Osteoarthritis, Hip, Osteoarthritis, Knee
Conditions
Keywords
Chronic treatment osteoarthritis, Celecoxib, Continuous Use, Intermittent Use
Brief summary
To determine whether continuous use of celecoxib over a 6-month period is more efficacious than usual or intermittent use in preventing spontaneous osteoarthritis flares of the knee and hip.
Interventions
DRUGCelecoxib
24 weeks of study treatment: 2 weeks open-label celecoxib 200 mg daily followed by 22 weeks of randomized double blind celecoxib 200 mg daily. Placebo used as flare medication when directed.
Sponsors
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Subject has been diagnosed, according to American College of Rheumatology guidelines, with osteoarthritis of the hip or knee and requires non-steroidal anti-inflammatory drugs (NSAIDs) to control their osteoarthritis pain and have access to a touch-tone telephone.
Exclusion criteria
* Subject has had surgery on index joint. * Subject has history of rheumatoid arthritis or fibromyalgia syndrome. * Subject has active gastrointestinal or cardiovascular disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Flare Events Per Time of Exposure to Study Medication | Period III (22 weeks) | Number of flare events per month during Period III (calculated as number of flares divided by number of months participant was enrolled during Period III). Flare was determined using pre-defined criteria, using an interactive voice response system. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient's Global Assessment of Arthritis | Period III | Participant's response to question Considering all the ways the osteoarthritis in your hip or knee affects you, how are you doing today? on scale from 1 (very good) to 5 (very poor). Scores analyzed as area under the curve (AUC) of participant's scores from each assessment in Period III. |
| Proportion of Days on Rescue Medication | Period III (22 weeks) | Days on rescue medication divided by number of days on study medication in Period III |
| Days on Flare Medication | Period III (22 weeks) | Number of days on flare medication per month per subject calculated as number of days on flare medication divided by the number of days on study medication in Period III |
| Change in Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Scores | Period III (22 weeks) | Score at end of Period III minus score at start of Period III. WOMAC assesses subject responses to 24 components regarding subscales of pain, stiffness and physical function (score range: 0=none to 4= extreme). Total score is sum of the 3 subscale scores. Negative change indicates improvement. |
| Area Under the Curve (AUCs) of Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Scores | Period III (22 weeks) | WOMAC assesses subject responses to 24 components regarding subscales of pain, stiffness and physical function (score range: 0=none to 4= extreme). Total score is sum of the 3 subscale scores. Scores analyzed as area under the curve (AUC) of participant's WOMAC scores from each assessment in Period III. |
| Time to Occurrence of First Osteoarthritis (OA) Flare | Period III (22 weeks) | Time from first dose of double blind medication (start of Period III) to occurrence of first OA flare. Flare was determined using pre-defined criteria, using an interactive voice response system |
| Proportion of Days Free From Osteoarthritis (OA) Flare | Period III (22 weeks) | Number of days subject was free from OA flare divided by number of days on study medication in Period III. Flare was determined using pre-defined criteria, using an interactive voice response system. |
| Proportion of Days in Osteoarthritis (OA) Flare | Period III (22 weeks) | Number of days subject was in OA flare divided by number of days on study medication in Period III. Subjects may have more than one flare. Flare was determined using pre-defined criteria, using an interactive voice response system. |
| Arthritis Pain Numerical Rating Scale (NRS) | Period III | Participant rated intensity of osteoarthritis pain on categorical scale from 0 (no pain) to 10 (worst pain). Scores analyzed as area under the curve (AUC) of participant's scores from each assessment in Period III. |
| Physician's Global Assessment of Arthritis at Final Visit | Period III (22 weeks) | Physician assessed each participant's disease symptoms on a categorical scale from 1 (very good) to 5 (very poor). |
| Total Rescue Medication Taken (Mean) | Period III (22 weeks) | Total amount of rescue medication (acetaminophen in milligrams \[mg\]) taken per month per participant |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in the Quality of Life Short Form-12v2 (SF-12v2) Scale Scores - All Assessments | Period III | SF-12v2 is a 12 item health survey covering 7 topics. Raw scores are transformed to a 0 to 100 scale. Higher scores indicate better state of health. Score at end of Period III minus score at start of Period III. |
| Serious Adverse Events in Open Label run-in Period | 2 weeks prior to double blind dosing | Serious adverse events occuring during the 2 week run-in period (Period II) when all participants were dosed with celecoxib 200 mg daily |
| Change in Medical Outcomes Study Sleep Scale - All Assessments | Period III | Subject assessment on 7 sleep associated categories. Raw scores are transformed to a 0-100 scale. Higher score indicates more of the outcome (e.g. more snoring, more adequate sleep). Score at end of Period III minus score at start of Period III. |
| Medical Outcomes Study Sleep Scale - Number of Participants With Optimal, Mixed and Not Optimal Sleep | Period III | Transformed score scale: 1=optimal; 0=not optimal; mixed = both optimal and non-optimal sleep during Period III |
Countries
Belgium, Brazil, Canada, Chile, Colombia, France, United Kingdom, United States
Participant flow
Recruitment details
111 centers in the Americas and Europe enrolled and treated subjects (2 centers in Belgium, 4 centers in Brazil, 20 centers in Canada, 5 centers in Chile, 5 centers in Columbia, 1 center in France, 15 centers in the United Kingdom, and 59 centers in the United States).
Pre-assignment details
17 participants completed Open-label run-in Period II and were randomized to Period III Double Blind but not treated.
Participants by arm
| Arm | Count |
|---|---|
| Celecoxib 200mg Continuous Use Double blind single dose of celecoxib 200 mg daily. Placebo used as flare medication when directed. | 431 |
| Celecoxib 200mg Intermittent Use Double blind placebo was taken once daily. Usual or intermittent use of celecoxib 200 mg daily as flare medication when directed. | 427 |
| Total | 858 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Period I | Did not enter Period II | 575 | 0 | 0 | 0 |
| Period II | Not Randomized into Period III | 0 | 322 | 0 | 0 |
| Period III | Adverse Event | 0 | 0 | 22 | 23 |
| Period III | Lack of Efficacy | 0 | 0 | 10 | 24 |
| Period III | Lost to Follow-up | 0 | 0 | 5 | 4 |
| Period III | Other | 0 | 0 | 23 | 34 |
| Period III | Withdrawal by Subject | 0 | 0 | 16 | 21 |
Baseline characteristics
| Characteristic | Celecoxib 200mg Continuous Use | Celecoxib 200mg Intermittent Use | Total |
|---|---|---|---|
| Age, Continuous | 58.5 years STANDARD_DEVIATION 10 | 58.7 years STANDARD_DEVIATION 9.6 | 58.6 years STANDARD_DEVIATION 9.8 |
| Sex: Female, Male Female | 317 Participants | 303 Participants | 620 Participants |
| Sex: Female, Male Male | 114 Participants | 124 Participants | 238 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 242 / — | 246 / — |
| serious Total, serious adverse events | 6 / — | 10 / — |
Outcome results
Primary
Number of Flare Events Per Time of Exposure to Study Medication
Number of flare events per month during Period III (calculated as number of flares divided by number of months participant was enrolled during Period III). Flare was determined using pre-defined criteria, using an interactive voice response system.
Time frame: Period III (22 weeks)
Population: Intent to treat (ITT) population included subjects who were randomized and received at least one dose of double blind study medication
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Celecoxib 200mg Continuous Use | Number of Flare Events Per Time of Exposure to Study Medication | 0.54 flare events per month | Standard Deviation 0.74 |
| Celecoxib 200mg Intermittent Use | Number of Flare Events Per Time of Exposure to Study Medication | 0.93 flare events per month | Standard Deviation 1.01 |
Comparison: Null hypothesis for primary outcome is that there is no difference in the number of flares observed between the 2 treatment arms of celecoxib 200mg continuous use and celecoxib 200mg intermittent use.~Sample size calculation: Sufficient number of participants were randomized to provide at least 80% power to detect an estimated effect size of 0.2 using a 2-sided t-test at a 0.05 significant level.p-value: <0.0001ANOVA
Secondary
Area Under the Curve (AUCs) of Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Scores
WOMAC assesses subject responses to 24 components regarding subscales of pain, stiffness and physical function (score range: 0=none to 4= extreme). Total score is sum of the 3 subscale scores. Scores analyzed as area under the curve (AUC) of participant's WOMAC scores from each assessment in Period III.
Time frame: Period III (22 weeks)
Population: Intent to treat (ITT) population included subjects who were randomized and received at least one dose of double blind study medication.~Number of subjects evaluable: continuous use Period III start n=428, end n=427; intermittent use Period III start n=424, end n=424
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Celecoxib 200mg Continuous Use | Area Under the Curve (AUCs) of Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Scores | Total WOMAC score | 604.9 scores on a scale * weeks | Standard Deviation 313.1 |
| Celecoxib 200mg Continuous Use | Area Under the Curve (AUCs) of Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Scores | WOMAC pain subscale | 119.2 scores on a scale * weeks | Standard Deviation 63.36 |
| Celecoxib 200mg Continuous Use | Area Under the Curve (AUCs) of Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Scores | WOMAC stiffness subscale | 54.5 scores on a scale * weeks | Standard Deviation 27.57 |
| Celecoxib 200mg Continuous Use | Area Under the Curve (AUCs) of Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Scores | WOMAC physical function subscale | 431.4 scores on a scale * weeks | Standard Deviation 229.38 |
| Celecoxib 200mg Intermittent Use | Area Under the Curve (AUCs) of Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Scores | WOMAC physical function subscale | 493.6 scores on a scale * weeks | Standard Deviation 230.74 |
| Celecoxib 200mg Intermittent Use | Area Under the Curve (AUCs) of Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Scores | Total WOMAC score | 693.6 scores on a scale * weeks | Standard Deviation 317.3 |
| Celecoxib 200mg Intermittent Use | Area Under the Curve (AUCs) of Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Scores | WOMAC stiffness subscale | 62.1 scores on a scale * weeks | Standard Deviation 27.7 |
| Celecoxib 200mg Intermittent Use | Area Under the Curve (AUCs) of Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Scores | WOMAC pain subscale | 138.4 scores on a scale * weeks | Standard Deviation 65.95 |
Comparison: WOMAC total scorep-value: <0.001ANCOVA
Comparison: WOMAC pain subscalep-value: <0.001ANCOVA
Comparison: WOMAC stiffness subscalep-value: <0.001ANCOVA
Comparison: WOMAC physical function subscalep-value: <0.001ANCOVA
Secondary
Arthritis Pain Numerical Rating Scale (NRS)
Participant rated intensity of osteoarthritis pain on categorical scale from 0 (no pain) to 10 (worst pain). Scores analyzed as area under the curve (AUC) of participant's scores from each assessment in Period III.
Time frame: Period III
Population: Intent to treat (ITT) population included subjects who were randomized and received at least one dose of double blind study medication.~These data are presented by the weeks from the start of Period II, 2 weeks before randomization. The weeks post-randomization, Period III, are different from the study weeks i.e. includes 2 weeks from Period II.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Celecoxib 200mg Continuous Use | Arthritis Pain Numerical Rating Scale (NRS) | Week 4 (n=415 cont; n=414 inter) | 81.7 scores on a scale * weeks | Standard Error 1.1 |
| Celecoxib 200mg Continuous Use | Arthritis Pain Numerical Rating Scale (NRS) | Week 8 (n=401 cont; n=395 inter) | 148.8 scores on a scale * weeks | Standard Error 2.6 |
| Celecoxib 200mg Continuous Use | Arthritis Pain Numerical Rating Scale (NRS) | Week 12 (n=383 cont; n=363 inter) | 212.6 scores on a scale * weeks | Standard Error 4.1 |
| Celecoxib 200mg Continuous Use | Arthritis Pain Numerical Rating Scale (NRS) | Week 16 (n=373 cont; n=339 inter) | 272.7 scores on a scale * weeks | Standard Error 5.9 |
| Celecoxib 200mg Continuous Use | Arthritis Pain Numerical Rating Scale (NRS) | Week 20 (n=362; n=323 inter) | 335.9 scores on a scale * weeks | Standard Error 7.8 |
| Celecoxib 200mg Continuous Use | Arthritis Pain Numerical Rating Scale (NRS) | Week 24 (n=350 cont; n=403 inter) | 378.1 scores on a scale * weeks | Standard Error 9.1 |
| Celecoxib 200mg Intermittent Use | Arthritis Pain Numerical Rating Scale (NRS) | Week 20 (n=362; n=323 inter) | 361.1 scores on a scale * weeks | Standard Error 7.8 |
| Celecoxib 200mg Intermittent Use | Arthritis Pain Numerical Rating Scale (NRS) | Week 4 (n=415 cont; n=414 inter) | 90.5 scores on a scale * weeks | Standard Error 1.1 |
| Celecoxib 200mg Intermittent Use | Arthritis Pain Numerical Rating Scale (NRS) | Week 16 (n=373 cont; n=339 inter) | 297.6 scores on a scale * weeks | Standard Error 5.9 |
| Celecoxib 200mg Intermittent Use | Arthritis Pain Numerical Rating Scale (NRS) | Week 8 (n=401 cont; n=395 inter) | 167.0 scores on a scale * weeks | Standard Error 2.6 |
| Celecoxib 200mg Intermittent Use | Arthritis Pain Numerical Rating Scale (NRS) | Week 24 (n=350 cont; n=403 inter) | 403.9 scores on a scale * weeks | Standard Error 9.2 |
| Celecoxib 200mg Intermittent Use | Arthritis Pain Numerical Rating Scale (NRS) | Week 12 (n=383 cont; n=363 inter) | 234.3 scores on a scale * weeks | Standard Error 4.1 |
Comparison: Week 4p-value: <0.001ANCOVA
Comparison: Week 8p-value: <0.001ANCOVA
Comparison: Week 12p-value: <0.001ANCOVA
Comparison: Week 16p-value: 0.003ANCOVA
Comparison: Week 20p-value: 0.022ANCOVA
Comparison: Week 24p-value: 0.047ANCOVA
Secondary
Change in Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Scores
Score at end of Period III minus score at start of Period III. WOMAC assesses subject responses to 24 components regarding subscales of pain, stiffness and physical function (score range: 0=none to 4= extreme). Total score is sum of the 3 subscale scores. Negative change indicates improvement.
Time frame: Period III (22 weeks)
Population: Intent to treat (ITT) population included subjects who were randomized and received at least one dose of double blind study medication. Number of subjects evaluable: continuous use Period III start n=428, end n=427; intermittent use Period III start n=424, end n=424
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Celecoxib 200mg Continuous Use | Change in Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Scores | Total WOMAC score | 1.60 scores on a scale | Standard Error 0.71 |
| Celecoxib 200mg Continuous Use | Change in Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Scores | WOMAC pain subscale | 0.37 scores on a scale | Standard Error 0.15 |
| Celecoxib 200mg Continuous Use | Change in Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Scores | WOMAC stiffness subscale | 0.12 scores on a scale | Standard Error 0.07 |
| Celecoxib 200mg Continuous Use | Change in Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Scores | WOMAC physical function subscale | 1.13 scores on a scale | Standard Error 0.51 |
| Celecoxib 200mg Intermittent Use | Change in Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Scores | WOMAC physical function subscale | 3.43 scores on a scale | Standard Error 0.51 |
| Celecoxib 200mg Intermittent Use | Change in Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Scores | Total WOMAC score | 4.99 scores on a scale | Standard Error 0.71 |
| Celecoxib 200mg Intermittent Use | Change in Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Scores | WOMAC stiffness subscale | 0.40 scores on a scale | Standard Error 0.07 |
| Celecoxib 200mg Intermittent Use | Change in Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Scores | WOMAC pain subscale | 1.18 scores on a scale | Standard Error 0.15 |
Comparison: Total WOMAC scorep-value: <0.001ANCOVA
Comparison: Total WOMAC score - Continuous use95% CI: [0.21, 2.99]
Comparison: Total WOMAC score - Intermittent use95% CI: [3.6, 6.38]
Comparison: WOMAC pain subscalep-value: <0.001ANCOVA
Comparison: WOMAC pain subscale - Continuous use95% CI: [0.06, 0.67]
Comparison: WOMAC pain subscale - Intermittent use95% CI: [0.88, 1.49]
Comparison: WOMAC stiffness subscalep-value: 0.004ANCOVA
Comparison: WOMAC stiffness subscale - Continuous use95% CI: [-0.02, 0.25]
Comparison: WOMAC stiffness subscale - Intermittent use95% CI: [0.26, 0.53]
Comparison: WOMAC physical function subscalep-value: 0.002ANCOVA
Comparison: WOMAC physical function subscale - Continuous use95% CI: [0.13, 2.14]
Comparison: WOMAC physical function subscale - Intermittent use95% CI: [2.42, 4.43]
Secondary
Days on Flare Medication
Number of days on flare medication per month per subject calculated as number of days on flare medication divided by the number of days on study medication in Period III
Time frame: Period III (22 weeks)
Population: Intent to treat (ITT) population included subjects who were randomized and received at least one dose of double blind study medication.~Subjects who did not take flare medication were calculated as 0 and included in the analysis.~Number of subjects taking flare medication: continuous use n=282; intermittent use n=339.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Celecoxib 200mg Continuous Use | Days on Flare Medication | 6.589 days on medication per month per subject | Standard Deviation 8.589 |
| Celecoxib 200mg Intermittent Use | Days on Flare Medication | 9.793 days on medication per month per subject | Standard Deviation 9.253 |
p-value: <0.0001ANOVA
Secondary
Patient's Global Assessment of Arthritis
Participant's response to question Considering all the ways the osteoarthritis in your hip or knee affects you, how are you doing today? on scale from 1 (very good) to 5 (very poor). Scores analyzed as area under the curve (AUC) of participant's scores from each assessment in Period III.
Time frame: Period III
Population: Intent to treat (ITT) population included subjects who were randomized and received at least one dose of double blind study medication.~These data are presented by the weeks from the start of Period II, 2 weeks before randomization. The weeks post-randomization, Period III, are different from the study weeks i.e. includes 2 weeks from Period II.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Celecoxib 200mg Continuous Use | Patient's Global Assessment of Arthritis | Week 4 (n=415 cont; n=414 inter) | 67.9 scores on a scale * weeks | Standard Error 0.68 |
| Celecoxib 200mg Continuous Use | Patient's Global Assessment of Arthritis | Week 8 (n=401 cont; n=395 inter) | 126.0 scores on a scale * weeks | Standard Error 1.55 |
| Celecoxib 200mg Continuous Use | Patient's Global Assessment of Arthritis | Week 12 (n=383 cont; n=363 inter) | 182.8 scores on a scale * weeks | Standard Error 2.48 |
| Celecoxib 200mg Continuous Use | Patient's Global Assessment of Arthritis | Week 16 (n=373 cont; n=339 inter) | 236.3 scores on a scale * weeks | Standard Error 3.59 |
| Celecoxib 200mg Continuous Use | Patient's Global Assessment of Arthritis | Week 20 (n=362 cont; n=323 inter) | 292.4 scores on a scale * weeks | Standard Error 4.83 |
| Celecoxib 200mg Continuous Use | Patient's Global Assessment of Arthritis | Week 24 (n=350 cont; n=309 inter) | 329.2 scores on a scale * weeks | Standard Error 5.75 |
| Celecoxib 200mg Intermittent Use | Patient's Global Assessment of Arthritis | Week 20 (n=362 cont; n=323 inter) | 293.8 scores on a scale * weeks | Standard Error 4.84 |
| Celecoxib 200mg Intermittent Use | Patient's Global Assessment of Arthritis | Week 4 (n=415 cont; n=414 inter) | 71.7 scores on a scale * weeks | Standard Error 0.69 |
| Celecoxib 200mg Intermittent Use | Patient's Global Assessment of Arthritis | Week 16 (n=373 cont; n=339 inter) | 241.2 scores on a scale * weeks | Standard Error 3.59 |
| Celecoxib 200mg Intermittent Use | Patient's Global Assessment of Arthritis | Week 8 (n=401 cont; n=395 inter) | 133.2 scores on a scale * weeks | Standard Error 1.56 |
| Celecoxib 200mg Intermittent Use | Patient's Global Assessment of Arthritis | Week 24 (n=350 cont; n=309 inter) | 328.9 scores on a scale * weeks | Standard Error 5.76 |
| Celecoxib 200mg Intermittent Use | Patient's Global Assessment of Arthritis | Week 12 (n=383 cont; n=363 inter) | 188.7 scores on a scale * weeks | Standard Error 2.48 |
Comparison: Week 4p-value: <0.001ANCOVA
Comparison: Week 8p-value: 0.001ANCOVA
Comparison: Week 12p-value: 0.096ANCOVA
Comparison: Week 16p-value: 0.338ANCOVA
Comparison: Week 20p-value: 0.832ANCOVA
Comparison: Week 24p-value: 0.972ANCOVA
Secondary
Physician's Global Assessment of Arthritis at Final Visit
Physician assessed each participant's disease symptoms on a categorical scale from 1 (very good) to 5 (very poor).
Time frame: Period III (22 weeks)
Population: Intent to treat (ITT) population included subjects who were randomized and received at least one dose of double blind study medication
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Celecoxib 200mg Continuous Use | Physician's Global Assessment of Arthritis at Final Visit | Grade 3 (fair) | 91 participants |
| Celecoxib 200mg Continuous Use | Physician's Global Assessment of Arthritis at Final Visit | Grade 4 (poor) | 23 participants |
| Celecoxib 200mg Continuous Use | Physician's Global Assessment of Arthritis at Final Visit | Grade 2 (good) | 242 participants |
| Celecoxib 200mg Continuous Use | Physician's Global Assessment of Arthritis at Final Visit | Grade 5 (very poor) | 2 participants |
| Celecoxib 200mg Continuous Use | Physician's Global Assessment of Arthritis at Final Visit | Grade 1 (very good) | 68 participants |
| Celecoxib 200mg Intermittent Use | Physician's Global Assessment of Arthritis at Final Visit | Grade 5 (very poor) | 2 participants |
| Celecoxib 200mg Intermittent Use | Physician's Global Assessment of Arthritis at Final Visit | Grade 1 (very good) | 39 participants |
| Celecoxib 200mg Intermittent Use | Physician's Global Assessment of Arthritis at Final Visit | Grade 2 (good) | 244 participants |
| Celecoxib 200mg Intermittent Use | Physician's Global Assessment of Arthritis at Final Visit | Grade 4 (poor) | 27 participants |
| Celecoxib 200mg Intermittent Use | Physician's Global Assessment of Arthritis at Final Visit | Grade 3 (fair) | 113 participants |
p-value: 0.0046Cochran-Mantel-Haenszel
Secondary
Proportion of Days Free From Osteoarthritis (OA) Flare
Number of days subject was free from OA flare divided by number of days on study medication in Period III. Flare was determined using pre-defined criteria, using an interactive voice response system.
Time frame: Period III (22 weeks)
Population: Intent to treat (ITT) population included subjects who were randomized and received at least one dose of double blind study medication
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Celecoxib 200mg Continuous Use | Proportion of Days Free From Osteoarthritis (OA) Flare | 0.77 proportion of days free from OA flare | Standard Deviation 0.28 |
| Celecoxib 200mg Intermittent Use | Proportion of Days Free From Osteoarthritis (OA) Flare | 0.67 proportion of days free from OA flare | Standard Deviation 0.3 |
p-value: <0.0001ANOVA
Secondary
Proportion of Days in Osteoarthritis (OA) Flare
Number of days subject was in OA flare divided by number of days on study medication in Period III. Subjects may have more than one flare. Flare was determined using pre-defined criteria, using an interactive voice response system.
Time frame: Period III (22 weeks)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Celecoxib 200mg Continuous Use | Proportion of Days in Osteoarthritis (OA) Flare | 0.23 proportion of days in OA flare | Standard Deviation 0.28 |
| Celecoxib 200mg Intermittent Use | Proportion of Days in Osteoarthritis (OA) Flare | 0.33 proportion of days in OA flare | Standard Deviation 0.3 |
p-value: <0.0001ANOVA
Secondary
Proportion of Days on Rescue Medication
Days on rescue medication divided by number of days on study medication in Period III
Time frame: Period III (22 weeks)
Population: Intent to treat (ITT) population included subjects who were randomized and received at least one dose of double blind study medication. Number of subjects taking rescue medication: continuous use n=220; intermittent use n=239.~Subjects who did not take rescue medication were calculated as 0 and included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Celecoxib 200mg Continuous Use | Proportion of Days on Rescue Medication | 0.044 proportion of days | Standard Deviation 0.102 |
| Celecoxib 200mg Intermittent Use | Proportion of Days on Rescue Medication | 0.069 proportion of days | Standard Deviation 0.121 |
p-value: 0.0012ANOVA
Secondary
Time to Occurrence of First Osteoarthritis (OA) Flare
Time from first dose of double blind medication (start of Period III) to occurrence of first OA flare. Flare was determined using pre-defined criteria, using an interactive voice response system
Time frame: Period III (22 weeks)
Population: Intent to treat (ITT) population included subjects who were randomized and received at least one dose of double blind study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Celecoxib 200mg Continuous Use | Time to Occurrence of First Osteoarthritis (OA) Flare | 16.0 days |
| Celecoxib 200mg Intermittent Use | Time to Occurrence of First Osteoarthritis (OA) Flare | 8.0 days |
Comparison: Kaplan-Meier analysisp-value: <0.0001Log Rank
Secondary
Total Rescue Medication Taken (Mean)
Total amount of rescue medication (acetaminophen in milligrams \[mg\]) taken per month per participant
Time frame: Period III (22 weeks)
Population: Intent to treat (ITT) population included subjects who were randomized and received at least one dose of double blind study medication.~Subjects who did not take rescue medication were assumed to have taken 0mg and were included in the analysis.~Number of subjects taking rescue medication: continuous use n=220; intermittent use n=239.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Celecoxib 200mg Continuous Use | Total Rescue Medication Taken (Mean) | 1566 mg taken per month per participant | Standard Deviation 4840 |
| Celecoxib 200mg Intermittent Use | Total Rescue Medication Taken (Mean) | 2428 mg taken per month per participant | Standard Deviation 4974 |
p-value: 0.0102ANOVA
Other Pre-specified
Change in Medical Outcomes Study Sleep Scale - All Assessments
Subject assessment on 7 sleep associated categories. Raw scores are transformed to a 0-100 scale. Higher score indicates more of the outcome (e.g. more snoring, more adequate sleep). Score at end of Period III minus score at start of Period III.
Time frame: Period III
Population: Intent to treat (ITT) population included subjects who were randomized and received at least one dose of double blind study medication. Subjects assessed per scale n=continuous use (cont); n=intermittent use (inter)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Celecoxib 200mg Continuous Use | Change in Medical Outcomes Study Sleep Scale - All Assessments | Sleep disturbance (n=415 cont; n=410 inter) | 0.5 scores on a scale | Standard Deviation 15.95 |
| Celecoxib 200mg Continuous Use | Change in Medical Outcomes Study Sleep Scale - All Assessments | Sleep adequacy (n=416 cont; n=413 inter) | 0.1 scores on a scale | Standard Deviation 24.47 |
| Celecoxib 200mg Continuous Use | Change in Medical Outcomes Study Sleep Scale - All Assessments | Awaken short of breath (n=417 cont; n=411 inter) | 1.9 scores on a scale | Standard Deviation 16.14 |
| Celecoxib 200mg Continuous Use | Change in Medical Outcomes Study Sleep Scale - All Assessments | Somnolence (n=416 cont; n=413 inter) | 1.4 scores on a scale | Standard Deviation 14.55 |
| Celecoxib 200mg Continuous Use | Change in Medical Outcomes Study Sleep Scale - All Assessments | Snoring (n=415 cont; n=412 inter) | 0.9 scores on a scale | Standard Deviation 22.36 |
| Celecoxib 200mg Continuous Use | Change in Medical Outcomes Study Sleep Scale - All Assessments | Quantity of sleep (n=417 cont; n=413 inter) | -0.1 scores on a scale | Standard Deviation 0.91 |
| Celecoxib 200mg Continuous Use | Change in Medical Outcomes Study Sleep Scale - All Assessments | Sleep problems index II (n=413 cont; n=408 inter) | 0.7 scores on a scale | Standard Deviation 12.29 |
| Celecoxib 200mg Continuous Use | Change in Medical Outcomes Study Sleep Scale - All Assessments | Sleep problems index I (n=416 cont; n=410 inter) | 0.9 scores on a scale | Standard Deviation 13.2 |
| Celecoxib 200mg Intermittent Use | Change in Medical Outcomes Study Sleep Scale - All Assessments | Sleep problems index II (n=413 cont; n=408 inter) | -0.1 scores on a scale | Standard Deviation 12.14 |
| Celecoxib 200mg Intermittent Use | Change in Medical Outcomes Study Sleep Scale - All Assessments | Sleep disturbance (n=415 cont; n=410 inter) | -1.4 scores on a scale | Standard Deviation 15.55 |
| Celecoxib 200mg Intermittent Use | Change in Medical Outcomes Study Sleep Scale - All Assessments | Snoring (n=415 cont; n=412 inter) | 0.7 scores on a scale | Standard Deviation 21.73 |
| Celecoxib 200mg Intermittent Use | Change in Medical Outcomes Study Sleep Scale - All Assessments | Awaken short of breath (n=417 cont; n=411 inter) | 1.1 scores on a scale | Standard Deviation 20 |
| Celecoxib 200mg Intermittent Use | Change in Medical Outcomes Study Sleep Scale - All Assessments | Quantity of sleep (n=417 cont; n=413 inter) | -0.1 scores on a scale | Standard Deviation 0.89 |
| Celecoxib 200mg Intermittent Use | Change in Medical Outcomes Study Sleep Scale - All Assessments | Sleep adequacy (n=416 cont; n=413 inter) | -1.3 scores on a scale | Standard Deviation 22.26 |
| Celecoxib 200mg Intermittent Use | Change in Medical Outcomes Study Sleep Scale - All Assessments | Somnolence (n=416 cont; n=413 inter) | 0.6 scores on a scale | Standard Deviation 13.7 |
| Celecoxib 200mg Intermittent Use | Change in Medical Outcomes Study Sleep Scale - All Assessments | Sleep problems index I (n=416 cont; n=410 inter) | 0.5 scores on a scale | Standard Deviation 13.18 |
Comparison: Sleep disturbancep-value: 0.2712ANCOVA
Comparison: Snoringp-value: 0.8737ANCOVA
Comparison: Awaken short of breathp-value: 0.7703ANCOVA
Comparison: Quantity of sleepp-value: 0.3769ANCOVA
Comparison: Sleep adequacyp-value: 0.4075ANCOVA
Comparison: Somnolencep-value: 0.5854ANCOVA
Comparison: Sleep problems index Ip-value: 0.8358ANCOVA
Comparison: Sleep problems index IIp-value: 0.5878ANCOVA
Other Pre-specified
Change in the Quality of Life Short Form-12v2 (SF-12v2) Scale Scores - All Assessments
SF-12v2 is a 12 item health survey covering 7 topics. Raw scores are transformed to a 0 to 100 scale. Higher scores indicate better state of health. Score at end of Period III minus score at start of Period III.
Time frame: Period III
Population: Intent to treat (ITT) population included subjects who were randomized and received at least one dose of double blind study medication.~Subjects assessed per scale n=continuous use (cont); n=intermittent use (inter)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Celecoxib 200mg Continuous Use | Change in the Quality of Life Short Form-12v2 (SF-12v2) Scale Scores - All Assessments | Physical function (n=417 cont; n=413 inter) | 1.8 scores on a scale | Standard Deviation 23.03 |
| Celecoxib 200mg Continuous Use | Change in the Quality of Life Short Form-12v2 (SF-12v2) Scale Scores - All Assessments | Role physical (n=416 cont; n=412 inter) | 3.5 scores on a scale | Standard Deviation 19.93 |
| Celecoxib 200mg Continuous Use | Change in the Quality of Life Short Form-12v2 (SF-12v2) Scale Scores - All Assessments | Bodily pain (n=417 cont; n=414 inter) | 3.8 scores on a scale | Standard Deviation 20.11 |
| Celecoxib 200mg Continuous Use | Change in the Quality of Life Short Form-12v2 (SF-12v2) Scale Scores - All Assessments | General health (n=417 cont; n=414 inter) | -0.3 scores on a scale | Standard Deviation 17.6 |
| Celecoxib 200mg Continuous Use | Change in the Quality of Life Short Form-12v2 (SF-12v2) Scale Scores - All Assessments | Vitality (n=416 cont; n=414 inter) | 0.3 scores on a scale | Standard Deviation 20.43 |
| Celecoxib 200mg Continuous Use | Change in the Quality of Life Short Form-12v2 (SF-12v2) Scale Scores - All Assessments | Social functioning (n=416 cont; n=414 inter) | -1.9 scores on a scale | Standard Deviation 20.16 |
| Celecoxib 200mg Continuous Use | Change in the Quality of Life Short Form-12v2 (SF-12v2) Scale Scores - All Assessments | Role emotional (n=417 cont; n=413 inter) | -0.7 scores on a scale | Standard Deviation 18.62 |
| Celecoxib 200mg Continuous Use | Change in the Quality of Life Short Form-12v2 (SF-12v2) Scale Scores - All Assessments | Mental health (n=416 cont; n=413 inter) | -0.9 scores on a scale | Standard Deviation 15.57 |
| Celecoxib 200mg Continuous Use | Change in the Quality of Life Short Form-12v2 (SF-12v2) Scale Scores - All Assessments | Physical component summary(n=416 cont;n=411 inter) | 9.0 scores on a scale | Standard Deviation 55.55 |
| Celecoxib 200mg Continuous Use | Change in the Quality of Life Short Form-12v2 (SF-12v2) Scale Scores - All Assessments | Mental component summary (n=416 cont;n=411 inter) | -3.1 scores on a scale | Standard Deviation 51.59 |
| Celecoxib 200mg Intermittent Use | Change in the Quality of Life Short Form-12v2 (SF-12v2) Scale Scores - All Assessments | Mental health (n=416 cont; n=413 inter) | -1.3 scores on a scale | Standard Deviation 16.05 |
| Celecoxib 200mg Intermittent Use | Change in the Quality of Life Short Form-12v2 (SF-12v2) Scale Scores - All Assessments | Physical function (n=417 cont; n=413 inter) | -3.2 scores on a scale | Standard Deviation 22.77 |
| Celecoxib 200mg Intermittent Use | Change in the Quality of Life Short Form-12v2 (SF-12v2) Scale Scores - All Assessments | Social functioning (n=416 cont; n=414 inter) | -3.5 scores on a scale | Standard Deviation 22.37 |
| Celecoxib 200mg Intermittent Use | Change in the Quality of Life Short Form-12v2 (SF-12v2) Scale Scores - All Assessments | Role physical (n=416 cont; n=412 inter) | -1.1 scores on a scale | Standard Deviation 20.07 |
| Celecoxib 200mg Intermittent Use | Change in the Quality of Life Short Form-12v2 (SF-12v2) Scale Scores - All Assessments | Mental component summary (n=416 cont;n=411 inter) | -10.5 scores on a scale | Standard Deviation 55.66 |
| Celecoxib 200mg Intermittent Use | Change in the Quality of Life Short Form-12v2 (SF-12v2) Scale Scores - All Assessments | Bodily pain (n=417 cont; n=414 inter) | -0.3 scores on a scale | Standard Deviation 21.56 |
| Celecoxib 200mg Intermittent Use | Change in the Quality of Life Short Form-12v2 (SF-12v2) Scale Scores - All Assessments | Role emotional (n=417 cont; n=413 inter) | -2.1 scores on a scale | Standard Deviation 19.8 |
| Celecoxib 200mg Intermittent Use | Change in the Quality of Life Short Form-12v2 (SF-12v2) Scale Scores - All Assessments | General health (n=417 cont; n=414 inter) | -0.8 scores on a scale | Standard Deviation 17.27 |
| Celecoxib 200mg Intermittent Use | Change in the Quality of Life Short Form-12v2 (SF-12v2) Scale Scores - All Assessments | Physical component summary(n=416 cont;n=411 inter) | -5.2 scores on a scale | Standard Deviation 57.48 |
| Celecoxib 200mg Intermittent Use | Change in the Quality of Life Short Form-12v2 (SF-12v2) Scale Scores - All Assessments | Vitality (n=416 cont; n=414 inter) | -3.5 scores on a scale | Standard Deviation 18.34 |
Comparison: Physical functionp-value: <0.0001ANCOVA
Comparison: Role physicalp-value: <0.0001ANCOVA
Comparison: Bodily painp-value: <0.0001ANCOVA
Comparison: General healthp-value: 0.3097ANCOVA
Comparison: Vitalityp-value: 0.0139ANCOVA
Comparison: Social functioningp-value: 0.1303ANCOVA
Comparison: Role emotionalp-value: 0.1404ANCOVA
Comparison: Mental healthp-value: 0.4015ANCOVA
Comparison: Physical component summaryp-value: <0.0001ANCOVA
Comparison: Mental component summaryp-value: 0.0301ANCOVA
Other Pre-specified
Medical Outcomes Study Sleep Scale - Number of Participants With Optimal, Mixed and Not Optimal Sleep
Transformed score scale: 1=optimal; 0=not optimal; mixed = both optimal and non-optimal sleep during Period III
Time frame: Period III
Population: Intent to treat (ITT) population included subjects who were randomized and received at least one dose of double blind study medication
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Celecoxib 200mg Continuous Use | Medical Outcomes Study Sleep Scale - Number of Participants With Optimal, Mixed and Not Optimal Sleep | Optimal (all scores are 1) | 139 participants |
| Celecoxib 200mg Continuous Use | Medical Outcomes Study Sleep Scale - Number of Participants With Optimal, Mixed and Not Optimal Sleep | Mixed (scores are both 1 and 0) | 166 participants |
| Celecoxib 200mg Continuous Use | Medical Outcomes Study Sleep Scale - Number of Participants With Optimal, Mixed and Not Optimal Sleep | Not optimal (all scores are 0) | 115 participants |
| Celecoxib 200mg Intermittent Use | Medical Outcomes Study Sleep Scale - Number of Participants With Optimal, Mixed and Not Optimal Sleep | Optimal (all scores are 1) | 123 participants |
| Celecoxib 200mg Intermittent Use | Medical Outcomes Study Sleep Scale - Number of Participants With Optimal, Mixed and Not Optimal Sleep | Mixed (scores are both 1 and 0) | 165 participants |
| Celecoxib 200mg Intermittent Use | Medical Outcomes Study Sleep Scale - Number of Participants With Optimal, Mixed and Not Optimal Sleep | Not optimal (all scores are 0) | 132 participants |
Comparison: Analysis across all 3 sleep scores for Period IIIp-value: 0.1437Cochran-Mantel-Haenszel
Other Pre-specified
Serious Adverse Events in Open Label run-in Period
Serious adverse events occuring during the 2 week run-in period (Period II) when all participants were dosed with celecoxib 200 mg daily
Time frame: 2 weeks prior to double blind dosing
Population: 1197 participants entered the open-label run-in (period II) to allow observation of successful treatment of an osteoarthritis flare. 875 participants were randomized to double blind treatment (period III). 322 participants were not randomized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Celecoxib 200mg Continuous Use | Serious Adverse Events in Open Label run-in Period | Anaemia | 1 participants |
| Celecoxib 200mg Continuous Use | Serious Adverse Events in Open Label run-in Period | Vitreous haemorrhage | 1 participants |