Osteoarthritis
Conditions
Brief summary
We will evaluate the efficacy of PN 400 and an active comparator in patients that have Osteoarthritis of the knee.
Detailed description
3-Month study in subjects 50 years and older with osteoarthritis of the knee. Assessments Western Ontario and McMaster Universities (WOMAC) pain and function and patient global assessment scales.
Interventions
DRUGPN 400 (VIMOVO)
500 mg naproxen/20 mg esomeprazole bid
DRUGcelebrex
200 mg celecoxib qd
OTHERPlacebo
sugar pill bid
DRUGRescue Antacid
Antacid Tablets
Sponsors
POZEN
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or non-pregnant female subjects50 years of age and older with a 6-month history of OA of the knee 2. Female subjects were eligible for participation in the study if they were of non-childbearing potential (i.e., physiologically incapable of becoming pregnant); or of childbearing potential, had a negative pregnancy test at Screening, and using adequate contraceptive methods. 3. Subjects were required to have been on a stable dose of NSAIDs, COX-2 inhibitors or other oral analgesic therapy for at least 6 weeks and required to continue treatment for 12 weeks. Current oral analgesic therapy was withdrawn at Screening. 4. Each subject was required to be able to understand and comply with study procedures required of a subject and was able and willing to provide written informed consent prior to any study procedures being performed. 5. Subjects were required to agree to keep physical activity at a stable level throughout the study. 6. Subjects were required to have symptomatic OA of the knee meeting American College of Rheumatology (ACR) criteria for clinical diagnosis of OA. 7. Subjects were required to have an ACR functional class rating of I, II or III. In addition, subjects meet the requirements for OA flare at the Baseline/ Randomization Visit.
Exclusion criteria
1. Subjects with rheumatoid arthritis or gout/pseudo-gout 2. Subjects with fibromyalgia syndrome 3. Acute joint trauma at the index joint within the 3 months prior to screen with active symptoms 4. Previous (in the past 12 months) or anticipated need for surgical or invasive procedure performed on the index joint during the study 5. Subject was currently taking or anticipated to take Coumadin®, warfarin, or lithium 6. History of hypersensitivity to esomeprazole or to another PPI 7. History of allergic reaction or intolerance to any NSAID (including aspirin) and/or subject had a history of NSAID-induced symptoms of asthma, rhinitis, and/or nasal polyps 8. History of allergic reactions to sulfonamides 9. Subjects with intra-articular or intramuscular corticosteroids or intra-articular hyaluronic acid injections within 8 weeks prior to randomization 10. Participation in any study of an investigational treatment in the 4 weeks before Screening 11. Presence of uncontrolled acute or chronic medical illness, e.g. morbid obesity, GI disorder, diabetes, active GI disease, chronic or acute renal or hepatic disorder, depression and/or infection, etc, that would endanger a subject if the subject were to participate in the study 12. GI disorder (e.g., severe erosive esophagitis, Zollinger Ellison syndrome) or surgery leading to impaired drug absorption 13. Peptic ulcer disease within 6 months prior to Screening 14. Evidence of uncontrolled, or unstable cardio- or cerebrovascular disorder, which in the investigator's opinion would have endangered a subject if the subject were to participate in the study 15. Schizophrenia or bipolar disorder 16. Subjects who had started physical therapy on the index joint less than 6 weeks prior to study Screening 17. Use of any excluded concomitant medication 18. A recent history (in the past 3 months) suggestive of alcohol or drug abuse or dependence, including overuse/abuse of narcotics for management of pain 19. Serious blood coagulation disorder including use of systemic anti-coagulants 20. Screening laboratory value for alanine aminotransferase, aspartate aminotransferase greater than 2 times the upper limit of normal 21. Estimated creatinine clearance less than 30 ml/min 22. Other than noted specifically, any Screening laboratory value that was clinically significant in the investigator's opinion and would have endangered a subject if the subjects were to participate in the study 23. History of malignancy, treated or untreated, within the past 5 years, with the exception of successfully treated basal cell or squamous cell carcinoma of the skin 24. Previous participation in another PN 400 clinical research trial 25. Subjects who were employees of the research facility or who were in some way under the supervision of the principal investigator for this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Western Ontario and McMaster Universities (WOMAC) Pain Questionnaire Subscore From Baseline | Baseline and 12 Weeks | Western Ontario and McMaster Universities (WOMAC) pain questionnaire has 5 questions on pain all use visual analog scale (VAS) of 100 mm, with 0 mm being no pain and 100 mm being extreme pain. The outcome measures a change in WOMAC pain at 12 weeks from baseline (in mm). WOMAC is a self-administered, patient-reported health status questionnaire designed to capture elements of pain, stiffness and physical disability in patients with OA of the knee and/or hip joints. It consists of 24 questions (5 questions about pain, 2 on stiffness and 17 about physical function). |
| Change in Western Ontario and McMaster Universities (WOMAC) Function Questionnaire Subscore From Baseline | 12 Weeks | WOMAC function questionnaire (VAS). The 17 questions about function all use visual analog scale (VAS) of 100 mm; 0 mm being no pain and 100 mm being extreme pain. The outcome measures a change in WOMAC pain from baseline (in mm). The Western Ontario and McMaster Universities (WOMAC) is a self-administered, patient-reported health status questionnaire that is designed to capture elements of pain, stiffness and physical disability in patients with OA of the knee and/or hip joints. The index consists of 24 questions (5 questions about pain, 2 on stiffness and 17 about physical function). |
| Change in Patient Global Assessment (PGA) Subscore From Baseline | 12 Weeks | PGA questionnaire. The patient global assessment (PGA) question asks about how the subject is doing considering his/her arthritis and is measured by a visual analog scale (VAS); 0 mm (very poor) 100 mm (excellent). The outcome measures a change from baseline PGA in mm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Patient Global Assessment (PGA) Subscore From Baseline | Week 6 | PGA questionnaire. The patient global assessment (PGA) question asks about how the subject is doing considering his/her arthritis and is measured by a visual analog scale (VAS); 0 mm (very poor) 100 mm (excellent). The outcome measures a change from baseline PGA in mm. |
| Antacid Tablet Use | 12 weeks | Tablet pill count |
| Modified Severity of Dyspepsia Assessment (mSODA) | 12 weeks | Change from Baseline in the Modified Severity of Dyspepsia Assessment (mSODA) average daily pain intensity converted total score at Week 12. The mSODA instruments consists of 6 questions about abdominal discomfort during the past 24 hours, with a converted score of 2 through 47. Lower score equals less pain. |
| Mean Change From Baseline in American Pain Society Patient Outcome Questionnaire (APS-POQ)Total Interference Caused by Pain. | Baseline and Day 7 | For APS-POQ score is the change from Baseline scores calculated for each subject through Day 7. Scale 0 through 70, where 0=no pain interference and 70=complete interference. |
| Number of Participants Reporting Pre-specified Non-steroidal Antiinflammatory Drug-associated Upper Gastrointestinal (UGI) Symptoms | daily during 12 weeks | Number of participants reporting pre-specified non-steroidal antiinflammatory drug-associated (NSAID) upper gastrointestinal (UGI) symptoms. Pre-specified NSAID-associated UGI symptoms include adverse events such as dyspepsia, abdominal pain or discomfort, nausea, vomiting. |
| The Number of Subjects Who Discontinued From the Study Due to Any Pre-specified Non-steroidal Antiinflammatory Drug-associated Upper Gastrointestinal Adverse Event | daily during 12 weeks | The number of subjects who discontinued from the study due to any pre-specified non-steroidal antiinflammatory drug (NSAID)-associated upper gastrointestinal (UGI) adverse event (as classified by MedDRA). Pre-specified NSAID-associated UGI symptoms include adverse events such as dyspepsia, abdominal pain or discomfort, nausea, vomiting. |
| Percent of Days With no Heartburn (Heartburn Resolution) | 12 weeks | During 12 weeks, daily heartburn question with ratings none, mild, moderate, or severe. Percent of days with Heartburn resolution (heartburn is none). |
| Change in Western Ontario and McMaster Universities (WOMAC) Pain Questionnaire Subscore From Baseline | Week 6 | Western Ontario and McMaster Universities (WOMAC) pain questionnaire has 5 questions on pain all use visual analog scale (VAS) of 100 mm, with 0 mm being no pain and 100 mm being extreme pain. The outcome measures a change in WOMAC pain at 6 weeks from baseline (in mm). WOMAC is a self-administered, patient-reported health status questionnaire designed to capture elements of pain, stiffness and physical disability in patients with OA of the knee and/or hip joints. It consists of 24 questions (5 questions about pain, 2 on stiffness and 17 about physical function). |
| Change in Western Ontario and McMaster Universities (WOMAC) Function Questionnaire Subscore From Baseline | Week 6 | WOMAC function questionnaire (VAS). The 17 questions about function all use visual analog scale (VAS) of 100 mm; 0 mm being no pain and 100 mm being extreme pain. The outcome measures a change in WOMAC pain from baseline (in mm). The Western Ontario and McMaster Universities (WOMAC) is a self-administered, patient-reported health status questionnaire that is designed to capture elements of pain, stiffness and physical disability in patients with OA of the knee and/or hip joints. The index consists of 24 questions (5 questions about pain, 2 on stiffness and 17 about physical function). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| (PN 400 (VIMOVO) Twice Daily) PN 400: 500 mg naproxen/20 mg esomeprazole | 243 |
| (Celebrex 200 mg Once Daily) Celecoxib 200 mg (Celebrex) taken once daily | 245 |
| (Placebo Twice Daily) placebo (sugar pill) dosed twice daily (bid) | 122 |
| Total | 610 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 16 | 22 | 6 |
| Overall Study | Lost to Follow-up | 3 | 3 | 1 |
| Overall Study | Other | 4 | 7 | 2 |
| Overall Study | Withdrawal by Subject | 17 | 25 | 15 |
Baseline characteristics
| Characteristic | (PN 400 (VIMOVO) Twice Daily) | (Celebrex 200 mg Once Daily) | (Placebo Twice Daily) | Total |
|---|---|---|---|---|
| Age Continuous | 61.7 years STANDARD_DEVIATION 8.6 | 62.3 years STANDARD_DEVIATION 8.4 | 61.6 years STANDARD_DEVIATION 8.7 | 61.9 years STANDARD_DEVIATION 8.5 |
| Sex: Female, Male Female | 158 Participants | 153 Participants | 77 Participants | 388 Participants |
| Sex: Female, Male Male | 85 Participants | 92 Participants | 45 Participants | 222 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 | 111 / 243 | 107 / 245 | 53 / 122 |
| serious Total, serious adverse events | 3 / 243 | 3 / 245 | 1 / 122 |
Outcome results
Primary
Change in Patient Global Assessment (PGA) Subscore From Baseline
PGA questionnaire. The patient global assessment (PGA) question asks about how the subject is doing considering his/her arthritis and is measured by a visual analog scale (VAS); 0 mm (very poor) 100 mm (excellent). The outcome measures a change from baseline PGA in mm.
Time frame: 12 Weeks
Population: Analysis Population: Baseline + took \>= 1 dose + \>= 1 post-baseline PGA efficacy evaluation (intent-to-treat population). Used Last Observation Carried Forward
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| (PN 400 (VIMOVO) Twice Daily) | Change in Patient Global Assessment (PGA) Subscore From Baseline | 27.7 mm | Standard Deviation 34.8 |
| (Celebrex 200 mg Once Daily) | Change in Patient Global Assessment (PGA) Subscore From Baseline | 26.4 mm | Standard Deviation 30.3 |
| (Placebo Twice Daily) | Change in Patient Global Assessment (PGA) Subscore From Baseline | 22.4 mm | Standard Deviation 31.3 |
95% CI: [-1.41, 8.31]ANCOVA
Primary
Change in Western Ontario and McMaster Universities (WOMAC) Function Questionnaire Subscore From Baseline
WOMAC function questionnaire (VAS). The 17 questions about function all use visual analog scale (VAS) of 100 mm; 0 mm being no pain and 100 mm being extreme pain. The outcome measures a change in WOMAC pain from baseline (in mm). The Western Ontario and McMaster Universities (WOMAC) is a self-administered, patient-reported health status questionnaire that is designed to capture elements of pain, stiffness and physical disability in patients with OA of the knee and/or hip joints. The index consists of 24 questions (5 questions about pain, 2 on stiffness and 17 about physical function).
Time frame: 12 Weeks
Population: Analysis Population: Baseline + took \>= 1 dose + \>= 1 post-baseline WOMAC efficacy evaluation (intent-to-treat population). Used Last Observation Carried Forward
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| (PN 400 (VIMOVO) Twice Daily) | Change in Western Ontario and McMaster Universities (WOMAC) Function Questionnaire Subscore From Baseline | -38.7 mm | Standard Deviation 27.2 |
| (Celebrex 200 mg Once Daily) | Change in Western Ontario and McMaster Universities (WOMAC) Function Questionnaire Subscore From Baseline | -37.7 mm | Standard Deviation 27.5 |
| (Placebo Twice Daily) | Change in Western Ontario and McMaster Universities (WOMAC) Function Questionnaire Subscore From Baseline | -30.9 mm | Standard Deviation 28 |
95% CI: [-6.82, 2.6]ANCOVA
Primary
Change in Western Ontario and McMaster Universities (WOMAC) Pain Questionnaire Subscore From Baseline
Western Ontario and McMaster Universities (WOMAC) pain questionnaire has 5 questions on pain all use visual analog scale (VAS) of 100 mm, with 0 mm being no pain and 100 mm being extreme pain. The outcome measures a change in WOMAC pain at 12 weeks from baseline (in mm). WOMAC is a self-administered, patient-reported health status questionnaire designed to capture elements of pain, stiffness and physical disability in patients with OA of the knee and/or hip joints. It consists of 24 questions (5 questions about pain, 2 on stiffness and 17 about physical function).
Time frame: Baseline and 12 Weeks
Population: Analysis Population: Baseline + took \>= 1 dose + \>= 1 post-baseline WOMAC efficacy evaluation (intent-to-treat population). Used Last Observation Carried Forward
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| (PN 400 (VIMOVO) Twice Daily) | Change in Western Ontario and McMaster Universities (WOMAC) Pain Questionnaire Subscore From Baseline | -44.1 mm | Standard Deviation 27.5 |
| (Celebrex 200 mg Once Daily) | Change in Western Ontario and McMaster Universities (WOMAC) Pain Questionnaire Subscore From Baseline | -43.6 mm | Standard Deviation 25.2 |
| (Placebo Twice Daily) | Change in Western Ontario and McMaster Universities (WOMAC) Pain Questionnaire Subscore From Baseline | -37.3 mm | Standard Deviation 26.1 |
95% CI: [-5.94, 3.34]ANCOVA
Secondary
Antacid Tablet Use
Tablet pill count
Time frame: 12 weeks
Population: Intent to treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| (PN 400 (VIMOVO) Twice Daily) | Antacid Tablet Use | 13.4 Tablets per subject | Standard Deviation 31.3 |
| (Celebrex 200 mg Once Daily) | Antacid Tablet Use | 20.9 Tablets per subject | Standard Deviation 66 |
| (Placebo Twice Daily) | Antacid Tablet Use | 27.3 Tablets per subject | Standard Deviation 86.9 |
Secondary
Change in Patient Global Assessment (PGA) Subscore From Baseline
PGA questionnaire. The patient global assessment (PGA) question asks about how the subject is doing considering his/her arthritis and is measured by a visual analog scale (VAS); 0 mm (very poor) 100 mm (excellent). The outcome measures a change from baseline PGA in mm.
Time frame: Week 6
Population: Intent to treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| (PN 400 (VIMOVO) Twice Daily) | Change in Patient Global Assessment (PGA) Subscore From Baseline | 25.9 mm | Standard Deviation 34.5 |
| (Celebrex 200 mg Once Daily) | Change in Patient Global Assessment (PGA) Subscore From Baseline | 24.4 mm | Standard Deviation 29.3 |
| (Placebo Twice Daily) | Change in Patient Global Assessment (PGA) Subscore From Baseline | 22.3 mm | Standard Deviation 29.9 |
Secondary
Change in Western Ontario and McMaster Universities (WOMAC) Function Questionnaire Subscore From Baseline
WOMAC function questionnaire (VAS). The 17 questions about function all use visual analog scale (VAS) of 100 mm; 0 mm being no pain and 100 mm being extreme pain. The outcome measures a change in WOMAC pain from baseline (in mm). The Western Ontario and McMaster Universities (WOMAC) is a self-administered, patient-reported health status questionnaire that is designed to capture elements of pain, stiffness and physical disability in patients with OA of the knee and/or hip joints. The index consists of 24 questions (5 questions about pain, 2 on stiffness and 17 about physical function).
Time frame: Week 6
Population: Intent to treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| (PN 400 (VIMOVO) Twice Daily) | Change in Western Ontario and McMaster Universities (WOMAC) Function Questionnaire Subscore From Baseline | -38.5 mm | Standard Deviation 26.2 |
| (Celebrex 200 mg Once Daily) | Change in Western Ontario and McMaster Universities (WOMAC) Function Questionnaire Subscore From Baseline | -34.6 mm | Standard Deviation 26.3 |
| (Placebo Twice Daily) | Change in Western Ontario and McMaster Universities (WOMAC) Function Questionnaire Subscore From Baseline | -29.0 mm | Standard Deviation 26.4 |
Secondary
Change in Western Ontario and McMaster Universities (WOMAC) Pain Questionnaire Subscore From Baseline
Western Ontario and McMaster Universities (WOMAC) pain questionnaire has 5 questions on pain all use visual analog scale (VAS) of 100 mm, with 0 mm being no pain and 100 mm being extreme pain. The outcome measures a change in WOMAC pain at 6 weeks from baseline (in mm). WOMAC is a self-administered, patient-reported health status questionnaire designed to capture elements of pain, stiffness and physical disability in patients with OA of the knee and/or hip joints. It consists of 24 questions (5 questions about pain, 2 on stiffness and 17 about physical function).
Time frame: Week 6
Population: Intent to treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| (PN 400 (VIMOVO) Twice Daily) | Change in Western Ontario and McMaster Universities (WOMAC) Pain Questionnaire Subscore From Baseline | -44.3 mm | Standard Deviation 25.7 |
| (Celebrex 200 mg Once Daily) | Change in Western Ontario and McMaster Universities (WOMAC) Pain Questionnaire Subscore From Baseline | -39.6 mm | Standard Deviation 25.7 |
| (Placebo Twice Daily) | Change in Western Ontario and McMaster Universities (WOMAC) Pain Questionnaire Subscore From Baseline | -33.9 mm | Standard Deviation 25.4 |
Secondary
Mean Change From Baseline in American Pain Society Patient Outcome Questionnaire (APS-POQ)Total Interference Caused by Pain.
For APS-POQ score is the change from Baseline scores calculated for each subject through Day 7. Scale 0 through 70, where 0=no pain interference and 70=complete interference.
Time frame: Baseline and Day 7
Population: Intent to treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| (PN 400 (VIMOVO) Twice Daily) | Mean Change From Baseline in American Pain Society Patient Outcome Questionnaire (APS-POQ)Total Interference Caused by Pain. | -18.8 Units on a scale | Standard Deviation 15.8 |
| (Celebrex 200 mg Once Daily) | Mean Change From Baseline in American Pain Society Patient Outcome Questionnaire (APS-POQ)Total Interference Caused by Pain. | -16.6 Units on a scale | Standard Deviation 14.8 |
| (Placebo Twice Daily) | Mean Change From Baseline in American Pain Society Patient Outcome Questionnaire (APS-POQ)Total Interference Caused by Pain. | -11.6 Units on a scale | Standard Deviation 12.3 |
Secondary
Modified Severity of Dyspepsia Assessment (mSODA)
Change from Baseline in the Modified Severity of Dyspepsia Assessment (mSODA) average daily pain intensity converted total score at Week 12. The mSODA instruments consists of 6 questions about abdominal discomfort during the past 24 hours, with a converted score of 2 through 47. Lower score equals less pain.
Time frame: 12 weeks
Population: intent to treat with last observation carried forward
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| (PN 400 (VIMOVO) Twice Daily) | Modified Severity of Dyspepsia Assessment (mSODA) | -4.5 Scores on a scale | Standard Deviation 10 |
| (Celebrex 200 mg Once Daily) | Modified Severity of Dyspepsia Assessment (mSODA) | -3.3 Scores on a scale | Standard Deviation 9 |
| (Placebo Twice Daily) | Modified Severity of Dyspepsia Assessment (mSODA) | -3.5 Scores on a scale | Standard Deviation 9.8 |
Secondary
Number of Participants Reporting Pre-specified Non-steroidal Antiinflammatory Drug-associated Upper Gastrointestinal (UGI) Symptoms
Number of participants reporting pre-specified non-steroidal antiinflammatory drug-associated (NSAID) upper gastrointestinal (UGI) symptoms. Pre-specified NSAID-associated UGI symptoms include adverse events such as dyspepsia, abdominal pain or discomfort, nausea, vomiting.
Time frame: daily during 12 weeks
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| (PN 400 (VIMOVO) Twice Daily) | Number of Participants Reporting Pre-specified Non-steroidal Antiinflammatory Drug-associated Upper Gastrointestinal (UGI) Symptoms | 46 participants |
| (Celebrex 200 mg Once Daily) | Number of Participants Reporting Pre-specified Non-steroidal Antiinflammatory Drug-associated Upper Gastrointestinal (UGI) Symptoms | 53 participants |
| (Placebo Twice Daily) | Number of Participants Reporting Pre-specified Non-steroidal Antiinflammatory Drug-associated Upper Gastrointestinal (UGI) Symptoms | 25 participants |
Secondary
Percent of Days With no Heartburn (Heartburn Resolution)
During 12 weeks, daily heartburn question with ratings none, mild, moderate, or severe. Percent of days with Heartburn resolution (heartburn is none).
Time frame: 12 weeks
Population: Intent to treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| (PN 400 (VIMOVO) Twice Daily) | Percent of Days With no Heartburn (Heartburn Resolution) | 78.4 percent days | Standard Deviation 34.5 |
| (Celebrex 200 mg Once Daily) | Percent of Days With no Heartburn (Heartburn Resolution) | 72.1 percent days | Standard Deviation 35.8 |
| (Placebo Twice Daily) | Percent of Days With no Heartburn (Heartburn Resolution) | 71.1 percent days | Standard Deviation 39 |
Secondary
The Number of Subjects Who Discontinued From the Study Due to Any Pre-specified Non-steroidal Antiinflammatory Drug-associated Upper Gastrointestinal Adverse Event
The number of subjects who discontinued from the study due to any pre-specified non-steroidal antiinflammatory drug (NSAID)-associated upper gastrointestinal (UGI) adverse event (as classified by MedDRA). Pre-specified NSAID-associated UGI symptoms include adverse events such as dyspepsia, abdominal pain or discomfort, nausea, vomiting.
Time frame: daily during 12 weeks
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| (PN 400 (VIMOVO) Twice Daily) | The Number of Subjects Who Discontinued From the Study Due to Any Pre-specified Non-steroidal Antiinflammatory Drug-associated Upper Gastrointestinal Adverse Event | 2 participants |
| (Celebrex 200 mg Once Daily) | The Number of Subjects Who Discontinued From the Study Due to Any Pre-specified Non-steroidal Antiinflammatory Drug-associated Upper Gastrointestinal Adverse Event | 9 participants |
| (Placebo Twice Daily) | The Number of Subjects Who Discontinued From the Study Due to Any Pre-specified Non-steroidal Antiinflammatory Drug-associated Upper Gastrointestinal Adverse Event | 3 participants |