Clinical trial NCT00665431: Efficacy Study of PN400 (VIMOVO) Twice Daily and Celebrex Once Daily in Patients With Osteoarthritis
Official title: Randomized, Double-Blind, Parallel Group, Placebo-Controlled Multi-Center Study Evaluating the Efficacy of PN400 (VIMOVO) Twice Daily (Bid) and Celecoxib Once Daily (qd) in Patients With Osteoarthritis of the Knee
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Osteoarthritis
Lead sponsor: POZEN
Sponsor class: INDUSTRY
First posted: 2008-04-23
Enrollment: 610
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 Current oral analgesic therapy was withdrawn at Screening.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

Primary outcomes:
measure: Change in Western Ontario and McMaster Universities (WOMAC) Pain Questionnaire Subscore From Baseline
timeFrame: Baseline and 12 Weeks
measure: Change in Western Ontario and McMaster Universities (WOMAC) Function Questionnaire Subscore From Baseline
timeFrame: 12 Weeks
measure: Change in Patient Global Assessment (PGA) Subscore From Baseline
timeFrame: 12 Weeks
Secondary outcomes:
measure: Mean Change From Baseline in American Pain Society Patient Outcome Questionnaire (APS-POQ)Total Interference Caused by Pain.
timeFrame: Baseline and Day 7
measure: Change in Western Ontario and McMaster Universities (WOMAC) Pain Questionnaire Subscore From Baseline
timeFrame: Week 6
measure: Change in Western Ontario and McMaster Universities (WOMAC) Function Questionnaire Subscore From Baseline
timeFrame: Week 6
measure: Change in Patient Global Assessment (PGA) Subscore From Baseline
timeFrame: Week 6
measure: Antacid Tablet Use
timeFrame: 12 weeks
measure: Modified Severity of Dyspepsia Assessment (mSODA)
timeFrame: 12 weeks
measure: Percent of Days With no Heartburn (Heartburn Resolution)
timeFrame: 12 weeks
measure: Number of Participants Reporting Pre-specified Non-steroidal Antiinflammatory Drug-associated Upper Gastrointestinal (UGI) Symptoms
timeFrame: daily during 12 weeks
measure: The Number of Subjects Who Discontinued From the Study Due to Any Pre-specified Non-steroidal Antiinflammatory Drug-associated Upper Gastrointestinal Adverse Event
timeFrame: daily during 12 weeks
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: POZEN
state: North Carolina
Study officials:
affiliation: POZEN
name: Everardus Orlemans, PhD
role: STUDY_CHAIR
References:
citation: Holt RJ, Fort JG, Grahn AY, Kent JD, Bello AE. Onset and durability of pain relief in knee osteoarthritis: Pooled results from two placebo trials of naproxen/esomeprazole combination and celecoxib. Phys Sportsmed. 2015 Jul;43(3):200-12. doi: 10.1080/00913847.2015.1074852. Epub 2015 Aug 3.
citation: Hochberg MC, Fort JG, Svensson O, Hwang C, Sostek M. Fixed-dose combination of enteric-coated naproxen and immediate-release esomeprazole has comparable efficacy to celecoxib for knee osteoarthritis: two randomized trials. Curr Med Res Opin. 2011 Jun;27(6):1243-53. doi: 10.1185/03007995.2011.580340. Epub 2011 Apr 28.