Evaluating PN 400 (VIMOVO) in Reducing Gastric Ulcers in High Risk Subjects Compared to Arthrotec

Official Title: “6-Month, Randomized, Double-blind, Parallel-group, Controlled, Multi-center Study of Gastric Ulcer Incidence With PN400 (Esomeprazole/Naproxen) Versus Diclofenac/Misoprostol in Subjects at High Risk for Developing NSAID-Associated Ulcers”

This randomized, double-blind, parallel-group, controlled, multi-center clinical trial of 6 months duration is designed to assess the efficacy, tolerability and safety of PN400 versus diclofenac/misoprostol in subjects at high risk for developing NSAID-associated gastric ulcers. Approximately 100 sites will participate to enroll a total of 200 subjects (100 per arm).

At least 20% of the subjects enrolled will be age 65 years and older.

To determine the incidence of gastric ulcers following administration of PN 400 in a high risk population over six months. Diclofenac/misoprostol will be used as a positive control.

Secondary: - To determine the incidence of duodenal ulcers during treatment with PN 400 and diclofenac/misoprostol in a high risk population - To evaluate the degree of upper gastrointestinal injury as measured by Lanza scores (1991) during treatment with PN400 and diclofenac/misoprostol in a high risk population - To compare gastrointestinal symptoms in subjects treated with PN 400 versus diclofenac/misoprostol as measured by scores on the Gastrointestinal Symptoms Rating Scale (GSRS) instrument - To evaluate the safety and tolerability of PN400 and diclofenac/misoprostol in a high risk population

Intervention(s) in this Clinical Trial

• Drug: PN400 (VIMOVO)
  • PN400 tablet (500 mg delayed-release naproxen/20 mg immediate-release esomeprazole) given by mouth twice daily (bid).
• Drug: Diclofenac/Misoprostol
  • Over-encapsulated ARTHROTEC® 75 (75 mg diclofenac sodium/200 mcg misoprostol) capsules given by mouth bid.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: PN400
  • PN 400 (esomeprazole/naproxen) dosed twice daily
• Active Comparator: Diclofenac/Misoprostol
  • diclofenac 75mg/misoprostol 200 mcg dosed twice daily

Primary Measures

• Number of Participants With Gastric Ulcer Confirmed by Endoscopy
  • Time Frame: 6 months
    Safety Issue?: Yes

Secondary Measures

• Number of Participants With Duodenal Ulcers Confirmed by Endoscopy
  • Time Frame: 6 months
    Safety Issue?: Yes
• Number of Participants With Upper Gastro-intestinal Injury Grade 4 as Measured by Lanza (1991) Score
  • Time Frame: 6 months
    Safety Issue?: Yes

Inclusion Criteria:

• 1. Male or non-pregnant female subjects, 18 years and older with a history of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis or other medical condition expected to require daily NSAID therapy for at least 6 months, with a documented history of an ulcer related serious upper gastrointestinal event such as bleeding, perforation or obstruction
• 2. Female subjects are eligible for participation in the study if they are of:
• Non-childbearing potential (i.e., physiologically incapable of becoming pregnant);
• Childbearing potential, have a negative pregnancy test at screening, and at least one of the following applies or is agreed to by the subject:
• Female sterilization or sterilization of male partner; or,
• Hormonal contraception by oral route, implant, injectable, vaginal ring;
• or,
• Any intrauterine device (IUD) with published data showing that the lowest expected failure rate is less than 1% per year;
• Double barrier method (2 physical barriers or 1 physical barrier plus spermicide); or
• Any other method with published data showing that the lowest expected failure rate is less than 1% per year
• 3. Each subject must be able to understand and comply with study procedures required of a subject and is able and willing to provide written informed consent prior to any study procedures being performed

Exclusion Criteria:

• 1. History of hypersensitivity to esomeprazole or to another proton-pump inhibitor
• 2. History of allergic reaction or intolerance to any NSAID (including aspirin) and/or a history of NSAID-induced symptoms of asthma, rhinitis, and/or nasal polyps
• 3. Positive test result for H. pylori at screening
• 4. Participation in any study of an investigational treatment in the 4 weeks before screening
• 5. Presence of uncontrolled acute or chronic medical illness, e.g. gastrointestinal disorder, hypertension, diabetes, thyroid disorder, depression and/or infection that would endanger a subject if they were to participate in the study
• 6. Gastrointestinal disorder or surgery leading to impaired drug absorption
• 7. Evidence of uncontrolled, or unstable cardio- or cerebrovascular disorder, which in the investigator's opinion would endanger a subject if they were to participate in the study
• 8. Schizophrenia or bipolar disorder
• 9. Use of any excluded concomitant medication (see Section 9.2)
• 10. 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
• 11. Serious blood coagulation disorder, including use of systemic anticoagulants
• 12. Screening endoscopy showing >10 erosions or any gastric or duodenal ulcer at least 3 mm in diameter with depth
• 13. Screening laboratory ALT or AST value > 2 times the upper limit of normal
• 14. Estimated creatinine clearance < 50 ml/min
• 15. Other than noted specifically, any screening laboratory value that is clinically significant in the investigator's opinion and would endanger a subject if they were to participate in the study
• 16. 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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: POZEN Industry

Overall Clinical Trial Officials and Contacts

Everardus Orlemans, PhD Study Chair POZEN  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00594854

Study ID Number: PN400-303

ClinicalTrials.gov Identifier: NCT00594854

Health Authority: United States: Food and Drug Administration