A 12-month, Phase 3, Open-label, Multi-center Study to Evaluate the Long-term Safety of PN400 (VIMOVO)

Study Overview
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Brief Summary
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This study uses an open-label design and will be conducted in approximately 60 sites aiming to enroll a total number of 200 subjects to ensure that at least 100 subjects will have 12 months exposure to PN400 (VIMOVO).

Detailed Description
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PN400 is proposed for the treatment of the signs and symptoms of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis or other medical conditions expected to require daily NSAID therapy for at least 12 months in patients at risk for developing NSAID-associated gastric ulcers. This study is designed to provide long-term safety data for PN400 in order to gain regulatory approval to make PN400 available for clinical use in this subject population.

Official Title
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A 12-month, Phase 3, Open-label, Multi-center Study to Evaluate the Long-term Safety of PN400 in Subjects Who Are at Risk for Developing NSAID-associated Ulcers

Conditions
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Gastric Ulcer

Intervention / Treatment
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* Drug: PN400 (VIMOVO)
* Drug: PN 400 (VIMOVO)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria A subject was eligible for inclusion in this study if all of the following criteria applied: Male or non-pregnant female subjects with a history of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis or other medical conditions expected to require daily NSAID therapy for at least 12 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 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; or, Hormonal contraception by oral route, implant, injectable, vaginal ring; or, Any intrauterine device with published data showing that the lowest expected failure rate is less than 1% per year; or, 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 was required to be able and willing to provide written informed consent prior to any study procedures being performed. Exclusion Criteria A subject was not eligible for inclusion in 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 he/she were to participate 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 he/she were to participate in the study Schizophrenia or bipolar disorder Use of any excluded concomitant medication 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 Helicobacter pylori at Screening Baseline endoscopy showing any gastric or duodenal ulcer at least 3 mm in diameter with depth Screening laboratory value for any of the following tests that was > 2 times the upper limit of normal: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) Estimated creatinine clearance < 50 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 the subject 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PN 400 (VIMOVO)<br>500 mg delayed release naproxen/20 mg immediate release esomeprazole | Drug: PN400 (VIMOVO)<br>* Subjects are instructed to take 2 tablets a day, one in the morning and one in the afternoon/evening. The morning tablet should be taken with water, on an empty stomach 30 to 60 minutes before breakfast, or the first meal. The afternoon/evening tablet should be taken with water, on an empty stomach 30 to 60 minutes before dinner. Tablets should be swallowed whole and not broken, crushed or chewed.<br>* Other names: Nexium;Drug: PN 400 (VIMOVO)<br>* 500 mg delayed-release naproxen/20 mg immediate release esomperazole dosed twice daily for 12 months<br>* Other names: Nexium;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Monitored for Long-term Safety of PN 400 | Incidence of adverse events and monitoring vital signs, clinical laboratory values, physical exams, ECG. All AEs were coded into preferred terms according to MedDRA (Medical Dictionary for Regulatory Activities) and classified by system organ class (SOC). Summaries of the incidence of all treatment-emergent AEs, treatment-related AEs, SAEs, and AEs leading to study drug discontinuation were prepared. Treatment-emergent AEs were also summarized by maximum severity, by quartile of number of doses taken and by treatment window. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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osteoarthritis, rheumatoid arthritis, ankylosing spondylisit, NSAIDS