Duloxetine Versus Placebo for Osteoarthritis Knee Pain

Study Overview
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Brief Summary
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The primary purpose of this study is to determine if duloxetine reduces pain severity in patients with osteoarthritis knee pain.

Official Title
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Duloxetine 60 to 120 mg Versus Placebo in the Treatment of Patients With Osteoarthritis Knee Pain

Conditions
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Osteoarthritis Knee Pain

Intervention / Treatment
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* Drug: Duloxetine
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female outpatients with osteoarthritis knee pain. Exclusion Criteria: Cardiovascular, hepatic, renal, respiratory, or hematologic illness, or other medical or psychiatric condition that, in the opinion of the investigator, would compromise participation or be likely to lead to hospitalization during the course of the study. Acute liver injury (such as hepatitis) or severe cirrhosis. Previous exposure to duloxetine. Body Mass Index (BMI) over 40. Major depressive disorder. Daily use of narcotics.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>duloxetine 30 mg, daily (QD), by mouth (PO) for 1 week then duloxetine 60 mg QD, PO for 6 weeks then duloxetine 60 mg or 120 mg QD, PO for 6 weeks | Drug: Duloxetine<br> <br> * Other names: Cymbalta;|
| Placebo Comparator: B<br>placebo daily (QD), by mouth (PO) for 13 weeks | Drug: placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weekly Change From Baseline in the 24-Hour Average Pain Rating Using an 11-Point Numerical Likert Scale Patient Diary | This is an ordinal scale assessing the 24-hour average pain with scores from 0 (no pain) to 10 (worst possible pain). | Over 13 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Global Impression of Improvement at 13 Week Endpoint | A scale that measures the patient's perception of improvement at the time of assessment. The score ranges from 1 (very much better) to 7 (very much worse). | 13 Weeks | 
| Change From Baseline to 13 Week Endpoint in Western Ontario and McMaster Osteoarthritis Index (WOMAC) - Pain Subscale | The WOMAC index (pain, stiffness, physical function subscales) will be completed by the patient. The pain subscale has 5 questions on pain associated with every day tasks. Each question is answered using a 5-point Likert scale (0 to 4). The pain subscale has a range of scores of 0 (none) to 20 (extreme). | Baseline and 13 Weeks | 
| Change From Baseline to 13 Week Endpoint in Western Ontario and McMaster Osteoarthritis Index (WOMAC) - Stiffness Subscale | The WOMAC index (pain, stiffness, physical function subscales) will be completed by the patient. The stiffness subscale has 2 questions on stiffness associated with time of day (morning versus later in the day). Each question is answered using a 5-point Likert scale (0 to 4). The pain subscale has a range of scores of 0 (none) to 8 (extreme). | Baseline and 13 Weeks | 
| Change From Baseline to 13 Week Endpoint in Western Ontario and McMaster Osteoarthritis Index (WOMAC) - Physical Function Subscale | The WOMAC index (pain, stiffness, physical function subscales) will be completed by the patient. The physical function subscale has 17 questions on physical function difficulties with every day tasks. Each question is answered using a 5-point Likert scale (0 to 4). The physical function subscale has a range of scores of 0 (none) to 68 (extreme). | Baseline and 13 Weeks | 
| Change From Baseline to 13 Week Endpoint in Western Ontario and McMaster Osteoarthritis Index (WOMAC) - Total Score | The WOMAC index (pain, stiffness, physical function subscales) will be completed by the patient. The index has 24 questions. Each question is answered using a 5-point Likert scale (0 to 4). The Total score has a range from 0 (none) to 96 (extreme). | Baseline and 13 Weeks | 
| Change From Baseline to 13 Week Endpoint in Weekly Mean of the 24-Hour Worst Pain Score | This is an ordinal scale with scores from 0 (no pain) to 10 (worst possible pain). The value is the change from baseline in the weekly mean of the 24-hour worst pain score on the scale. | Baseline and 13 Weeks | 
| Weekly Change From Baseline in the 24-Hour Worst Pain Score | This is an ordinal scale with scores from 0 (no pain) to 10 (worst possible pain). The value is the change from baseline in the weekly mean of the 24-hour worst pain score on the scale. | Over 13 Weeks | 
| Change From Baseline to 13 Week Endpoint in Weekly Mean of 24-Hour Average Pain in the Re-Randomized Treatment Phase | This is an ordinal scale with scores from 0 (no pain) to 10 (worst possible pain). This value is the change from baseline in the weekly mean of the 24-hour average pain score on the scale. | Baseline and 13 Weeks | 
| Change From Baseline to 13 Week Endpoint in Clinical Global Impression of Severity | Measures severity of illness at the time of assessment compared with start of treatment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients. | Baseline and 13 Weeks | 
| Change From Baseline to 13 Week Endpoint in Brief Pain Inventory (BPI) - Worst Pain Score | A self-reported scale that measures the severity of pain based on the worst pain experienced over the past 24-hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). | Baseline and 13 Weeks | 
| Change From Baseline to 13 Week Endpoint in Brief Pain Inventory - Least Pain Score | A self-reported scale that measures the severity of pain based on the least pain experienced over the past 24-hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). | Baseline and 13 Weeks | 
| Change From Baseline to 13 Week Endpoint in Brief Pain Inventory - Average Pain Score | A self-reported scale that measures the severity of pain based on the average pain experienced over the past 24-hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). | Baseline and 13 Weeks | 
| Change From Baseline to 13 Week Endpoint in Brief Pain Inventory - Pain Right Now Score | A self-reported scale that measures the severity of pain based on the pain right now. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). | Baseline and 13 Weeks | 
| Change From Baseline to 13 Week Endpoint in Brief Pain Inventory Interference Score - General Activity | A self-reported scale that measures the interference of pain in the past 24 hours on general acitivity. The Interference scores range from 0 (does not interfere) to 10 (completely interferes). | Baseline and 13 Weeks | 
| Change From Baseline to 13 Week Endpoint in Brief Pain Inventory Interference Score - Mood | A self-reported scale that measures the interference of pain in the past 24 hours on mood. The Interference scores range from 0 (does not interfere) to 10 (completely interferes). | Baseline and 13 Weeks | 
| Change From Baseline to 13 Week Endpoint in Brief Pain Inventory Interference Score - Walking Ability | A self-reported scale that measures the interference of pain in the past 24 hours on walking ability. The Interference scores range from 0 (does not interfere) to 10 (completely interferes). | Baseline and 13 Weeks | 
| Change From Baseline to 13 Week Endpoint in Brief Pain Inventory Interference Score - Normal Work | A self-reported scale that measures the interference of pain in the past 24 hours on normal work. The Interference scores range from 0 (does not interfere) to 10 (completely interferes). | Baseline and 13 Weeks | 
| Change From Baseline to 13 Week Endpoint in Brief Pain Inventory Interference Score - Relations With Other People | A self-reported scale that measures the interference of pain in the past 24 hours on relations with other people. The Interference scores range from 0 (does not interfere) to 10 (completely interferes). | Baseline and 13 Weeks | 
| Change From Baseline to 13 Week Endpoint in Brief Pain Inventory Interference Score - Sleep | A self-reported scale that measures the interference of pain in the past 24 hours on sleep. The Interference scores range from 0 (does not interfere) to 10 (completely interferes). | Baseline and 13 Weeks | 
| Change From Baseline to 13 Week Endpoint in Brief Pain Inventory Interference Score - Enjoyment of Life | A self-reported scale that measures the interference of pain in the past 24 hours on enjoyment of life. The Interference scores range from 0 (does not interfere) to 10 (completely interferes). | Baseline and 13 Weeks | 
| Change From Baseline to 13 Week Endpoint in Brief Pain Inventory Average Interference | A self-reported scale that measures interference of pain on average of the 7 questions assessing the interference of pain for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. The average Interference scores range from 0 (does not interfere) to 10 (completely interferes). | Baseline and 13 Weeks | 
| Response to Treatment - The Number of Participants With a >= 30% Reduction of Weekly Mean in 24-Hour Average Pain Severity Ratings | Number of participants who experienced a response to treatment, which was defined as having a >=30% reduction of the weekly mean in 24-hour average pain severity ratings. This is an ordinal scale with scores from 0 (no pain) to 10 (worst possible pain). | Over 13 Weeks | 
| Response to Treatment - The Number of Participants With a >=30% Reduction of Weekly Mean in 24-Hour Average Pain Severity Ratings in the Re-Randomized Treatment Phase | Number of participants who experienced a response to treatment, which was defined as having a >=30% reduction of the weekly mean in 24-hour average pain severity ratings. Response to treatment over the last 6 weeks of the trial (after patients were re-randomized) were compared to baseline measures. | Over 13 Weeks | 
| Change From Baseline to 13 Week Endpoint in Medical Outcomes Study Short Form-36 (SF-36) - Mental Health Component Summary | A self-reported questionnaire that consists of 36 questions covering 8 health domains. 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. The mental component summary (MCS) has been constructed based on the 8 SF-36 domains. | Baseline and 13 Weeks | 
| Change From Baseline to 13 Week Endpoint in Medical Outcomes Study Short Form-36 (SF-36) - Physical Component Summary | A self-reported questionnaire that consists of 36 questions covering 8 health domains. 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. The physical component summary (PCS) has been constructed based on the 8 SF-36 domains. | Baseline and 13 Weeks | 
| Change From Baseline to 13 Week Endpoint in Euro-Quality of Life - 5 Dimensions (EQ-5D): US Based Index Score | The EQ-5D is an assessment of one's overall health. Consists of 5 items. Patients choose 1 of 3 options that best describe the status of each item. The EQ-5D US based index scores range from -0.11 to 1.0 where a score of 1.0 indicates perfect health. A positive change from baseline indicates health improvement. | Baseline and 13 Weeks | 
| Change From Baseline to 13 Week Endpoint in Beck Depression Inventory-II - Total Score | A 21-item, patient-completed questionnaire to assess characteristics of depression. Each of the 21 items corresponding to a symptom of depression is summed to give a single score. There is a four-point scale for each item ranging from 0 to 3. Total score of 0-13 is considered minimal range, 14-19 is mild, 20-28 is moderate, and 29-63 is severe. | Baseline and 13 Weeks | 
| Change From Baseline to 13 Week Endpoint in Hospital Anxiety and Depression Scale (HADS) - Anxiety Subscale | A 14-item questionnaire with 2 subscales: anxiety and depression. Each item is rated on a 4-point scale, giving maximum scores of 21 for anxiety and depression. Scores of 11 or more on either subscale are considered to be a significant 'case' of psychological morbidity, while scores of 8-10 represent 'borderline' and 0-7, 'normal.' | Baseline and 13 Weeks | 
| Statistically Significant Change From Baseline to 13 Week Endpoint in Laboratory Data - Chemistry Analytes: Alkaline Phosphatase | Change from baseline to endpoint in alkaline phosphatase using central laboratory reference ranges. | Baseline and 13 Weeks | 
| Statistically Significant Change From Baseline to 13 Week Endpoint in Laboratory Data - Chemistry Analytes: Uric Acid | Change from baseline to endpoint in uric acid using central laboratory reference ranges. | Baseline and 13 Weeks | 
| Change From Baseline to 13 Week Endpoint in Vital Signs - Pulse Rate | Pulse rate (heart rate) measured in the sitting position. | Baseline and 13 Weeks | 
| Change From Baseline to 13 Week Endpoint in Vital Signs - Blood Pressure (BP) Diastolic | Diastolic blood pressure measured in the sitting position. | Baseline and 13 Weeks | 
| Change From Baseline to 13 Week Endpoint in Vital Signs - Blood Pressure (BP) Systolic | Systolic blood pressure measured in the sitting position. | Baseline and 13 Weeks | 
| Change From Baseline to 13 Week Endpoint in Vital Signs - Weight |  | Baseline and 13 Weeks |