Osteoarthritis, Knee
Conditions
Brief summary
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
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.
Interventions
660 mg daily for 3 days, 440 mg on the fourth day, over-encapsulated tablet, oral (Treatment A)
DRUGAcetaminophen ER
3900 mg daily for 3 days, 1300 mg on the fourth day, over-encapsulated extended release (ER) tablet, oral (Treatment B)
DRUGCelecoxib
200 mg daily for 3 days, 100 mg on the fourth day, over-encapsulated capsule, oral (Treatment C)
DRUGPlacebo
Over-encapsulation capsule, 4 days, oral (Treatment D)
Sponsors
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sum of Change in Brief Arthritis Stiffness Scale (BASS) Scores Over the 4-day Treatment Period | 4 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Brief Arthritis Stiffness Scale (BASS) Score at Each Time Point | 4 days | 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. |
| Change From Baseline in Brief Arthritis Stiffness Scale (BASS) Score at Day 4 | 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. |
Countries
United States
Participant flow
Recruitment details
Study was conducted at multiple centers in the US between 29 June 2018 (first participant first visit) and 14 June 2019 (last participant last visit).
Pre-assignment details
Overall, 209 participants were screened. Of them, 168 participants were screen failures, and 41 subjects were randomized to study treatments.
Participants by arm
| Arm | Count |
|---|---|
| Treatment A-D-C-B 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. | 10 |
| Treatment B-C-D-A 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. | 10 |
| Treatment C-A-B-D 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. | 11 |
| Treatment D-B-A-C 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. | 10 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 1 |
| Overall Study | Non-compliance with study drug | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Treatment A-D-C-B | Total | Treatment D-B-A-C | Treatment C-A-B-D | Treatment B-C-D-A |
|---|---|---|---|---|---|
| Age, Continuous | 62.4 Years STANDARD_DEVIATION 9.2 | 61.2 Years STANDARD_DEVIATION 8.19 | 59.6 Years STANDARD_DEVIATION 8.28 | 61.6 Years STANDARD_DEVIATION 7.55 | 61.3 Years STANDARD_DEVIATION 8.77 |
| Brief Arthritis Stiffness Scale (BASS) Treatment period 1 | 26.7 Scores on a scale STANDARD_DEVIATION 4.9 | 26.0 Scores on a scale STANDARD_DEVIATION 5.31 | 23.1 Scores on a scale STANDARD_DEVIATION 5.35 | 27.8 Scores on a scale STANDARD_DEVIATION 5.56 | 25.8 Scores on a scale STANDARD_DEVIATION 5.05 |
| Brief Arthritis Stiffness Scale (BASS) Treatment period 2 | 25.8 Scores on a scale STANDARD_DEVIATION 7.74 | 23.8 Scores on a scale STANDARD_DEVIATION 7.74 | 25.3 Scores on a scale STANDARD_DEVIATION 4.64 | 22.3 Scores on a scale STANDARD_DEVIATION 9.74 | 21.8 Scores on a scale STANDARD_DEVIATION 8.32 |
| Brief Arthritis Stiffness Scale (BASS) Treatment period 3 | 26.3 Scores on a scale STANDARD_DEVIATION 5.56 | 22.7 Scores on a scale STANDARD_DEVIATION 8.69 | 24.0 Scores on a scale STANDARD_DEVIATION 6.48 | 22.9 Scores on a scale STANDARD_DEVIATION 10.29 | 17.7 Scores on a scale STANDARD_DEVIATION 10.03 |
| Brief Arthritis Stiffness Scale (BASS) Treatment period 4 | 21.9 Scores on a scale STANDARD_DEVIATION 10.56 | 22.5 Scores on a scale STANDARD_DEVIATION 8.68 | 23.8 Scores on a scale STANDARD_DEVIATION 7.92 | 24.2 Scores on a scale STANDARD_DEVIATION 9.95 | 20.3 Scores on a scale STANDARD_DEVIATION 6.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 4 Participants | 1 Participants | 2 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 37 Participants | 9 Participants | 9 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 16 Participants | 5 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 24 Participants | 5 Participants | 8 Participants | 5 Participants |
| Sex: Female, Male Female | 9 Participants | 33 Participants | 7 Participants | 11 Participants | 6 Participants |
| Sex: Female, Male Male | 1 Participants | 8 Participants | 3 Participants | 0 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 39 | 0 / 40 | 0 / 40 | 0 / 39 |
| other Total, other adverse events | 5 / 39 | 8 / 40 | 10 / 40 | 3 / 39 |
| serious Total, serious adverse events | 0 / 39 | 0 / 40 | 0 / 40 | 0 / 39 |
Outcome results
Primary
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.
Time frame: 4 days
Population: Per-protocol (PP) population: all subjects who were randomly assigned and had taken at least one dose of IMP without major protocol violations that could affect the evaluability of the primary efficacy parameter.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Naproxen | Sum of Change in Brief Arthritis Stiffness Scale (BASS) Scores Over the 4-day Treatment Period | -12.6 Scores on a scale | Standard Error 5.46 |
| Acetaminophen ER | Sum of Change in Brief Arthritis Stiffness Scale (BASS) Scores Over the 4-day Treatment Period | -13.6 Scores on a scale | Standard Error 5.46 |
| Celecoxib | Sum of Change in Brief Arthritis Stiffness Scale (BASS) Scores Over the 4-day Treatment Period | -11.7 Scores on a scale | Standard Error 5.46 |
| Placebo | Sum of Change in Brief Arthritis Stiffness Scale (BASS) Scores Over the 4-day Treatment Period | -2.3 Scores on a scale | Standard Error 5.47 |
Secondary
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.
Time frame: 4 days
Population: Per-protocol (PP) population: all subjects who were randomly assigned and had taken at least one dose of IMP without major protocol violations that could affect the evaluability of the primary efficacy parameter.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Naproxen | Absolute Brief Arthritis Stiffness Scale (BASS) Score at Each Time Point | Day 1 | 23.0 Scores on a scale | Standard Error 1.84 |
| Naproxen | Absolute Brief Arthritis Stiffness Scale (BASS) Score at Each Time Point | Day 2 | 20.8 Scores on a scale | Standard Error 1.62 |
| Naproxen | Absolute Brief Arthritis Stiffness Scale (BASS) Score at Each Time Point | Day 3 | 18.4 Scores on a scale | Standard Error 1.97 |
| Naproxen | Absolute Brief Arthritis Stiffness Scale (BASS) Score at Each Time Point | Day 4 | 18.1 Scores on a scale | Standard Error 1.97 |
| Acetaminophen ER | Absolute Brief Arthritis Stiffness Scale (BASS) Score at Each Time Point | Day 2 | 19.7 Scores on a scale | Standard Error 1.62 |
| Acetaminophen ER | Absolute Brief Arthritis Stiffness Scale (BASS) Score at Each Time Point | Day 3 | 18.4 Scores on a scale | Standard Error 1.97 |
| Acetaminophen ER | Absolute Brief Arthritis Stiffness Scale (BASS) Score at Each Time Point | Day 4 | 18.0 Scores on a scale | Standard Error 1.97 |
| Acetaminophen ER | Absolute Brief Arthritis Stiffness Scale (BASS) Score at Each Time Point | Day 1 | 23.3 Scores on a scale | Standard Error 1.84 |
| Celecoxib | Absolute Brief Arthritis Stiffness Scale (BASS) Score at Each Time Point | Day 3 | 18.9 Scores on a scale | Standard Error 1.98 |
| Celecoxib | Absolute Brief Arthritis Stiffness Scale (BASS) Score at Each Time Point | Day 2 | 20.6 Scores on a scale | Standard Error 1.62 |
| Celecoxib | Absolute Brief Arthritis Stiffness Scale (BASS) Score at Each Time Point | Day 4 | 18.5 Scores on a scale | Standard Error 1.97 |
| Celecoxib | Absolute Brief Arthritis Stiffness Scale (BASS) Score at Each Time Point | Day 1 | 24.6 Scores on a scale | Standard Error 1.84 |
| Placebo | Absolute Brief Arthritis Stiffness Scale (BASS) Score at Each Time Point | Day 4 | 22.0 Scores on a scale | Standard Error 1.97 |
| Placebo | Absolute Brief Arthritis Stiffness Scale (BASS) Score at Each Time Point | Day 2 | 23.2 Scores on a scale | Standard Error 1.62 |
| Placebo | Absolute Brief Arthritis Stiffness Scale (BASS) Score at Each Time Point | Day 1 | 22.6 Scores on a scale | Standard Error 1.85 |
| Placebo | Absolute Brief Arthritis Stiffness Scale (BASS) Score at Each Time Point | Day 3 | 22.4 Scores on a scale | Standard Error 1.98 |
Secondary
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.
Time frame: Day 4
Population: Per-protocol (PP) population: All subjects who were randomly assigned and had taken at least one dose of IMP without major protocol violations that could affect the evaluability of the primary efficacy parameter.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Naproxen | Change From Baseline in Brief Arthritis Stiffness Scale (BASS) Score at Day 4 | -5.2 Scores on a scale | Standard Error 1.97 |
| Acetaminophen ER | Change From Baseline in Brief Arthritis Stiffness Scale (BASS) Score at Day 4 | -5.3 Scores on a scale | Standard Error 1.97 |
| Celecoxib | Change From Baseline in Brief Arthritis Stiffness Scale (BASS) Score at Day 4 | -4.8 Scores on a scale | Standard Error 1.97 |
| Placebo | Change From Baseline in Brief Arthritis Stiffness Scale (BASS) Score at Day 4 | -1.3 Scores on a scale | Standard Error 1.97 |