Osteoarthritis Knee Pain
Conditions
Brief summary
The study will test the hypothesis that, in patients with knee pain due to osteoarthritis (OA) who are taking nonsteroidal anti-inflammatory drugs (NSAIDs) but still have significant knee pain, duloxetine 60 to 120 milligrams (mg) daily for 10 weeks will provide additional reduction in pain.
Detailed description
Duloxetine has been studied in pain due to osteoarthritis (OA) in 2 previous placebo controlled clinical trials. In clinical practice, when nonsteroidal anti-inflammatory drugs (NSAIDs) are ineffective in reducing pain due to OA, clinicians often add a second agent without discontinuing NSAIDs. In this study, we will investigate whether adding duloxetine to NSAIDs provides additional pain relief and functional improvement in patients with knee pain due to OA.
Interventions
DRUGDuloxetine
30 milligrams (mg) taken by mouth, once daily for 1 week, followed by 60 to 120 mg taken by mouth, once daily for 9 weeks.
DRUGPlacebo
Taken by mouth, once daily for 10 weeks
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Present with knee pain due to osteoarthritis (OA) based on OA clinical and radiographic diagnostic criteria. * Knee Pain for \> 14 days of each month for the 3 months directly preceding study entry. * Taking nonsteroidal anti-inflammatory drugs (NSAIDs) for knee pain due to OA on most days in the 3 months immediately preceding study entry.
Exclusion criteria
* History of intolerance or nonresponsiveness to an adequate trial of duloxetine used for any indication, in the opinion of the investigator. * Previous diagnosis of psychosis, bipolar disorder, or schizoaffective disorder. * Have major depressive disorder (MDD) as determined using depression module of the Mini International Neuropsychiatric Interview (MINI). * Judged clinically by the investigator to be at suicidal risk by examination or using the Columbia Suicide Severity Rating Scale (C-SSRS). * History of substance abuse or dependence within the past year, excluding nicotine and caffeine. * Positive urine drug screen for any substance of abuse or excluded medication. * Opioid dependent in the opinion of the investigator, taking opioids more than 3 days a week, or unwilling to discontinue opioids during the study period. * Known hypersensitivity to duloxetine or its inactive ingredients. * History of intolerance or hypersensitivity to NSAIDS, Cyclooxygenase (COX-2) inhibitors, or proton pump inhibitors. * History of peptic ulcer disease, bleeding disorder, gastrointestinal bleeding, or any abnormal bleeding. * Baseline hemoglobin measurement of \<11 grams per deciliter (g/dL) for males, or \<10 g/dL for females. * Serious or unstable cardiovascular, hepatic, renal, metabolic, respiratory, or hematologic illness, symptomatic peripheral vascular disease, or any other medical or psychiatric condition that would compromise participation or be likely to lead to hospitalization or a change in medication during the course of the study. * Uncorrected thyroid disease, uncontrolled narrow-angle glaucoma, uncontrolled or poorly controlled hypertension, or history of seizures. * Active liver injury (such as hepatitis) or any degree of hepatic insufficiency (Child-Pugh Class C). * Frequent falls that could result in hospitalization or could compromise response to treatment. * Confounding painful condition that may interfere with assessment of the index knee. * Chronic widespread pain affecting all four quadrants of the body, or diagnosis of fibromyalgia. * Received intra-articular hyaluronate (Synvisc), steroids, joint lavage, or other invasive therapies to the knee in the past 6 months. * Arthroscopy of the index knee within the past year or joint replacement of the index knee at anytime. * Diagnosis of inflammatory arthritis (that is, rheumatoid arthritis, psoriatic arthritis, reactive arthritis, ankylosing spondylitis, etc.) or an autoimmune disorder (excluding inactive Hashimoto's thyroiditis). * Prior synovial fluid analysis showing a white blood cell count greater than or equal to 2000 cubic millimeters (mm\^3) that is indicative of a diagnosis other than OA, or have a history of gout or pseudogout. * Radiographic evidence of end-stage (bone on bone) OA in either knee. * Knee replacement surgery planned within the next 6 months. * Nonambulatory or requiring the use of crutches, a walker, or more than 1 cane. * Body mass index (BMI) \>40.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Weekly Mean of the 24-Hour Average Pain Score at 8 Weeks | Baseline, 8 weeks (blinded endpoint) | The weekly mean 24-hour average pain score was calculated from the participant's daily 24-hour average pain ratings using an 11-point numeric rating scale, with scores from 0 (indicating no pain) to 10 (indicating the worst possible pain). The Least Squares Mean estimates were adjusted for baseline, treatment, investigator (pooled), week, treatment\*week, and baseline\*week. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Clinical Global Impression of Severity (CGI-S) at 8 Weeks | Baseline, 8 weeks (blinded endpoint) | The CGI-S scale evaluates the severity of illness at the time of assessment. The scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). The CGI-S must be administered by a study physician in the presence of the participant or after having been in the presence of the participant. The Least Squares Mean estimates were adjusted for baseline, treatment, investigator (pooled), visit, treatment\*visit, and baseline\*visit. |
| Percentage of Participants Using Acetaminophen Weekly During the 10-Week Treatment Period | Baseline through 10 weeks (blinded endpoint) | The Least Squares (LS) Mean percentage estimates of participants using acetaminophen was determined during each week individually over the full 10-week treatment period based on participant's daily Yes/No assessments for the use of acetaminophen. The LS Mean estimates for the main effect of treatment (average weekly use) were adjusted for baseline value, treatment, investigator (pooled), week, and treatment\*week. |
| Percentage of Responders as Assessed by the Osteoarthritis Research Society International (OARSI) Response Criteria up to 8 Weeks | Up to 8 weeks (blinded endpoint) | OARSI response is composite Yes/No response assessed at 8 weeks based on decrease in 24-hour average pain ratings, range: 0 (no pain) to 10 (worst possible pain), improvement in functioning (using WOMAC physical function scores, range: 0 \[no difficulty\] to 68 \[extreme difficulty\]), and improvement in participant's impression of illness (using PGAI scores, range: 0 to 10; 10=greatest severity). OARSI responder=large response in pain or function components (50% relative and 20% absolute improvement), or moderate response (20% relative and 10% absolute improvement) in 2 of 3 components. |
| Percentage of Participants Who Achieved a 30 Percent or 50 Percent Reduction in the Weekly Mean of the 24-Hour Average Pain Score up to 8 Weeks | Up to 8 weeks (blinded endpoint) | Response is a dichotomous outcome (Yes/No) indicating at least 30% (or 50%) reduction from baseline to endpoint for the weekly mean of the 24-hour average pain ratings. The weekly mean 24-hour average pain score was calculated from the participant's daily 24-hour average pain rating assessed on an 11-point numeric rating scale, with scores from 0 (no pain) to 10 (worst possible pain). |
| Percentage of Participants Who Achieved a 30 Percent or 50 Percent Reduction in the Brief Pain Inventory-Severity (BPI-S) Average Pain Score up to 8 Weeks | Up to 8 weeks (blinded endpoint) | Response is a dichotomous outcome (Yes/No) indicating at least 30% (or 50%) reduction from baseline to endpoint for BPI-S average pain rating. The BPI-S self-reported scale that measures the severity of pain based on the average pain experienced over the past 24 hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). |
| Percentage of Participants Who Discontinued Due to an Adverse Event During the 10-Week Treatment Period | Baseline through 10 weeks | — |
| Patient Global Impression of Improvement (PGI-I) at 8 Weeks | 8 weeks (blinded endpoint) | A scale that measures the participant's perception of improvement at the time of assessment compared with the start of treatment. The score ranges from 1 (very much better) to 7 (very much worse). The Least Squares Mean estimates were adjusted for baseline value of Patient Global Impression of Severity (PGI-S), treatment, investigator (pooled), visit, and treatment\*visit. The PGI-S measures participant's perception of severity of illness at the time of assessment. Scores range from 1 (normal, not at all ill) to 7 (extremely ill). |
| Change From Baseline in the Western Ontario and McMaster Universities Index of Osteoarthritis (WOMAC) Pain, Stiffness, and Physical Function Subscale Scores at 8 Weeks | Baseline, 8 weeks (blinded endpoint) | Self-administered questionnaire captures elements of pain, stiffness, and physical disability in participants with osteoarthritis of the knee and/or hip. Index has 24 questions (5 on pain, 2 on stiffness, 17 on physical function). Each question uses a 5-point numeric rating scale ranging from 0 (none) to 4 (extreme). Pain scores range: 0 to 20. Stiffness scores range: 0 to 8. Physical function scores range: 0 to 68. Higher scores=greater impairment. Least Squares Mean estimates were adjusted for baseline value, treatment, investigator (pooled), visit, treatment\*visit, and baseline value\*visit. |
| Change From Baseline in the Weekly Mean of the 24-Hour Night Pain and Worst Pain Scores at 8 Weeks | Baseline, 8 weeks (blinded endpoint) | Weekly mean 24-hour night pain and worst pain values are calculated from the participant's daily assessments of pain at night and worst pain during the previous 24 hours on an 11-point numeric rating scale, with scores from 0 (indicating no pain) to 10 (indicating the worst possible pain). The Least Squares Mean estimates were adjusted for baseline value, treatment, investigator (pooled), week, treatment\*week, and baseline\*week. |
| Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) Scores at 8 Weeks | Baseline, 8 weeks (blinded endpoint) | Measures pain severity and pain interference with function. Severity scores: 0 (no pain) to 10 (severe pain) on each question. Interference scores: 0 (does not interfere) to 10 (completely interferes) on each question assessing interference of pain in past 24 hours for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. Mean interference is the average across the 7 interference items. The Least Squares Mean estimates were adjusted for baseline value, treatment, investigator (pooled), visit, treatment\*visit, and baseline\*visit. |
| Change From Baseline in the Patient Global Assessment of Illness (PGAI) at 8 Weeks | Baseline, 8 weeks (blinded endpoint) | The PGAI is a participant-rated measure of the severity of osteoarthritis (OA) of the knee the participant has experienced in the past week as indicated on an 11-point numeric rating scale, with scores ranging from 0 to 10, where greater numbers reflect greater severity. The Least Squares Mean estimates were adjusted for baseline value, treatment, investigator (pooled), visit, treatment\*visit, and baseline\*visit. |
| Change From Baseline in the Profile of Mood States-Brief Form (BPOMS) Total and Subscale Scores at 8 Weeks | Baseline, 8 weeks (blinded endpoint) | 30-item BPOMS measures positive and negative aspects of mood states (item score: 0=not at all to 4=extremely). 5 negative factors: tension-anxiety, depression-dejection, anger-hostility, fatigue-inertia, confusion-bewilderment; 1 positive factor: vigor-activity. Factor scores range: 0 to 20; high scores=negative mood (positive mood for vigor). Total score=sum of 5 negative factor scores minus vigor score; range: -20=least disturbed to 100=most disturbed. Least Squares Mean estimates adjusted for baseline value, treatment, investigator (pooled), visit, treatment\*visit, and baseline value\*visit. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Abnormal Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) up to 10 Weeks | Up to 10 weeks | Abnormal DPB (diastolic hypertension) is defined as sitting DBP ≥ 90 mm Hg that is also ≥ 10 mm Hg increase from baseline that is observed at last visit if highest baseline DBP \< 90 mm Hg. Abnormal SBP (systolic hypertension) is defined as sitting SBP ≥ 140 mm Hg that is also ≥ 10 mm Hg increase from baseline that is observed at last visit if highest baseline SBP \< 140 mm Hg. |
| Percentage of Participants With Abnormal Pulse Rate up to 10 Weeks | Up to 10 weeks | Abnormal pulse rate (tachycardia) is defined as a sitting heart rate (HR) ≥ 100 beats per minute (bpm) that is also ≥ 10 bpm compared to baseline, at last visit if highest baseline HR \< 100 bpm. |
| Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | Up to 10 weeks | REU captures information regarding the participant's work status and/or health care utilization. Investigators gather information from medical records, psychiatric history, and direct questioning of the participant and his or her family to complete the questionnaire. Responses to each item, comparing baseline to endpoint, are characterized as Better, Same, or Worse. Better: an increase in time spent working/volunteering/holding a job, decrease in number of health care visits; Same: no change in time spent working/volunteering/holding a job, no change in number of health care visits; Worse: decrease in time spent working/volunteering/holding a job, increase in number of health care visits. |
| Percentage of Participants With Abnormal High Hemoglobin A1c (HbA1c) up to 10 Weeks | Up to 10 weeks | Abnormal high HbA1c is defined as a post-baseline HbA1c \> 6.1% if baseline HbA1c ≤ 6.1% for lab samples obtained before November 17, 2010 and post-baseline HbA1c \> 6.4% if baseline HbA1c ≤ 6.4% for lab samples obtained November 17, 2010 and beyond. |
| Percentage of Participants With Abnormal Weight Gain and Weight Loss up to 10 Weeks | Up to 10 weeks | Abnormal weight gain (potentially clinically significant \[PCS\] weight gain) is defined as weight gain at last visit ≥ 7% of the baseline weight. Abnormal weight loss (PCS weight loss) is defined as weight loss at last visit ≥ 7% of the baseline weight. |
Countries
Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo by mouth, once daily for 10 weeks. | 260 |
| Duloxetine Participants initially received 30 milligrams (mg) duloxetine by mouth, once daily for 1 week, followed by 60 mg by mouth, once daily thereafter. At end of 3 weeks, participants with a weekly mean 24-hour average pain value ≥4 in week preceding their visit had their dose escalated up to 120 mg by mouth, once daily until Week 10. | 264 |
| Total | 524 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 23 | 40 |
| Overall Study | Entry Criteria Not Met | 1 | 4 |
| Overall Study | Lack of Efficacy | 8 | 2 |
| Overall Study | Lost to Follow-up | 5 | 3 |
| Overall Study | Physician Decision | 3 | 1 |
| Overall Study | Protocol Violation | 5 | 8 |
| Overall Study | Sponsor Decision | 6 | 7 |
| Overall Study | Withdrawal by Subject | 10 | 10 |
Baseline characteristics
| Characteristic | Total | Duloxetine | Placebo |
|---|---|---|---|
| Age Continuous | 60.98 years STANDARD_DEVIATION 9.22 | 61.63 years STANDARD_DEVIATION 9.24 | 60.32 years STANDARD_DEVIATION 9.17 |
| Brief Pain Inventory-Severity (BPI-S) Average Pain | 6.16 units on a scale STANDARD_DEVIATION 1.54 | 6.09 units on a scale STANDARD_DEVIATION 1.58 | 6.24 units on a scale STANDARD_DEVIATION 1.51 |
| Duration of Osteoarthritis (OA) Pain | 9.49 years STANDARD_DEVIATION 8.9 | 9.79 years STANDARD_DEVIATION 8.88 | 9.19 years STANDARD_DEVIATION 8.92 |
| Patient Global Assessment of Illness (PGAI) | 6.94 units on a scale STANDARD_DEVIATION 1.49 | 6.93 units on a scale STANDARD_DEVIATION 1.49 | 6.95 units on a scale STANDARD_DEVIATION 1.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 4 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 84 Participants | 38 Participants | 46 Participants |
| Race (NIH/OMB) More than one race | 8 Participants | 6 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 424 Participants | 218 Participants | 206 Participants |
| Region of Enrollment United States | 524 participants | 264 participants | 260 participants |
| Sex: Female, Male Female | 299 Participants | 152 Participants | 147 Participants |
| Sex: Female, Male Male | 225 Participants | 112 Participants | 113 Participants |
| Weekly 24-Hour Average Pain Rating | 6.32 units on a scale STANDARD_DEVIATION 1.41 | 6.27 units on a scale STANDARD_DEVIATION 1.41 | 6.36 units on a scale STANDARD_DEVIATION 1.41 |
| Weight | 90.59 kilograms (kg) STANDARD_DEVIATION 17.8 | 90.41 kilograms (kg) STANDARD_DEVIATION 18.13 | 90.78 kilograms (kg) STANDARD_DEVIATION 17.49 |
| Western Ontario and McMaster Universities Index of Osteoarthritis Physical Function Score | 37.45 units on a scale STANDARD_DEVIATION 9.74 | 37.40 units on a scale STANDARD_DEVIATION 10.1 | 37.51 units on a scale STANDARD_DEVIATION 9.39 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 129 / 260 | 167 / 264 |
| serious Total, serious adverse events | 3 / 260 | 5 / 264 |
Outcome results
Primary
Change From Baseline in the Weekly Mean of the 24-Hour Average Pain Score at 8 Weeks
The weekly mean 24-hour average pain score was calculated from the participant's daily 24-hour average pain ratings using an 11-point numeric rating scale, with scores from 0 (indicating no pain) to 10 (indicating the worst possible pain). The Least Squares Mean estimates were adjusted for baseline, treatment, investigator (pooled), week, treatment\*week, and baseline\*week.
Time frame: Baseline, 8 weeks (blinded endpoint)
Population: Modified intent to treat (mITT) population: ITT participants with a baseline and at least 1 post-baseline weekly mean 24-hour average pain value were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Weekly Mean of the 24-Hour Average Pain Score at 8 Weeks | -1.55 units on a scale | Standard Error 0.11 |
| Duloxetine | Change From Baseline in the Weekly Mean of the 24-Hour Average Pain Score at 8 Weeks | -2.46 units on a scale | Standard Error 0.11 |
Comparison: Using a 1:1 ratio of allocation to treatment, a 2-tailed 0.05 level of significance and 80% power, 253 participants per arm had been estimated to be adequate to assess an effect size of 0.25, based on a 2-sample Student's t-test. This derived estimate was increased slightly to 261 participants per arm to account for extremely early discontinuation that would have led to exclusion from the efficacy analysis in a small number of participants (approximately 3%).p-value: <0.001Mixed Models Analysis
Secondary
Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) Scores at 8 Weeks
Measures pain severity and pain interference with function. Severity scores: 0 (no pain) to 10 (severe pain) on each question. Interference scores: 0 (does not interfere) to 10 (completely interferes) on each question assessing interference of pain in past 24 hours for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. Mean interference is the average across the 7 interference items. The Least Squares Mean estimates were adjusted for baseline value, treatment, investigator (pooled), visit, treatment\*visit, and baseline\*visit.
Time frame: Baseline, 8 weeks (blinded endpoint)
Population: Modified intent to treat (mITT) population: ITT participants with a baseline and at least 1 post-baseline BPI-S/BPI-I value were included in the analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) Scores at 8 Weeks | BPI-S for Worst Pain | -1.87 units on a scale | Standard Error 0.17 |
| Placebo | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) Scores at 8 Weeks | BPI-S for Least Pain | -1.44 units on a scale | Standard Error 0.14 |
| Placebo | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) Scores at 8 Weeks | BPI-S for Average Pain | -1.78 units on a scale | Standard Error 0.15 |
| Placebo | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) Scores at 8 Weeks | BPI-S for Pain Right Now | -2.03 units on a scale | Standard Error 0.16 |
| Placebo | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) Scores at 8 Weeks | BPI-I for General Activity | -1.79 units on a scale | Standard Error 0.17 |
| Placebo | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) Scores at 8 Weeks | BPI-I for Mood | -1.80 units on a scale | Standard Error 0.15 |
| Placebo | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) Scores at 8 Weeks | BPI-I for Walking Ability | -1.85 units on a scale | Standard Error 0.17 |
| Placebo | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) Scores at 8 Weeks | BPI-I for Normal Work | -1.92 units on a scale | Standard Error 0.17 |
| Placebo | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) Scores at 8 Weeks | BPI-I for Relations with Others (n=255, 258) | -1.25 units on a scale | Standard Error 0.14 |
| Placebo | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) Scores at 8 Weeks | BPI-I for Sleep | -2.01 units on a scale | Standard Error 0.14 |
| Placebo | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) Scores at 8 Weeks | BPI-I for Enjoyment of Life | -1.89 units on a scale | Standard Error 0.17 |
| Placebo | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) Scores at 8 Weeks | BPI-I for Mean Interference Score | -1.77 units on a scale | Standard Error 0.14 |
| Duloxetine | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) Scores at 8 Weeks | BPI-I for Enjoyment of Life | -2.66 units on a scale | Standard Error 0.17 |
| Duloxetine | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) Scores at 8 Weeks | BPI-S for Worst Pain | -2.94 units on a scale | Standard Error 0.17 |
| Duloxetine | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) Scores at 8 Weeks | BPI-I for Walking Ability | -2.80 units on a scale | Standard Error 0.17 |
| Duloxetine | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) Scores at 8 Weeks | BPI-S for Least Pain | -2.14 units on a scale | Standard Error 0.14 |
| Duloxetine | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) Scores at 8 Weeks | BPI-I for Sleep | -2.69 units on a scale | Standard Error 0.14 |
| Duloxetine | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) Scores at 8 Weeks | BPI-S for Average Pain | -2.73 units on a scale | Standard Error 0.15 |
| Duloxetine | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) Scores at 8 Weeks | BPI-I for Normal Work | -2.77 units on a scale | Standard Error 0.17 |
| Duloxetine | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) Scores at 8 Weeks | BPI-S for Pain Right Now | -2.74 units on a scale | Standard Error 0.16 |
| Duloxetine | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) Scores at 8 Weeks | BPI-I for Mean Interference Score | -2.60 units on a scale | Standard Error 0.14 |
| Duloxetine | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) Scores at 8 Weeks | BPI-I for General Activity | -2.76 units on a scale | Standard Error 0.16 |
| Duloxetine | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) Scores at 8 Weeks | BPI-I for Relations with Others (n=255, 258) | -1.94 units on a scale | Standard Error 0.14 |
| Duloxetine | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) Scores at 8 Weeks | BPI-I for Mood | -2.52 units on a scale | Standard Error 0.15 |
p-value: <0.001Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
Secondary
Change From Baseline in the Clinical Global Impression of Severity (CGI-S) at 8 Weeks
The CGI-S scale evaluates the severity of illness at the time of assessment. The scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). The CGI-S must be administered by a study physician in the presence of the participant or after having been in the presence of the participant. The Least Squares Mean estimates were adjusted for baseline, treatment, investigator (pooled), visit, treatment\*visit, and baseline\*visit.
Time frame: Baseline, 8 weeks (blinded endpoint)
Population: Modified intent to treat (mITT) population: ITT participants with a baseline and at least 1 post-baseline CGI-S value were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Clinical Global Impression of Severity (CGI-S) at 8 Weeks | -0.80 units on a scale | Standard Error 0.07 |
| Duloxetine | Change From Baseline in the Clinical Global Impression of Severity (CGI-S) at 8 Weeks | -1.16 units on a scale | Standard Error 0.07 |
p-value: <0.001Mixed Models Analysis
Secondary
Change From Baseline in the Patient Global Assessment of Illness (PGAI) at 8 Weeks
The PGAI is a participant-rated measure of the severity of osteoarthritis (OA) of the knee the participant has experienced in the past week as indicated on an 11-point numeric rating scale, with scores ranging from 0 to 10, where greater numbers reflect greater severity. The Least Squares Mean estimates were adjusted for baseline value, treatment, investigator (pooled), visit, treatment\*visit, and baseline\*visit.
Time frame: Baseline, 8 weeks (blinded endpoint)
Population: Modified intent to treat (mITT) population: ITT participants with a baseline and at least 1 post-baseline PGAI value were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Patient Global Assessment of Illness (PGAI) at 8 Weeks | -1.77 units on a scale | Standard Error 0.17 |
| Duloxetine | Change From Baseline in the Patient Global Assessment of Illness (PGAI) at 8 Weeks | -2.95 units on a scale | Standard Error 0.17 |
p-value: <0.001Mixed Models Analysis
Secondary
Change From Baseline in the Profile of Mood States-Brief Form (BPOMS) Total and Subscale Scores at 8 Weeks
30-item BPOMS measures positive and negative aspects of mood states (item score: 0=not at all to 4=extremely). 5 negative factors: tension-anxiety, depression-dejection, anger-hostility, fatigue-inertia, confusion-bewilderment; 1 positive factor: vigor-activity. Factor scores range: 0 to 20; high scores=negative mood (positive mood for vigor). Total score=sum of 5 negative factor scores minus vigor score; range: -20=least disturbed to 100=most disturbed. Least Squares Mean estimates adjusted for baseline value, treatment, investigator (pooled), visit, treatment\*visit, and baseline value\*visit.
Time frame: Baseline, 8 weeks (blinded endpoint)
Population: Modified intent to treat (mITT) population: ITT participants with a baseline and at least 1 post-baseline BPOMS value were included in the analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the Profile of Mood States-Brief Form (BPOMS) Total and Subscale Scores at 8 Weeks | BPOMS Depression-Dejection Score | -0.51 units on a scale | Standard Error 0.21 |
| Placebo | Change From Baseline in the Profile of Mood States-Brief Form (BPOMS) Total and Subscale Scores at 8 Weeks | BPOMS Vigor-Activity Score | -0.34 units on a scale | Standard Error 0.33 |
| Placebo | Change From Baseline in the Profile of Mood States-Brief Form (BPOMS) Total and Subscale Scores at 8 Weeks | BPOMS Tension-Anxiety Score | -0.90 units on a scale | Standard Error 0.21 |
| Placebo | Change From Baseline in the Profile of Mood States-Brief Form (BPOMS) Total and Subscale Scores at 8 Weeks | BPOMS Fatigue-Inertia Score | -1.40 units on a scale | Standard Error 0.3 |
| Placebo | Change From Baseline in the Profile of Mood States-Brief Form (BPOMS) Total and Subscale Scores at 8 Weeks | BPOMS Anger-Hostility Score | -0.63 units on a scale | Standard Error 0.21 |
| Placebo | Change From Baseline in the Profile of Mood States-Brief Form (BPOMS) Total and Subscale Scores at 8 Weeks | BPOMS Confusion-Bewilderment Score | -0.29 units on a scale | Standard Error 0.17 |
| Placebo | Change From Baseline in the Profile of Mood States-Brief Form (BPOMS) Total and Subscale Scores at 8 Weeks | BPOMS Total Score | -4.15 units on a scale | Standard Error 0.89 |
| Duloxetine | Change From Baseline in the Profile of Mood States-Brief Form (BPOMS) Total and Subscale Scores at 8 Weeks | BPOMS Confusion-Bewilderment Score | -0.32 units on a scale | Standard Error 0.17 |
| Duloxetine | Change From Baseline in the Profile of Mood States-Brief Form (BPOMS) Total and Subscale Scores at 8 Weeks | BPOMS Total Score | -4.98 units on a scale | Standard Error 0.88 |
| Duloxetine | Change From Baseline in the Profile of Mood States-Brief Form (BPOMS) Total and Subscale Scores at 8 Weeks | BPOMS Tension-Anxiety Score | -1.17 units on a scale | Standard Error 0.2 |
| Duloxetine | Change From Baseline in the Profile of Mood States-Brief Form (BPOMS) Total and Subscale Scores at 8 Weeks | BPOMS Depression-Dejection Score | -0.85 units on a scale | Standard Error 0.2 |
| Duloxetine | Change From Baseline in the Profile of Mood States-Brief Form (BPOMS) Total and Subscale Scores at 8 Weeks | BPOMS Anger-Hostility Score | -1.15 units on a scale | Standard Error 0.21 |
| Duloxetine | Change From Baseline in the Profile of Mood States-Brief Form (BPOMS) Total and Subscale Scores at 8 Weeks | BPOMS Vigor-Activity Score | 0.04 units on a scale | Standard Error 0.32 |
| Duloxetine | Change From Baseline in the Profile of Mood States-Brief Form (BPOMS) Total and Subscale Scores at 8 Weeks | BPOMS Fatigue-Inertia Score | -1.47 units on a scale | Standard Error 0.29 |
p-value: 0.449Mixed Models Analysis
p-value: 0.265Mixed Models Analysis
p-value: 0.18Mixed Models Analysis
p-value: 0.041Mixed Models Analysis
p-value: 0.356Mixed Models Analysis
p-value: 0.862Mixed Models Analysis
p-value: 0.883Mixed Models Analysis
Secondary
Change From Baseline in the Weekly Mean of the 24-Hour Night Pain and Worst Pain Scores at 8 Weeks
Weekly mean 24-hour night pain and worst pain values are calculated from the participant's daily assessments of pain at night and worst pain during the previous 24 hours on an 11-point numeric rating scale, with scores from 0 (indicating no pain) to 10 (indicating the worst possible pain). The Least Squares Mean estimates were adjusted for baseline value, treatment, investigator (pooled), week, treatment\*week, and baseline\*week.
Time frame: Baseline, 8 weeks (blinded endpoint)
Population: Modified intent to treat (mITT) population: ITT participants with a baseline night/worst pain value and at least 1 post-baseline weekly mean 24-hour night/worst pain value were included in the analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the Weekly Mean of the 24-Hour Night Pain and Worst Pain Scores at 8 Weeks | Worst Pain Intensity | -1.58 units on a scale | Standard Error 0.13 |
| Placebo | Change From Baseline in the Weekly Mean of the 24-Hour Night Pain and Worst Pain Scores at 8 Weeks | Night Pain Intensity | -1.46 units on a scale | Standard Error 0.11 |
| Duloxetine | Change From Baseline in the Weekly Mean of the 24-Hour Night Pain and Worst Pain Scores at 8 Weeks | Night Pain Intensity | -2.26 units on a scale | Standard Error 0.11 |
| Duloxetine | Change From Baseline in the Weekly Mean of the 24-Hour Night Pain and Worst Pain Scores at 8 Weeks | Worst Pain Intensity | -2.61 units on a scale | Standard Error 0.13 |
p-value: <0.001Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
Secondary
Change From Baseline in the Western Ontario and McMaster Universities Index of Osteoarthritis (WOMAC) Pain, Stiffness, and Physical Function Subscale Scores at 8 Weeks
Self-administered questionnaire captures elements of pain, stiffness, and physical disability in participants with osteoarthritis of the knee and/or hip. Index has 24 questions (5 on pain, 2 on stiffness, 17 on physical function). Each question uses a 5-point numeric rating scale ranging from 0 (none) to 4 (extreme). Pain scores range: 0 to 20. Stiffness scores range: 0 to 8. Physical function scores range: 0 to 68. Higher scores=greater impairment. Least Squares Mean estimates were adjusted for baseline value, treatment, investigator (pooled), visit, treatment\*visit, and baseline value\*visit.
Time frame: Baseline, 8 weeks (blinded endpoint)
Population: Modified intent to treat (mITT) population: ITT participants with a baseline and at least 1 post-baseline WOMAC value were included in the analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the Western Ontario and McMaster Universities Index of Osteoarthritis (WOMAC) Pain, Stiffness, and Physical Function Subscale Scores at 8 Weeks | WOMAC Physical Disability Score (n=253, 251) | -10.25 units on a scale | Standard Error 0.82 |
| Placebo | Change From Baseline in the Western Ontario and McMaster Universities Index of Osteoarthritis (WOMAC) Pain, Stiffness, and Physical Function Subscale Scores at 8 Weeks | WOMAC Pain Score | -3.13 units on a scale | Standard Error 0.24 |
| Placebo | Change From Baseline in the Western Ontario and McMaster Universities Index of Osteoarthritis (WOMAC) Pain, Stiffness, and Physical Function Subscale Scores at 8 Weeks | WOMAC Stiffness Score | -1.45 units on a scale | Standard Error 0.12 |
| Duloxetine | Change From Baseline in the Western Ontario and McMaster Universities Index of Osteoarthritis (WOMAC) Pain, Stiffness, and Physical Function Subscale Scores at 8 Weeks | WOMAC Physical Disability Score (n=253, 251) | -15.09 units on a scale | Standard Error 0.81 |
| Duloxetine | Change From Baseline in the Western Ontario and McMaster Universities Index of Osteoarthritis (WOMAC) Pain, Stiffness, and Physical Function Subscale Scores at 8 Weeks | WOMAC Pain Score | -4.41 units on a scale | Standard Error 0.23 |
| Duloxetine | Change From Baseline in the Western Ontario and McMaster Universities Index of Osteoarthritis (WOMAC) Pain, Stiffness, and Physical Function Subscale Scores at 8 Weeks | WOMAC Stiffness Score | -1.88 units on a scale | Standard Error 0.11 |
p-value: <0.001Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
p-value: 0.004Mixed Models Analysis
Secondary
Patient Global Impression of Improvement (PGI-I) at 8 Weeks
A scale that measures the participant's perception of improvement at the time of assessment compared with the start of treatment. The score ranges from 1 (very much better) to 7 (very much worse). The Least Squares Mean estimates were adjusted for baseline value of Patient Global Impression of Severity (PGI-S), treatment, investigator (pooled), visit, and treatment\*visit. The PGI-S measures participant's perception of severity of illness at the time of assessment. Scores range from 1 (normal, not at all ill) to 7 (extremely ill).
Time frame: 8 weeks (blinded endpoint)
Population: Modified intent to treat (mITT) population: ITT participants with a baseline PGI-S rating and at least 1 post-baseline PGI-I rating were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Patient Global Impression of Improvement (PGI-I) at 8 Weeks | 2.93 units on a scale | Standard Error 0.09 |
| Duloxetine | Patient Global Impression of Improvement (PGI-I) at 8 Weeks | 2.33 units on a scale | Standard Error 0.09 |
p-value: <0.001Mixed Models Analysis
Secondary
Percentage of Participants Using Acetaminophen Weekly During the 10-Week Treatment Period
The Least Squares (LS) Mean percentage estimates of participants using acetaminophen was determined during each week individually over the full 10-week treatment period based on participant's daily Yes/No assessments for the use of acetaminophen. The LS Mean estimates for the main effect of treatment (average weekly use) were adjusted for baseline value, treatment, investigator (pooled), week, and treatment\*week.
Time frame: Baseline through 10 weeks (blinded endpoint)
Population: Modified intent to treat (mITT) population: ITT participants with a baseline and at least 1 post-baseline weekly acetaminophen use value were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percentage of Participants Using Acetaminophen Weekly During the 10-Week Treatment Period | 26 percentage of participants | Standard Error 2 |
| Duloxetine | Percentage of Participants Using Acetaminophen Weekly During the 10-Week Treatment Period | 22 percentage of participants | Standard Error 2 |
p-value: 0.083Mixed Models Analysis
Secondary
Percentage of Participants Who Achieved a 30 Percent or 50 Percent Reduction in the Brief Pain Inventory-Severity (BPI-S) Average Pain Score up to 8 Weeks
Response is a dichotomous outcome (Yes/No) indicating at least 30% (or 50%) reduction from baseline to endpoint for BPI-S average pain rating. The BPI-S self-reported scale that measures the severity of pain based on the average pain experienced over the past 24 hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine).
Time frame: Up to 8 weeks (blinded endpoint)
Population: Modified intent to treat (mITT) population: ITT participants with a baseline and at least 1 post-baseline BPI-S average pain value, last-observation-carried forward (LOCF) were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants Who Achieved a 30 Percent or 50 Percent Reduction in the Brief Pain Inventory-Severity (BPI-S) Average Pain Score up to 8 Weeks | 30% Response (LOCF) based on BPI-S Average Pain | 34.0 percentage of participants |
| Placebo | Percentage of Participants Who Achieved a 30 Percent or 50 Percent Reduction in the Brief Pain Inventory-Severity (BPI-S) Average Pain Score up to 8 Weeks | 50% Response (LOCF) based on BPI-S Average Pain | 21.1 percentage of participants |
| Duloxetine | Percentage of Participants Who Achieved a 30 Percent or 50 Percent Reduction in the Brief Pain Inventory-Severity (BPI-S) Average Pain Score up to 8 Weeks | 30% Response (LOCF) based on BPI-S Average Pain | 58.1 percentage of participants |
| Duloxetine | Percentage of Participants Who Achieved a 30 Percent or 50 Percent Reduction in the Brief Pain Inventory-Severity (BPI-S) Average Pain Score up to 8 Weeks | 50% Response (LOCF) based on BPI-S Average Pain | 45.7 percentage of participants |
p-value: <0.001Fisher Exact
p-value: <0.001Fisher Exact
Secondary
Percentage of Participants Who Achieved a 30 Percent or 50 Percent Reduction in the Weekly Mean of the 24-Hour Average Pain Score up to 8 Weeks
Response is a dichotomous outcome (Yes/No) indicating at least 30% (or 50%) reduction from baseline to endpoint for the weekly mean of the 24-hour average pain ratings. The weekly mean 24-hour average pain score was calculated from the participant's daily 24-hour average pain rating assessed on an 11-point numeric rating scale, with scores from 0 (no pain) to 10 (worst possible pain).
Time frame: Up to 8 weeks (blinded endpoint)
Population: Modified intent to treat (mITT) population: ITT participants with a baseline and at least 1 post-baseline weekly mean of the 24-hour average pain score value, last-observation-carried forward (LOCF) were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants Who Achieved a 30 Percent or 50 Percent Reduction in the Weekly Mean of the 24-Hour Average Pain Score up to 8 Weeks | 30% Response (LOCF) based on 24-Hour Average Pain | 33.7 percentage of participants |
| Placebo | Percentage of Participants Who Achieved a 30 Percent or 50 Percent Reduction in the Weekly Mean of the 24-Hour Average Pain Score up to 8 Weeks | 50% Response (LOCF) based on 24-Hour Average Pain | 16.1 percentage of participants |
| Duloxetine | Percentage of Participants Who Achieved a 30 Percent or 50 Percent Reduction in the Weekly Mean of the 24-Hour Average Pain Score up to 8 Weeks | 30% Response (LOCF) based on 24-Hour Average Pain | 53.7 percentage of participants |
| Duloxetine | Percentage of Participants Who Achieved a 30 Percent or 50 Percent Reduction in the Weekly Mean of the 24-Hour Average Pain Score up to 8 Weeks | 50% Response (LOCF) based on 24-Hour Average Pain | 35.5 percentage of participants |
p-value: <0.001Fisher Exact
p-value: <0.001Fisher Exact
Secondary
Percentage of Participants Who Discontinued Due to an Adverse Event During the 10-Week Treatment Period
Time frame: Baseline through 10 weeks
Population: All randomized participants were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Discontinued Due to an Adverse Event During the 10-Week Treatment Period | 8.8 percentage of participants |
| Duloxetine | Percentage of Participants Who Discontinued Due to an Adverse Event During the 10-Week Treatment Period | 15.2 percentage of participants |
p-value: 0.031Fisher Exact
Secondary
Percentage of Responders as Assessed by the Osteoarthritis Research Society International (OARSI) Response Criteria up to 8 Weeks
OARSI response is composite Yes/No response assessed at 8 weeks based on decrease in 24-hour average pain ratings, range: 0 (no pain) to 10 (worst possible pain), improvement in functioning (using WOMAC physical function scores, range: 0 \[no difficulty\] to 68 \[extreme difficulty\]), and improvement in participant's impression of illness (using PGAI scores, range: 0 to 10; 10=greatest severity). OARSI responder=large response in pain or function components (50% relative and 20% absolute improvement), or moderate response (20% relative and 10% absolute improvement) in 2 of 3 components.
Time frame: Up to 8 weeks (blinded endpoint)
Population: Modified intent to treat (mITT) population: ITT participants with a baseline and at least 1 post-baseline OARSI response value, last-observation-carried forward (LOCF) based on values of each of the 3 components listed in the outcome measure description were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Responders as Assessed by the Osteoarthritis Research Society International (OARSI) Response Criteria up to 8 Weeks | 48.3 percentage of responders |
| Duloxetine | Percentage of Responders as Assessed by the Osteoarthritis Research Society International (OARSI) Response Criteria up to 8 Weeks | 69.6 percentage of responders |
p-value: <0.001Fisher Exact
Other Pre-specified
Percentage of Participants With Abnormal Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) up to 10 Weeks
Abnormal DPB (diastolic hypertension) is defined as sitting DBP ≥ 90 mm Hg that is also ≥ 10 mm Hg increase from baseline that is observed at last visit if highest baseline DBP \< 90 mm Hg. Abnormal SBP (systolic hypertension) is defined as sitting SBP ≥ 140 mm Hg that is also ≥ 10 mm Hg increase from baseline that is observed at last visit if highest baseline SBP \< 140 mm Hg.
Time frame: Up to 10 weeks
Population: Participants with a normal baseline and at least 1 post-baseline DBP and SBP value, last-observation-carried forward (LOCF) were included in the analysis. Participants with a normal baseline value and a nonmissing endpoint value for the variable of interest were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Abnormal Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) up to 10 Weeks | Diastolic Hypertension | 1.0 percentage of participants |
| Placebo | Percentage of Participants With Abnormal Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) up to 10 Weeks | Systolic Hypertension (N=170, 171) | 4.7 percentage of participants |
| Duloxetine | Percentage of Participants With Abnormal Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) up to 10 Weeks | Diastolic Hypertension | 4.2 percentage of participants |
| Duloxetine | Percentage of Participants With Abnormal Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) up to 10 Weeks | Systolic Hypertension (N=170, 171) | 12.3 percentage of participants |
p-value: 0.063Fisher Exact
p-value: 0.018Fisher Exact
Other Pre-specified
Percentage of Participants With Abnormal High Hemoglobin A1c (HbA1c) up to 10 Weeks
Abnormal high HbA1c is defined as a post-baseline HbA1c \> 6.1% if baseline HbA1c ≤ 6.1% for lab samples obtained before November 17, 2010 and post-baseline HbA1c \> 6.4% if baseline HbA1c ≤ 6.4% for lab samples obtained November 17, 2010 and beyond.
Time frame: Up to 10 weeks
Population: Number of participants with a normal baseline and at least 1 post-baseline abnormal HbA1C value, last-observation-carried forward (LOCF) were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Abnormal High Hemoglobin A1c (HbA1c) up to 10 Weeks | 5.7 percentage of participants |
| Duloxetine | Percentage of Participants With Abnormal High Hemoglobin A1c (HbA1c) up to 10 Weeks | 1.0 percentage of participants |
p-value: 0.012Fisher Exact
Other Pre-specified
Percentage of Participants With Abnormal Pulse Rate up to 10 Weeks
Abnormal pulse rate (tachycardia) is defined as a sitting heart rate (HR) ≥ 100 beats per minute (bpm) that is also ≥ 10 bpm compared to baseline, at last visit if highest baseline HR \< 100 bpm.
Time frame: Up to 10 weeks
Population: Participants with a normal baseline and at least 1 post-baseline pulse rate value, last-observation-carried forward (LOCF) were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Abnormal Pulse Rate up to 10 Weeks | 0.0 percentage of participants |
| Duloxetine | Percentage of Participants With Abnormal Pulse Rate up to 10 Weeks | 1.1 percentage of participants |
p-value: 0.249Fisher Exact
Other Pre-specified
Percentage of Participants With Abnormal Weight Gain and Weight Loss up to 10 Weeks
Abnormal weight gain (potentially clinically significant \[PCS\] weight gain) is defined as weight gain at last visit ≥ 7% of the baseline weight. Abnormal weight loss (PCS weight loss) is defined as weight loss at last visit ≥ 7% of the baseline weight.
Time frame: Up to 10 weeks
Population: Participants with a baseline and at least 1 post-baseline weight value, last-observation-carried forward (LOCF) were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Abnormal Weight Gain and Weight Loss up to 10 Weeks | PCS Weight Gain | 1.6 percentage of participants |
| Placebo | Percentage of Participants With Abnormal Weight Gain and Weight Loss up to 10 Weeks | PCS Weight Loss | 0.8 percentage of participants |
| Duloxetine | Percentage of Participants With Abnormal Weight Gain and Weight Loss up to 10 Weeks | PCS Weight Gain | 1.2 percentage of participants |
| Duloxetine | Percentage of Participants With Abnormal Weight Gain and Weight Loss up to 10 Weeks | PCS Weight Loss | 3.1 percentage of participants |
p-value: 0.724Fisher Exact
p-value: 0.106Fisher Exact
Other Pre-specified
Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks
REU captures information regarding the participant's work status and/or health care utilization. Investigators gather information from medical records, psychiatric history, and direct questioning of the participant and his or her family to complete the questionnaire. Responses to each item, comparing baseline to endpoint, are characterized as Better, Same, or Worse. Better: an increase in time spent working/volunteering/holding a job, decrease in number of health care visits; Same: no change in time spent working/volunteering/holding a job, no change in number of health care visits; Worse: decrease in time spent working/volunteering/holding a job, increase in number of health care visits.
Time frame: Up to 10 weeks
Population: Intent-to-treat (ITT) participants with a baseline and at least 1 post-baseline REU value, last-observation-carried forward (LOCF) were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | ER Visits for Psychiatric Illness-Same | 100.0 percentage of participants |
| Placebo | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | Outpatient Visits to Other Physicians-Worse | 5.3 percentage of participants |
| Placebo | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | Outpatient Individual Visits-Same | 96.7 percentage of participants |
| Placebo | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | Average Hours Worked for Pay per Week-Better | 15.2 percentage of participants |
| Placebo | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | ER Visits for Psychiatric Illness-Worse | 0.0 percentage of participants |
| Placebo | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | Average Hours Worked for Pay per Week-Same | 64.3 percentage of participants |
| Placebo | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | Outpatient Group Visits-Same | 99.6 percentage of participants |
| Placebo | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | Average Hours Worked for Pay per Week-Worse | 20.5 percentage of participants |
| Placebo | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | ER Visits for Non-psychiatric Illness-Better | 5.7 percentage of participants |
| Placebo | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | How Long Participant Had This Job-Better | 25.2 percentage of participants |
| Placebo | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | Outpatient Individual Visits-Worse | 0.8 percentage of participants |
| Placebo | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | How Long Participant Had This Job-Same | 65.8 percentage of participants |
| Placebo | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | ER Visits for Non-psychiatric Illness-Same | 92.7 percentage of participants |
| Placebo | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | How Long Participant Had This Job-Worse | 9.0 percentage of participants |
| Placebo | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | Outpatient Individual Visits-Better | 2.4 percentage of participants |
| Placebo | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | Average Hours of Volunteer Work per Week-Better | 10.7 percentage of participants |
| Placebo | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | ER Visits for Non-psychiatric Illness-Worse | 1.6 percentage of participants |
| Placebo | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | Average Hours of Volunteer Work per Week-Same | 67.9 percentage of participants |
| Placebo | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | ER Visits for Psychiatric Illness-Better | 0.0 percentage of participants |
| Placebo | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | Average Hours of Volunteer Work per Week-Worse | 21.4 percentage of participants |
| Placebo | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | Outpatient Visits to Other Physicians-Better | 20.4 percentage of participants |
| Placebo | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | Psychiatric Visits-Better | 1.6 percentage of participants |
| Placebo | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | Outpatient Group Visits-Worse | 0.0 percentage of participants |
| Placebo | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | Psychiatric Visits-Same | 98.4 percentage of participants |
| Placebo | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | Outpatient Visits to Other Physicians-Same | 74.3 percentage of participants |
| Placebo | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | Psychiatric Visits-Worse | 0.0 percentage of participants |
| Placebo | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | Outpatient Group Visits-Better | 0.4 percentage of participants |
| Duloxetine | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | Psychiatric Visits-Worse | 0.0 percentage of participants |
| Duloxetine | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | Outpatient Group Visits-Better | 0.0 percentage of participants |
| Duloxetine | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | Outpatient Group Visits-Same | 100.0 percentage of participants |
| Duloxetine | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | Outpatient Group Visits-Worse | 0.0 percentage of participants |
| Duloxetine | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | Outpatient Individual Visits-Better | 0.8 percentage of participants |
| Duloxetine | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | Outpatient Individual Visits-Same | 99.2 percentage of participants |
| Duloxetine | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | Outpatient Individual Visits-Worse | 0.0 percentage of participants |
| Duloxetine | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | ER Visits for Psychiatric Illness-Better | 0.0 percentage of participants |
| Duloxetine | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | ER Visits for Psychiatric Illness-Same | 100.0 percentage of participants |
| Duloxetine | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | ER Visits for Psychiatric Illness-Worse | 0.0 percentage of participants |
| Duloxetine | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | ER Visits for Non-psychiatric Illness-Better | 3.7 percentage of participants |
| Duloxetine | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | ER Visits for Non-psychiatric Illness-Same | 95.5 percentage of participants |
| Duloxetine | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | ER Visits for Non-psychiatric Illness-Worse | 0.8 percentage of participants |
| Duloxetine | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | Outpatient Visits to Other Physicians-Better | 26.0 percentage of participants |
| Duloxetine | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | Outpatient Visits to Other Physicians-Same | 69.4 percentage of participants |
| Duloxetine | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | Outpatient Visits to Other Physicians-Worse | 4.5 percentage of participants |
| Duloxetine | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | Average Hours Worked for Pay per Week-Better | 18.9 percentage of participants |
| Duloxetine | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | Average Hours Worked for Pay per Week-Same | 69.4 percentage of participants |
| Duloxetine | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | Average Hours Worked for Pay per Week-Worse | 11.7 percentage of participants |
| Duloxetine | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | How Long Participant Had This Job-Better | 20.2 percentage of participants |
| Duloxetine | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | How Long Participant Had This Job-Same | 69.7 percentage of participants |
| Duloxetine | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | How Long Participant Had This Job-Worse | 10.1 percentage of participants |
| Duloxetine | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | Average Hours of Volunteer Work per Week-Better | 11.1 percentage of participants |
| Duloxetine | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | Average Hours of Volunteer Work per Week-Same | 72.2 percentage of participants |
| Duloxetine | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | Average Hours of Volunteer Work per Week-Worse | 16.7 percentage of participants |
| Duloxetine | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | Psychiatric Visits-Better | 0.8 percentage of participants |
| Duloxetine | Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks | Psychiatric Visits-Same | 99.2 percentage of participants |
p-value: 0.241Likelihood Ratio Chi-squared
p-value: 0.087Likelihood Ratio Chi-squared
p-value: 0.414Likelihood Ratio Chi-squared
p-value: 0.332Likelihood Ratio Chi-squared
p-value: 0.183Likelihood Ratio Chi-squared
p-value: 0.666Likelihood Ratio Chi-squared
p-value: 0.89Likelihood Ratio Chi-squared
p-value: 0.413Likelihood Ratio Chi-squared