evaluating pn 400 (vimovo) in reducing gastric ulcers in high risk subjects compared to arthrotec

Conditions: Gastric Ulcer

Summary: 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

Eligibility criteria:
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

Keywords: nsaid gastric ulcer high risk arthrotec vimovo