -3.14 units on a scale | Standard Error 0.46 |
| Placebo | Change From Baseline in Beck Anxiety Inventory (BAI) at 12 Week Endpoint | -3.22 units on a scale | Standard Error 0.46 |
p-value: 0.90795% CI: [-1.13, 1.27]ANCOVA
Secondary
Change From Baseline in Beck Depression Inventory-II (BDI-II) at 12 Week Endpoint
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.
Time frame: Baseline, 12 weeks
Population: Number of patients with a non-missing baseline and at least one post-baseline record.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine | Change From Baseline in Beck Depression Inventory-II (BDI-II) at 12 Week Endpoint | -5.53 units on a scale | Standard Error 0.53 |
| Placebo | Change From Baseline in Beck Depression Inventory-II (BDI-II) at 12 Week Endpoint | -3.63 units on a scale | Standard Error 0.52 |
p-value: 0.00795% CI: [-3.25, -0.53]ANCOVA
Secondary
Change From Baseline in Blood Pressure at 12 Week Endpoint
Time frame: Baseline, 12 weeks
Population: Number of patients with a baseline and at least one post-baseline result.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine | Change From Baseline in Blood Pressure at 12 Week Endpoint | Systolic Blood Pressure (SBP) | 1.09 mm Hg | Standard Error 0.8 |
| Duloxetine | Change From Baseline in Blood Pressure at 12 Week Endpoint | Diastolic Blood Pressure (DBP) | 0.83 mm Hg | Standard Error 0.51 |
| Placebo | Change From Baseline in Blood Pressure at 12 Week Endpoint | Systolic Blood Pressure (SBP) | -0.72 mm Hg | Standard Error 0.78 |
| Placebo | Change From Baseline in Blood Pressure at 12 Week Endpoint | Diastolic Blood Pressure (DBP) | 0.31 mm Hg | Standard Error 0.5 |
p-value: 0.08495% CI: [-0.25, 3.88]ANCOVA
p-value: 0.43495% CI: [-0.79, 1.84]ANCOVA
Secondary
Change From Baseline in Brief Pain Inventory (BPI) (Modified Short Form) at 12 Week Endpoint
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).
Time frame: Baseline, 12 weeks
Population: Number of patients with a non-missing baseline and at least one post-baseline record. Last observation carried forward.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine | 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 |
| Duloxetine | 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 |
| Duloxetine | 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 |
| Duloxetine | 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 |
| Duloxetine | 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 |
| Duloxetine | 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 |
| Duloxetine | 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 |
| Duloxetine | 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 |
| Duloxetine | 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 |
| Duloxetine | 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 |
| Duloxetine | 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 |
| Duloxetine | 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 |
| Placebo | Change From Baseline in Brief Pain Inventory (BPI) (Modified Short Form) at 12 Week Endpoint | Average Interference | -1.52 units on a scale | Standard Error 0.15 |
| Placebo | Change From Baseline in Brief Pain Inventory (BPI) (Modified Short Form) at 12 Week Endpoint | Worst Pain Severity | -1.57 units on a scale | Standard Error 0.17 |
| Placebo | Change From Baseline in Brief Pain Inventory (BPI) (Modified Short Form) at 12 Week Endpoint | Least Pain Severity | -0.96 units on a scale | Standard Error 0.14 |
| Placebo | Change From Baseline in Brief Pain Inventory (BPI) (Modified Short Form) at 12 Week Endpoint | Average Pain Severity | -1.40 units on a scale | Standard Error 0.15 |
| Placebo | Change From Baseline in Brief Pain Inventory (BPI) (Modified Short Form) at 12 Week Endpoint | Pain Right Now Severity | -1.34 units on a scale | Standard Error 0.17 |
| Placebo | Change From Baseline in Brief Pain Inventory (BPI) (Modified Short Form) at 12 Week Endpoint | General Activity Interference | -1.44 units on a scale | Standard Error 0.17 |
| Placebo | Change From Baseline in Brief Pain Inventory (BPI) (Modified Short Form) at 12 Week Endpoint | Walking Ability Interference | -1.36 units on a scale | Standard Error 0.17 |
| Placebo | Change From Baseline in Brief Pain Inventory (BPI) (Modified Short Form) at 12 Week Endpoint | Normal Work Interference | -1.60 units on a scale | Standard Error 0.17 |
| Placebo | Change From Baseline in Brief Pain Inventory (BPI) (Modified Short Form) at 12 Week Endpoint | Relations with Other People Interference | -1.22 units on a scale | Standard Error 0.16 |
| Placebo | Change From Baseline in Brief Pain Inventory (BPI) (Modified Short Form) at 12 Week Endpoint | Sleep Interference | -1.81 units on a scale | Standard Error 0.18 |
| Placebo | Change From Baseline in Brief Pain Inventory (BPI) (Modified Short Form) at 12 Week Endpoint | Enjoyment of Life Interference | -1.45 units on a scale | Standard Error 0.19 |
| Placebo | Change From Baseline in Brief Pain Inventory (BPI) (Modified Short Form) at 12 Week Endpoint | Mood Interference | -1.61 units on a scale | Standard Error 0.18 |
p-value: <0.00195% CI: [-1.19, -0.31]ANCOVA
p-value: 0.00195% CI: [-0.99, -0.24]ANCOVA
p-value: <0.00195% CI: [-1.13, -0.35]ANCOVA
p-value: <0.00195% CI: [-1.2, -0.31]ANCOVA
p-value: <0.00195% CI: [-1.39, -0.49]ANCOVA
p-value: <0.00195% CI: [-1.41, -0.49]ANCOVA
p-value: <0.00195% CI: [-1.24, -0.36]ANCOVA
p-value: <0.00195% CI: [-1.21, -0.32]ANCOVA
p-value: <0.00195% CI: [-1.38, -0.52]ANCOVA
p-value: <0.00195% CI: [-1.35, -0.39]ANCOVA
p-value: <0.00195% CI: [-1.92, -0.86]ANCOVA
p-value: <0.00195% CI: [-1.33, -0.52]ANCOVA
Secondary
Change From Baseline in Clinical Global Impressions of Severity (CGI-S) at 12 Week Endpoint
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).
Time frame: Baseline, 12 Weeks
Population: Number of patients with a non-missing baseline and at least one post-baseline record.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine | 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 |
| Placebo | Change From Baseline in Clinical Global Impressions of Severity (CGI-S) at 12 Week Endpoint | -0.71 units on a scale | Standard Error 0.07 |
p-value: <0.00195% CI: [-0.51, -0.16]ANCOVA
Secondary
Change From Baseline in Heart Rate at 12 Week Endpoint
Time frame: Baseline, 12 weeks
Population: Number of patients with a baseline and at least one post-baseline result.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine | Change From Baseline in Heart Rate at 12 Week Endpoint | 1.76 beats per minute (bpm) | Standard Error 0.5 |
| Placebo | Change From Baseline in Heart Rate at 12 Week Endpoint | -0.20 beats per minute (bpm) | Standard Error 0.49 |
p-value: 0.00395% CI: [0.67, 3.26]ANCOVA
Secondary
Change From Baseline in Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (MGH-CPFQ) Total Score at 12 Week Endpoint
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.
Time frame: Baseline, 12 weeks
Population: Number of patients with a non-missing baseline and at least one post-baseline record.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine | 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 |
| Placebo | Change From Baseline in Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (MGH-CPFQ) Total Score at 12 Week Endpoint | -3.92 units on a scale | Standard Error 0.41 |
p-value: 0.08395% CI: [-2.05, 0.13]ANCOVA
Secondary
Change From Baseline in Multidimensional Fatigue Inventory (MFI) at 12 Week Endpoint
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.
Time frame: Baseline, 12 weeks
Population: Number of patients with a non-missing baseline and at least one post-baseline record.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine | Change From Baseline in Multidimensional Fatigue Inventory (MFI) at 12 Week Endpoint | Physical Fatigue | -2.08 units on a scale | Standard Error 0.22 |
| Duloxetine | Change From Baseline in Multidimensional Fatigue Inventory (MFI) at 12 Week Endpoint | Reduced Activity | -1.46 units on a scale | Standard Error 0.24 |
| Duloxetine | Change From Baseline in Multidimensional Fatigue Inventory (MFI) at 12 Week Endpoint | Mental Fatigue | -2.01 units on a scale | Standard Error 0.23 |
| Duloxetine | Change From Baseline in Multidimensional Fatigue Inventory (MFI) at 12 Week Endpoint | Reduced Motivation | -1.66 units on a scale | Standard Error 0.22 |
| Duloxetine | Change From Baseline in Multidimensional Fatigue Inventory (MFI) at 12 Week Endpoint | General Fatigue | -2.21 units on a scale | Standard Error 0.22 |
| Placebo | Change From Baseline in Multidimensional Fatigue Inventory (MFI) at 12 Week Endpoint | Reduced Motivation | -0.72 units on a scale | Standard Error 0.21 |
| Placebo | Change From Baseline in Multidimensional Fatigue Inventory (MFI) at 12 Week Endpoint | General Fatigue | -1.38 units on a scale | Standard Error 0.22 |
| Placebo | Change From Baseline in Multidimensional Fatigue Inventory (MFI) at 12 Week Endpoint | Physical Fatigue | -1.35 units on a scale | Standard Error 0.22 |
| Placebo | Change From Baseline in Multidimensional Fatigue Inventory (MFI) at 12 Week Endpoint | Mental Fatigue | -1.09 units on a scale | Standard Error 0.23 |
| Placebo | Change From Baseline in Multidimensional Fatigue Inventory (MFI) at 12 Week Endpoint | Reduced Activity | -0.59 units on a scale | Standard Error 0.23 |
p-value: 0.00595% CI: [-1.41, -0.25]ANCOVA
p-value: 0.01395% CI: [-1.3, -0.15]ANCOVA
p-value: 0.00395% CI: [-1.52, -0.32]ANCOVA
p-value: 0.00595% CI: [-1.49, -0.26]ANCOVA
p-value: <0.00195% CI: [-1.49, -0.38]ANCOVA
Secondary
Change From Baseline in the Mood, Anxiety, Pain, Sleep, and Stiffness Likert Scale at 12 Week Endpoint
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.
Time frame: Baseline, 12 weeks
Population: Number of patients with a non-missing baseline and at least one post-baseline record.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine | 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 |
| Duloxetine | 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 |
| Duloxetine | 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 |
| Duloxetine | 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 |
| Duloxetine | 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 |
| Placebo | Change From Baseline in the Mood, Anxiety, Pain, Sleep, and Stiffness Likert Scale at 12 Week Endpoint | Stiffness | -1.67 units on a scale | Standard Error 0.17 |
| Placebo | Change From Baseline in the Mood, Anxiety, Pain, Sleep, and Stiffness Likert Scale at 12 Week Endpoint | Mood | -0.52 units on a scale | Standard Error 0.16 |
| Placebo | Change From Baseline in the Mood, Anxiety, Pain, Sleep, and Stiffness Likert Scale at 12 Week Endpoint | Anxiety | -0.58 units on a scale | Standard Error 0.16 |
| Placebo | Change From Baseline in the Mood, Anxiety, Pain, Sleep, and Stiffness Likert Scale at 12 Week Endpoint | Pain | -1.73 units on a scale | Standard Error 0.18 |
| Placebo | Change From Baseline in the Mood, Anxiety, Pain, Sleep, and Stiffness Likert Scale at 12 Week Endpoint | Sleep | -1.47 units on a scale | Standard Error 0.18 |
p-value: <0.00195% CI: [-1.18, -0.32]ANCOVA
p-value: 0.00395% CI: [-1.05, -0.22]ANCOVA
p-value: 0.00395% CI: [-1.19, -0.25]ANCOVA
p-value: 0.0595% CI: [-0.97, 0]ANCOVA
p-value: <0.00195% CI: [-1.32, -0.43]ANCOVA
Secondary
Change From Baseline in Weight at 12 Week Endpoint
Time frame: Baseline, 12 weeks
Population: Number of patients with a baseline and at least one post-baseline result.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine | Change From Baseline in Weight at 12 Week Endpoint | -0.62 kilograms (kg) | Standard Error 0.15 |
| Placebo | Change From Baseline in Weight at 12 Week Endpoint | 0.21 kilograms (kg) | Standard Error 0.14 |
p-value: <0.00195% CI: [-1.21, -0.45]ANCOVA
Secondary
Number of Patients With Columbia Suicide Severity Rating Scale (CSSR-S) Events (Behaviors, Ideations, Acts)
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.
Time frame: Baseline through 12 Weeks
Population: Number of randomized patients.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Duloxetine | Number of Patients With Columbia Suicide Severity Rating Scale (CSSR-S) Events (Behaviors, Ideations, Acts) | Suicidal Ideation | 6 participants |
| Duloxetine | Number of Patients With Columbia Suicide Severity Rating Scale (CSSR-S) Events (Behaviors, Ideations, Acts) | Suicidal Behavior | 0 participants |
| Duloxetine | Number of Patients With Columbia Suicide Severity Rating Scale (CSSR-S) Events (Behaviors, Ideations, Acts) | Suicidal Acts | 0 participants |
| Placebo | Number of Patients With Columbia Suicide Severity Rating Scale (CSSR-S) Events (Behaviors, Ideations, Acts) | Suicidal Ideation | 7 participants |
| Placebo | Number of Patients With Columbia Suicide Severity Rating Scale (CSSR-S) Events (Behaviors, Ideations, Acts) | Suicidal Behavior | 0 participants |
| Placebo | Number of Patients With Columbia Suicide Severity Rating Scale (CSSR-S) Events (Behaviors, Ideations, Acts) | Suicidal Acts | 0 participants |
p-value: 1Fisher Exact
Secondary
Number of Responders: 30% Improvement in Brief Pain Inventory Average Pain at 12 Week Endpoint
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).
Time frame: 12 Weeks
Population: Number of randomized patients with baseline and at least one post-baseline data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Duloxetine | Number of Responders: 30% Improvement in Brief Pain Inventory Average Pain at 12 Week Endpoint | 119 participants |
| Placebo | Number of Responders: 30% Improvement in Brief Pain Inventory Average Pain at 12 Week Endpoint | 88 participants |
p-value: 0.002Fisher Exact
Secondary
Number of Responders: 50% Improvement in Brief Pain Inventory Average Pain Score at 12 Week Endpoint
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).
Time frame: 12 weeks
Population: Number of randomized patients with baseline and at least one post-baseline data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Duloxetine | Number of Responders: 50% Improvement in Brief Pain Inventory Average Pain Score at 12 Week Endpoint | 83 participants |
| Placebo | Number of Responders: 50% Improvement in Brief Pain Inventory Average Pain Score at 12 Week Endpoint | 55 participants |
p-value: 0.003Fisher Exact