Measuring Gait And Self-Reported Pain In Patients With Osteoarthritis Of The Knee Using Placebo/Oxycodone/Celecoxib.

Study Overview
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Brief Summary
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The Purpose of this trial is to evaluate the use of a cross-over trial design in an osteoarthritis population. We will determine the inter- and intra-subject variability in osteoarthritis (OA) endpoints and evaluate if efficacy can be detected by measuring OA endpoints following treatment with 2 different types of analgesics in a crossover study of this design.

Detailed Description
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Methodology study to evaluate the use of a cross over design and gait analysis. The study was terminated by mutual consent with the study site at a meeting on the 1 April 2009, because of slow recruitment due to a high screen fail rate. The study was not stopped for safety reasons.

Official Title
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MEASURES OF GAIT AND SELF-REPORTED PAIN IN PATIENTS WITH OSTEOARTHRITIS OF THE KNEE: A RANDOMIZED, SINGLE-BLIND WASHOUT, DOUBLE-BLIND TREATMENT, DOUBLE DUMMY CROSS-OVER PILOT TRIAL USING PLACEBO, OXYCODONE AND CELECOXIB (A9011030)

Conditions
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Osteoarthritis

Intervention / Treatment
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* Drug: celecoxib
* Drug: Oxycodone
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has been taking an NSAID at least 15 of the past 30 days for index knee pain Grades 2 or 3 OA as defined by the Kellgren and Lawrence Grading System of the medial tibiofemoral joint (joint space narrowing in the medial compartment > lateral compartment as assessed by x-ray) using the Altman Atlas of OA7. This must be documented with a report from an x-ray of the study joint taken either at screening or within 1 year prior to screening Subject meets American College of Rheumatology (ACR) clinical classification criteria for osteoarthritis of the knee, defined by the following: Knee pain and at least 3 of the following: oAge >50 oMorning stiffness <30 minutes oCrepitus on active motion oBony tenderness oBony enlargement oNo palpable warmth of synovium. Exclusion Criteria: Subject has a documented history of an allergic reaction (hives, rash, etc.) or a clinically significant intolerance to celecoxib, sulfonamides, aspirin, or opioids including oxycodone Significant pain outside the index knee, including significant hip or back pain that can not be distinguished from OA pain or that interferes with ability to walk. (Patients with bilateral knee OA will be allowed into the study. The index knee should be defined as the more painful knee Predominantly patellofemoral knee osteoarthritis in the index knee as assessed by clinical examination Subject who are unable to discontinue all formulations of prior analgesics other than acetaminophen during the Washout Period of the study, or who are anticipated to be unable to discontinue rescue medication for 24 hours prior to the respective visits. (Low dose aspirin may be taken for cardiac prophylaxis Excessive signal knee joint laxity indicative of functional ligamentous deficiency

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 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: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A<br> | Drug: celecoxib<br>* oral, 100 mg bid<br>|
| Active Comparator: B<br> | Drug: Oxycodone<br>* oral, 20 mg bid<br>|
| Placebo Comparator: C<br> | Drug: placebo<br>* oral bid<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Western Ontario and McMaster (WOMAC) Osteoarthritis Index Stiffness Subscale Score at Week 12 | WOMAC: Self-administered, disease-specific questionnaire, which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis (OA of the hip and/or knee). Stiffness was defined as a sensation of decreased ease of movement in study joint. The WOMAC stiffness subscale is a 2-item questionnaire used to assess the amount of stiffness experienced due to OA in the in the study joint during the past 48 hours. The WOMAC stiffness subscale score for each question ranges from 0 (minimum) to 4 (maximum), higher scores signifies worse stiffness. The stiffness subscale score ranges from 0 to 8, where higher scores indicated worse stiffness. | Baseline, Week 12 | 
| Change From Baseline in Western Ontario and McMaster (WOMAC) Osteoarthritis Index Total Score at Week 12 | WOMAC: Self-administered, disease-specific questionnaire, which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis (OA of the hip and/or knee). The WOMAC composite index was the sum of 24 individual questions regarding subscales of pain, stiffness and physical function (for each item score range: 0 [minimum] to 4 [maximum], higher score indicating worse study joint condition). Total score was sum of the 3 subscale scores, giving a possible overall score range of 0 (minimum) to 96 (maximum). Higher score indicating the worse level of pain, stiffness and physical function. | Baseline, Week 12 | 
| Change From Baseline in Knee Adduction Moment at Week 12 | Adduction (external) moment was defined as the ground-generated torque that forces the distal tibia toward the midline of the body, which forces the knee away from the midline, into a varus or bow-legged position. External knee adduction moment was assessed as percent body weight*height (%BW*ht). | Baseline, Week 12 | 
| Change From Baseline in Quadriceps Inhibition at Week 12 | Quadriceps inhibition was assessed in terms of flexion-extension range of motion and normalized mid stance knee flexion angle in degrees. | Baseline, Week 12 | 
| Change From Baseline in Peak Ground Reaction Force at Week 12 | Change from baseline in peak ground reaction force in body weight*seconds (BW*sec) was assessed with the help of a multicomponent force plate. | Baseline, Week 12 | 
| Change From Baseline in Total Ground Reaction Force at Week 12 | Change from baseline in total ground reaction force in body weight*seconds was assessed with the help of a multicomponent force plate. | Baseline, Week 12 | 
| Change From Baseline in Stride Length at Week 12 | The level walking was assessed by stride length; assessment was done based on 6 stride cycles over a range of walking speeds. | Baseline, Week 12 | 
| Change From Baseline in Walking Speed at Week 12 | Change from baseline in walking speed in meters per second was assessed. | Baseline, Week 12 | 
| Change From Baseline in Cadence at Week 12 | Cadence was defined as the rate at which a person walk, expressed in steps per minute. | Baseline, Week 12 | 
| Change From Baseline in Patient Global Assessment of Arthritic Condition (PGAAC) Score at Week 12 | The PGAAC is self-administered measure in which participants answered the following question: considering all the ways the OA in your signal knee affects you, how are you doing today?. Participants rated their condition using the following scale: 1= very good (no symptoms and no limitation of normal activities); 2= good (mild symptoms and no limitation of normal activities); 3= fair (moderate symptoms and limitation of some normal activities); 4= poor (severe symptoms and inability to carry out most normal activities); 5= very poor (very severe symptoms which are intolerable and inability to carry out all normal activities). Higher score indicated severe condition. | Baseline, Week 12 | 
| Change From Baseline in Western Ontario and McMaster (WOMAC) Osteoarthritis Index Physical Function Subscale Score at Week 12 | WOMAC: Self-administered, disease-specific questionnaire, which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis (OA of the hip and/or knee). Physical function refers to participant's ability to move around and perform usual activities of daily living. The WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to OA in in the study joint during past 48 hours. The WOMAC physical function subscale score for each question ranges from 0 (minimum) to 4 (maximum), higher scores signifies worse physical function. Physical function subscale scores range from 0 to 68, where higher scores indicated more difficulty in performing daily activities. | Baseline, Week 12 | 
| Change From Baseline in Knee Pain Intensity Measured by Numeric Rating Scale (NRS) at Week 12 | The severity of arthritis pain in participant's signal knee at the time of the visit was assessed using an 11-point NRS, ranging from 0 (no pain) to 10 (worst possible pain), where higher scores indicate worse pain. | Baseline, Week 12 | 
| Change From Baseline in Knee Pain Intensity Measured by Visual Analog Scale (VAS) at Week 12 | The severity of arthritis pain in participant's signal knee was assessed using a 100-millimeter (mm) VAS ranging from 0 mm = no pain and 100 mm = most severe pain. Higher score indicate more pain. | Baseline, Week 12 | 
| Change From Baseline in Western Ontario and McMaster (WOMAC) Osteoarthritis Index Pain Subscale Score at Week 12 | WOMAC: Self-administered, disease-specific questionnaire, which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis (OA of the hip and/or knee). The index consists of 24 questions (5 pain, 2 stiffness, and 17 physical function). The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to OA of to be replaced/replaced index joint (knee or hip) during past 48 hours. The WOMAC pain subscale score for each question ranges from 0 (minimum) to 4 (maximum), higher scores signifies worse pain. Pain subscale total score ranges from 0 to 20, with higher scores indicating worse pain. | Baseline, Week 12 |