Evaluating PN 400 (VIMOVO) in Reducing Gastric Ulcers Compared to Non-steroidal Antiinflammatory Drug (NSAID) Naproxen

Objectives:

Primary: To demonstrate that PN400 is effective in reducing the risk of gastric ulcers in subjects at risk for developing NSAID-associated gastric ulcers.

Secondary:

• To determine if PN400 is effective in reducing the risk of duodenal ulcers in subjects at risk for developing NSAID-associated ulcers
• To compare upper gastrointestinal symptoms in subjects treated with PN400 versus naproxen as measured by scores on the Severity of Dyspepsia Assessment (SODA) instrument and the Overall Treatment Evaluation - Dyspepsia (OTE-DP)
• To compare heartburn symptoms in subjects treated with PN400 versus naproxen
• To evaluate the safety and tolerability of PN400 and naproxen

Inclusion criteria

A subject was eligible for inclusion in this study if all of the following criteria applied:

• Male or non-pregnant, non-breastfeeding female subjects with a history of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis or other medical conditions expected to require daily NSAID therapy for at least 6 months, who were

• 18-49 years of age and had a history of a documented, uncomplicated gastric or duodenal ulcer (a mucosal break of at least 3 mm in diameter with depth, without any concurrent bleeding, clot or perforation) within the past 5 years OR, who were
• 50 years of age and older (These subjects did not require a history of a documented, uncomplicated gastric or duodenal ulcer within the past 5 years.)
• Female subjects were eligible for participation in the study if they were of

• non-childbearing potential (i.e., physiologically incapable of becoming pregnant);
• childbearing potential, had a negative pregnancy test at Screening, and at least 1 of the following applied or was agreed to by the subject:
• Female sterilization or sterilization of male partner
• Hormonal contraception by oral route, implant, injectable, vaginal ring
• Any intrauterine device with published data showing that the lowest expected failure rate is < 1% per year
• Double barrier method (2 physical barriers or 1 physical barrier plus spermicide)
• Any other method with published data showing that the lowest expected failure rate is < 1% per year
• Each subject was required 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.

Exclusion criteria

A subject was not eligible for this study if any 1 or more of the following criteria applied:

• History of hypersensitivity to esomeprazole or to another PPI
• 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
• Participation in any study of an investigational treatment in the 4 weeks before Screening
• Presence of uncontrolled acute or chronic medical illness, e.g., GI disorder, hypertension, diabetes, thyroid disorder, depression and/or infection that would have endangered a subject if they were to have participated in the study
• GI disorder or surgery leading to impaired drug absorption
• Evidence of uncontrolled, or unstable cardio- or cerebrovascular disorder, which in the investigator's opinion would have endangered a subject if they were to have participated in the study
• Schizophrenia or bipolar disorder
• Use of any excluded concomitant medication (see Section 9.4.8)
• 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 anticoagulants
• Positive test result for H. pylori at Screening
• Screening endoscopy showing any gastric or duodenal ulcer at least 3 mm in diameter with depth
• Screening laboratory alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value > 2 times the upper limit of normal
• Estimated creatinine clearance < 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 they were to have participated 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