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

Study Overview
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Brief Summary
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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.

Detailed Description
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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

Official Title
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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

Conditions
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Gastric Ulcer

Intervention / Treatment
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* Drug: PN400 (VIMOVO)
* Drug: Diclofenac/Misoprostol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 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 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: History of hypersensitivity to esomeprazole or to another proton-pump inhibitor 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 Positive test result for H. pylori at screening Participation in any study of an investigational treatment in the 4 weeks before screening 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 Gastrointestinal disorder or surgery leading to impaired drug absorption 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 Schizophrenia or bipolar disorder Use of any excluded concomitant medication (see Section 9.2) 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 Screening endoscopy showing >10 erosions or any gastric or duodenal ulcer at least 3 mm in diameter with depth Screening laboratory ALT or AST value > 2 times the upper limit of normal Estimated creatinine clearance < 50 ml/min 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 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PN400<br>PN 400 (esomeprazole/naproxen) dosed twice daily | Drug: PN400 (VIMOVO)<br>* PN400 tablet (500 mg delayed-release naproxen/20 mg immediate-release esomeprazole) given by mouth twice daily (bid).<br>* Other names: Vimovo;|
| Active Comparator: Diclofenac/Misoprostol<br>diclofenac 75mg/misoprostol 200 mcg dosed twice daily | Drug: Diclofenac/Misoprostol<br>* Over-encapsulated ARTHROTEC® 75 (75 mg diclofenac sodium/200 mcg misoprostol) capsules given by mouth bid.<br>* Other names: Arthrotec;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Gastric Ulcer Confirmed by Endoscopy | Number of participants with gastric ulcers confirmed by endoscopy following administration of PN 400 (VIMOVO) or Arthrotec in a high risk population over six months. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Duodenal Ulcers Confirmed by Endoscopy | Number of participants with duodenal ulcers confirmed by endoscopy following administration of PN 400 VIMOVO)or Arthrotec in a high risk population | 6 months | 
| Number of Participants With Upper Gastro-intestinal Injury Grade 4 as Measured by Lanza (1991) Score | The degree of upper gastrointestinal (UGI) injury as measured by Lanza scores (1991) during treatment with PN 400 and ARTHROTEC® in a high-risk population. The Lanza (1991) score is based on endoscopic obeservations and rating these, with no damage, petecchiae, erosions and ulcers. On the 1991 scale, a Lanza score of 0 represents normal mucosa (no damage), while a score of 4 indicates 6-10 erosions, and a score of 7 indicates an ulcer. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NSAID, Gastric Ulcer, High risk, Arthrotec, Vimovo