Efficacy Study of PN400 (VIMOVO) Twice Daily and Celebrex Once Daily in Patients With Osteoarthritis

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

We will evaluate the efficacy of PN400 and an active comparator in patients that have Osteoarthritis of the knee.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis
• Intervention / Treatment: Drug: PN 400 (VIMOVO); Drug: Rescue Antacid; Drug: celebrex; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 614
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27517
      • Pozen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 46 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Current oral analgesic therapy was withdrawn at Screening.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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ARM 1 PN 400 (VIMOVO); PN400: 500 mg naproxen/20 mg esomeprazole	Drug: PN 400 (VIMOVO); 500 mg naproxen/20 mg esomeprazole bid; Other Names: PN 400; Drug: Rescue Antacid; Antacid Tablets
Active Comparator: Arm 2 (celebrex); Celecoxib 200 mg	Drug: Rescue Antacid; Antacid Tablets; Drug: celebrex; 200 mg celecoxib qd
Placebo Comparator: Arm 3 (placebo); sugar pill	Drug: Rescue Antacid; Antacid Tablets; Drug: Placebo; sugar pill bid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	Baseline and 12 weeks
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).	12 weeks
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.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
American Pain Society Patient Outcome Questionnaire (APS-POQ)Total Interference Caused by Pain.	Mean change from Baseline scores calculated for each subject through Day 7. Scale 0 through 70, where 0=no pain interference and 70=complete interference.	Baseline and Day 7
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).	Week 6
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).	Week 6
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.	Week 6
Antacid Tablet Use	Tablet pill count	12 weeks
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.	Baseline to 12 weeks
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).	12 weeks
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.	daily during 12 weeks
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.	daily during 12 weeks

Collaborators and Investigators

• Sponsor: POZEN

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): January 1, 2009

Study Registration Dates

• First Submitted: April 18, 2008
• First Submitted That Met QC Criteria: April 22, 2008
• First Posted (Estimate): April 23, 2008

Study Record Updates

• Last Update Posted (Estimate): February 27, 2012
• Last Update Submitted That Met QC Criteria: January 20, 2012
• Last Verified: January 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Gastrointestinal Agents; Cyclooxygenase 2 Inhibitors; Celecoxib; Antacids
• Other Study ID Numbers: PN400-307