Duloxetine vs. Placebo in the Treatment of 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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Protocol F1J-MC-HMFG 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: Serious 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. Previous exposure to duloxetine.

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> | Drug: Duloxetine<br>* duloxetine 30 mg every day (QD), by mouth (PO) for 1 week, then duloxetine 60 mg QD, PO for 6 weeks, followed by duloxetine 60 mg QD, PO for 6 weeks for responders or duloxetine 120 mg QD, PO for 6 weeks for non-responders<br>* Other names: Cymbalta;|
| Placebo Comparator: B<br> | Drug: Placebo<br>* placebo every day (QD), by mouth (PO) for 13 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Brief Pain Inventory (BPI) 24-hour Average Rating | A self-reported scale that measures the severity of pain based on the average pain over the past 24-hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). Changes are timepoint minus baseline. | Baseline, Week 4, Week 7, Week 13 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Values at 13 Week Endpoint in Patient Global Impression of Improvement (PGI-I) | A scale that measures the patient'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). | 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 Universities 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 Universities 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 Weekly Mean of the 24-Hour Average Pain and Worst Pain Scores | This assesses the weekly mean of the average pain and worst pain experienced over the last 24-hours. This is an ordinal scale with scores for each subscale (average pain and worst pain) ranging from 0 (no pain) to 10 (worst possible pain). Change = endpoint minus baseline. | Baseline and 13 Weeks | 
| Change From Baseline to 13 Week Endpoint in Clinical Global Impression of Severity (CGI-S) | Measures severity of illness at the time of assessment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients. | Baseline and 13 Weeks | 
| Number of Participants Who Responded to Treatment at 13 Week Endpoint | Response to treatment was defined as a ≥ 30% reduction from baseline to endpoint in Brief Pain Inventory (BPI) average pain score. The BPI 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). | 13 Weeks | 
| Mean Change From Baseline to 13 Week Endpoint in Medical Outcomes Study Short Form-36 (SF-36) Medical Component Summary (MCS), Physical Component Summary (PCS), and Domain Scores | MCS and PCS scores=0-100 (higher scores indicate better health status). Domain scores:general health=5-25, physical functioning=10-30, Role-physical=4-8, Role-emotional=3-6, social functioning=2-10, bodily pain=2-11, vitality=4-24, mental health=5-30. | Baseline and 13 Weeks | 
| Change From Baseline to 13 Week Endpoint in EuroQoL Questionnaire - 5 Dimension (EQ-5D) | 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 (BDI-II) | 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 - Anxiety Subscale (HADS-A) | A 14-item questionnaire with 2 subscales: anxiety (7 items) and depression (7 items). Each item is rated on a 4-point scale (0 to 3), giving maximum scores of 21 for anxiety subscale. Scores of 11 or more 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 | 
| Change From Baseline to 13 Week Endpoint in Brief Pain Inventory (BPI) Severity: 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 Severity: 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 Severity: 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 Severity: 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: General Activity | A self-reported scale that measures the interference of pain in the past 24 hours for 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: 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: 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: 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: 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: 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: 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 Interference: 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 | 
| Adverse Events Reported as Reason for Discontinuation |  | over 13 weeks | 
| Statisically Significant Change From Baseline to 13 Week Endpoint in Laboratory Analytes |  | Baseline and 13 Weeks | 
| Statisically Significant Change From Baseline to 13 Week Endpoint in Chloride |  | Baseline and 13 Week Endpoint | 
| Change From Baseline to 13 Week Endpoint in Vital Signs - Heart Rate |  | Baseline and 13 Weeks | 
| Change From Baseline to 13 Week Endpoint in Vital Signs - Blood Pressure |  | Baseline and 13 Weeks | 
| Change From Baseline to 13 Week Endpoint in Vital Signs - Weight |  | Baseline and 13 Weeks | 
| Change From Baseline to 13 Week Endpoint in Brief Pain Inventory - Average Pain Score in Nonresponders | A self-reported scale that measures the severity of pain based on the average pain over the past 24-hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). Non-Responders were defined as patients with a <30% reduction from baseline to visit 4 (7 weeks) in Brief Pain Inventory (BPI) average pain score. | Baseline and 13 Weeks | 
| Number of Nonresponders at Week 7 Who Responded at Week 13 Endpoint | Response was defined as a >=30% reduction from baseline to endpoint in Brief Pain Inventory average pain score. Nonresponders were defined as participants with a <30% reduction from baseline to Visit 4 (7 Weeks) in Brief Pain Inventory average pain score. | 13 Weeks | 
| Adverse Events Reported as Reason for Discontinuation in Nonresponders | Nonresponders were defined as participants with a <30% reduction from baseline to Visit 7 (7 weeks) in Brief Pain Inventory average pain score. | over 13 Weeks |