A Pilot Study Assessing the Treatment Responsiveness of a Novel Osteoarthritis Stiffness Scale

Study Overview
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Brief Summary
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Osteoarthritis is a common, chronic, progressive, skeletal, degenerative disorder that frequently affects several joints such as knee, hip, spine and hands.This placebo-controlled clinical trial assessed the effects of naproxen sodium, acetaminophen and celecoxib on stiffness in subjects with osteoarthritis.

Detailed Description
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The primary objective of the study was to assess the responsiveness of the Brief Arthritis Stiffness Scale (BASS) for detecting treatment effects of common over-the-counter (OTC) analgesics and a common prescription analgesic in subjects with knee osteoarthritis.

Official Title
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A Pilot Study Assessing the Treatment Responsiveness of a Novel Osteoarthritis Stiffness Scale

Conditions
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Osteoarthritis, Knee

Intervention / Treatment
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* Drug: Naproxen Sodium (Aleve, BAY117031)
* Drug: Acetaminophen ER
* Drug: Celecoxib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 40 and 80 years Body Mass Index (BMI) between 18 and <40 kg/m^2 Unilateral or bilateral osteoarthritis of the knee Diagnostic quality radiography of the target knee performed no more than 1 year prior to baseline showing evidence of osteoarthritis (OA) with Kellgren and Lawrence grade of II or III Joint Stiffness Severity score ≥3.0 on a 0-10 numerical rating scale (NRS) at screening Exclusion Criteria: History of underlying inflammatory arthropathy, rheumatoid arthritis or fibromyalgia History of or scheduled for target knee replacement surgery Recent injury in target knee (past 4 months)

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 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: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A-D-C-B<br>Participants received naproxen 660 mg daily for 3 days and 440 mg on the fourth day; followed by placebo for 4 days; followed by celecoxib 200 mg daily for 3 days and 100 mg on the fourth day; followed by acetaminophen 3900 mg daily for 3 days and 1300 mg on the fourth day. Treatment periods were separated by a washout period of 3 to 7 days. | Drug: Naproxen Sodium (Aleve, BAY117031)<br>* 660 mg daily for 3 days, 440 mg on the fourth day, over-encapsulated tablet, oral (Treatment A)<br>Drug: Acetaminophen ER<br>* 3900 mg daily for 3 days, 1300 mg on the fourth day, over-encapsulated extended release (ER) tablet, oral (Treatment B)<br>Drug: Celecoxib<br>* 200 mg daily for 3 days, 100 mg on the fourth day, over-encapsulated capsule, oral (Treatment C)<br>Drug: Placebo<br>* Over-encapsulation capsule, 4 days, oral (Treatment D)<br>|
| Experimental: Treatment B-C-D-A<br>Participants received acetaminophen 3900 mg daily for 3 days and 1300 mg on the fourth day; followed by celecoxib 200 mg daily for 3 days and 100 mg on the fourth day; followed by placebo for 4 days; followed by naproxen 660 mg daily for 3 days and 440 mg on the fourth day. Treatment periods were separated by a washout period of 3 to 7 days. | Drug: Naproxen Sodium (Aleve, BAY117031)<br>* 660 mg daily for 3 days, 440 mg on the fourth day, over-encapsulated tablet, oral (Treatment A)<br>Drug: Acetaminophen ER<br>* 3900 mg daily for 3 days, 1300 mg on the fourth day, over-encapsulated extended release (ER) tablet, oral (Treatment B)<br>Drug: Celecoxib<br>* 200 mg daily for 3 days, 100 mg on the fourth day, over-encapsulated capsule, oral (Treatment C)<br>Drug: Placebo<br>* Over-encapsulation capsule, 4 days, oral (Treatment D)<br>|
| Experimental: Treatment C-A-B-D<br>Participants received celecoxib 200 mg daily for 3 days and 100 mg on the fourth day; followed by naproxen 660 mg daily for 3 days and 440 mg on the fourth day; followed by acetaminophen 3900 mg daily for 3 days and 1300 mg on the fourth day; followed by placebo for 4 days. Treatment periods were separated by a washout period of 3 to 7 days. | Drug: Naproxen Sodium (Aleve, BAY117031)<br>* 660 mg daily for 3 days, 440 mg on the fourth day, over-encapsulated tablet, oral (Treatment A)<br>Drug: Acetaminophen ER<br>* 3900 mg daily for 3 days, 1300 mg on the fourth day, over-encapsulated extended release (ER) tablet, oral (Treatment B)<br>Drug: Celecoxib<br>* 200 mg daily for 3 days, 100 mg on the fourth day, over-encapsulated capsule, oral (Treatment C)<br>Drug: Placebo<br>* Over-encapsulation capsule, 4 days, oral (Treatment D)<br>|
| Experimental: Treatment D-B-A-C<br>Participants received placebo for 4 days; followed by acetaminophen 3900 mg daily for 3 days and 1300 mg on the fourth day; followed by naproxen 660 mg daily for 3 days and 440 mg on the fourth day; followed by celecoxib 200 mg daily for 3 days and 100 mg on the fourth day. Treatment periods were separated by a washout period of 3 to 7 days | Drug: Naproxen Sodium (Aleve, BAY117031)<br>* 660 mg daily for 3 days, 440 mg on the fourth day, over-encapsulated tablet, oral (Treatment A)<br>Drug: Acetaminophen ER<br>* 3900 mg daily for 3 days, 1300 mg on the fourth day, over-encapsulated extended release (ER) tablet, oral (Treatment B)<br>Drug: Celecoxib<br>* 200 mg daily for 3 days, 100 mg on the fourth day, over-encapsulated capsule, oral (Treatment C)<br>Drug: Placebo<br>* Over-encapsulation capsule, 4 days, oral (Treatment D)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sum of Change in Brief Arthritis Stiffness Scale (BASS) Scores Over the 4-day Treatment Period | Brief Arthritis Stiffness Scale (BASS) is a patient-reported outcome (PRO) instrument measuring of the severity of osteoarthritis-related stiffness in the target knee joint. The BASS score ranges from 0 to 40 and a higher score indicates worse stiffness. This endpoint was calculated by summing the changes from baseline (CFB) in BASS scores at Days 2, 3, and 4 of the treatment periods. | 4 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Brief Arthritis Stiffness Scale (BASS) Score at Each Time Point | Brief Arthritis Stiffness Scale (BASS) is a patient-reported outcome (PRO) instrument measuring of the severity of osteoarthritis-related stiffness in the target knee joint. The BASS score ranges from 0 to 40 and a higher score indicates worse stiffness. | 4 days | 
| Change From Baseline in Brief Arthritis Stiffness Scale (BASS) Score at Day 4 | Brief Arthritis Stiffness Scale (BASS) is a patient-reported outcome (PRO) instrument measuring of the severity of osteoarthritis-related stiffness in the target knee joint. The BASS score ranges from 0 to 40 and a higher score indicates worse stiffness. | Day 4 |