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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
POZEN
ClinicalTrials.gov Identifier:
NCT00664560
First received: April 18, 2008
Last updated: January 20, 2012
Last verified: January 2012
  Purpose

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


Condition Intervention Phase
Osteoarthritis
Drug: PN 400 (VIMOVO)
Drug: celebrex
Drug: 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:


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:
  • American Pain Society Patient Outcome Questionnaire (APS-POQ)Total Interference Caused by Pain. [ Time Frame: Baseline and Day 7 ] [ Designated as safety issue: No ]
    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.

  • 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: Baseline to 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: 614
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
Drug: PN 400 (VIMOVO)
500 mg naproxen/20 mg esomeprazole bid
Other Name: PN 400
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
Drug: 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

  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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00664560

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):
Responsible Party: POZEN
ClinicalTrials.gov Identifier: NCT00664560     History of Changes
Other Study ID Numbers: PN400-307
Study First Received: April 18, 2008
Results First Received: May 27, 2010
Last Updated: January 20, 2012
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 July 23, 2014