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

Conditions

Osteoarthritis

Brief summary

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

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.

Related papers

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Interventions

DRUGcelecoxib

oral, 100 mg bid

DRUGOxycodone

oral, 20 mg bid

DRUGplacebo

oral bid

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

OTHER

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

40 Years to 70 Years

Healthy volunteers

No

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

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline in Knee Pain Intensity Measured by Numeric Rating Scale (NRS) at Week 12	Baseline, 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.
Change From Baseline in Knee Pain Intensity Measured by Visual Analog Scale (VAS) at Week 12	Baseline, 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.
Change From Baseline in Knee Adduction Moment at Week 12	Baseline, 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).
Change From Baseline in Western Ontario and McMaster (WOMAC) Osteoarthritis Index Pain Subscale Score at Week 12	Baseline, 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.
Change From Baseline in Western Ontario and McMaster (WOMAC) Osteoarthritis Index Physical Function Subscale Score at Week 12	Baseline, 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.
Change From Baseline in Western Ontario and McMaster (WOMAC) Osteoarthritis Index Stiffness Subscale Score at Week 12	Baseline, 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.
Change From Baseline in Western Ontario and McMaster (WOMAC) Osteoarthritis Index Total Score at Week 12	Baseline, 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.
Change From Baseline in Quadriceps Inhibition at Week 12	Baseline, Week 12	Quadriceps inhibition was assessed in terms of flexion-extension range of motion and normalized mid stance knee flexion angle in degrees.
Change From Baseline in Peak Ground Reaction Force at Week 12	Baseline, 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.
Change From Baseline in Total Ground Reaction Force at Week 12	Baseline, Week 12	Change from baseline in total ground reaction force in body weight\*seconds was assessed with the help of a multicomponent force plate.
Change From Baseline in Stride Length at Week 12	Baseline, Week 12	The level walking was assessed by stride length; assessment was done based on 6 stride cycles over a range of walking speeds.
Change From Baseline in Walking Speed at Week 12	Baseline, Week 12	Change from baseline in walking speed in meters per second was assessed.
Change From Baseline in Cadence at Week 12	Baseline, Week 12	Cadence was defined as the rate at which a person walk, expressed in steps per minute.
Change From Baseline in Patient Global Assessment of Arthritic Condition (PGAAC) Score at Week 12	Baseline, 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.

Countries

United States

Participant flow

Pre-assignment details

Total 6 participants were randomized to receive 1 of 6 possible treatment sequences of ABC, ACB. BAC, BCA, CAB, CBA (where: A=placebo, B=celecoxib, C=oxycodone) in treatment periods 1, 2 and 3 (each 2-week treatment period was separated by a 2-week washout period).

Participants by arm

Arm	Count
All Participants All randomized participants who received placebo matched to celecoxib and oxycodone, celecoxib 100 mg and oxycodone 20 mg orally, twice daily in one of the 6 treatment sequences in each of three treatment periods.	6
Total	6

Baseline characteristics

Characteristic	All Participants
Age, Continuous	62.5 Years STANDARD_DEVIATION 4.8
Sex: Female, Male Female	2 Participants
Sex: Female, Male Male	4 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	5 / 6	4 / 6	6 / 6
serious Total, serious adverse events	0 / 6	0 / 6	0 / 6

Outcome results

Primary