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

Purpose

We will evaluate the efficacy of PN 400 and an active comparator in patients that have Osteoarthritis of the knee.

Condition	Intervention	Phase
Osteoarthritis	Drug: PN 400 (VIMOVO) Drug: celebrex Other: Placebo Drug: Rescue Antacid	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Osteoarthritis

Drug Information available for: Celecoxib

U.S. FDA Resources

Further study details as provided by POZEN:

Primary Outcome Measures:

Change in Western Ontario and McMaster Universities (WOMAC) Pain Questionnaire Subscore From Baseline [ Time Frame: Baseline and 12 Weeks ] [ Designated as safety issue: No ]
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 [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
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 [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
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 Outcome Measures:

Mean Change From Baseline in American Pain Society Patient Outcome Questionnaire (APS-POQ)Total Interference Caused by Pain. [ Time Frame: Baseline and Day 7 ] [ Designated as safety issue: No ]
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.
Change in Western Ontario and McMaster Universities (WOMAC) Pain Questionnaire Subscore From Baseline [ Time Frame: Week 6 ] [ Designated as safety issue: No ]
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 [ Time Frame: Week 6 ] [ Designated as safety issue: No ]
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 [ Time Frame: Week 6 ] [ Designated as safety issue: No ]
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 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Tablet pill count
Modified Severity of Dyspepsia Assessment (mSODA) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
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.
Percent of Days With no Heartburn (Heartburn Resolution) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
During 12 weeks, daily heartburn question with ratings none, mild, moderate, or severe. Percent of days with Heartburn resolution (heartburn is none).
Number of Participants Reporting Pre-specified Non-steroidal Antiinflammatory Drug-associated Upper Gastrointestinal (UGI) Symptoms [ Time Frame: daily during 12 weeks ] [ Designated as safety issue: No ]
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 [ Time Frame: daily during 12 weeks ] [ Designated as safety issue: Yes ]
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.

Enrollment:	610
Study Start Date:	April 2008
Study Completion Date:	January 2009
Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Arm 1 PN 400 (VIMOVO) PN400: 500 mg naproxen/20 mg esomeprazole bid	Drug: PN 400 (VIMOVO) 500 mg naproxen/20 mg esomeprazole bid Other Name: PN400 Drug: Rescue Antacid Antacid Tablets
Active Comparator: Arm 2 (Celebrex) Celecoxib 200 mg	Drug: celebrex 200 mg celecoxib qd Other Name: Celebrex Drug: Rescue Antacid Antacid Tablets
Placebo Comparator: Arm 3 (Placebo) sugar pill	Other: Placebo sugar pill bid Other Name: Placebo Drug: Rescue Antacid Antacid Tablets

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

Ages Eligible for Study:	50 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria

Male or non-pregnant female subjects50 years of age and older with a 6-month history of OA of the knee
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.
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.
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.
Subjects were required to agree to keep physical activity at a stable level throughout the study.
Subjects were required to have symptomatic OA of the knee meeting American College of Rheumatology (ACR) criteria for clinical diagnosis of OA.
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

Subjects with rheumatoid arthritis or gout/pseudo-gout
Subjects with fibromyalgia syndrome
Acute joint trauma at the index joint within the 3 months prior to screen with active symptoms
Previous (in the past 12 months) or anticipated need for surgical or invasive procedure performed on the index joint during the study
Subject was currently taking or anticipated to take Coumadin®, warfarin, or lithium
History of hypersensitivity to esomeprazole or to another PPI
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
History of allergic reactions to sulfonamides
Subjects with intra-articular or intramuscular corticosteroids or intra-articular hyaluronic acid injections within 8 weeks prior to randomization
Participation in any study of an investigational treatment in the 4 weeks before Screening
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
GI disorder (e.g., severe erosive esophagitis, Zollinger Ellison syndrome) or surgery leading to impaired drug absorption
Peptic ulcer disease within 6 months prior to Screening
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
Schizophrenia or bipolar disorder
Subjects who had started physical therapy on the index joint less than 6 weeks prior to study Screening
Use of any excluded concomitant medication
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
Serious blood coagulation disorder including use of systemic anti-coagulants
Screening laboratory value for alanine aminotransferase, aspartate aminotransferase greater than 2 times the upper limit of normal
Estimated creatinine clearance less than 30 ml/min
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
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
Previous participation in another PN 400 clinical research trial
Subjects who were employees of the research facility or who were in some way under the supervision of the principal investigator for this study

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00665431

Locations

United States, North Carolina
POZEN
Chapel Hill, North Carolina, United States, 27517

Sponsors and Collaborators

POZEN

Investigators

Study Chair:

Everardus Orlemans, PhD

POZEN

More Information

No publications provided by POZEN

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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. Epub 2011 Apr 28.

Responsible Party:	Pozen
ClinicalTrials.gov Identifier:	NCT00665431 History of Changes
Other Study ID Numbers:	PN400-309
Study First Received:	April 18, 2008
Results First Received:	May 27, 2010
Last Updated:	November 1, 2011
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Osteoarthritis
Osteoarthritis, Knee
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Antacids
Anti-Ulcer Agents
Celecoxib
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Gastrointestinal Agents
Therapeutic Uses

Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Central Nervous System Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on May 16, 2013