Official Title: “A 6-Month, Randomized, Double-Blind, Parallel-Group, Controlled, Multi-Center Study to Evaluate the Incidence of Gastric Ulcers With PN 400 (Esomeprazole/Naproxen) Versus Diclofenac/Misoprostol in Subjects Who Are 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 PN 400 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.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Active Control, Parallel Assignment, Safety/Efficacy Study

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 PN 400 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 PN 400 and diclofenac/misoprostol in a high risk population

Primary:

• 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 6 months Yes

Secondary:

• To determine the incidence of duodenal ulcers during treatment with PN 400 and diclofenac/misoprostol in a high risk population 6 months 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

Lead Sponsor: Pozen

Patient Interaction - Call Center

Chapel Hill North Carolina 27517 United States

Overall Clinical Trial Officials and Contacts

Patient Interaction Call Center Study Chair Patient Interaction  

Information obtained from ClinicalTrials.gov on July 23, 2008

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