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

Phase 3

Terminated

Conditions: Gastric Ulcer

Interventions: Drug: PN400 (VIMOVO)
Drug: Diclofenac/Misoprostol

Registration Number: NCT00594854

Lead Sponsor: POZEN

Brief 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.

Detailed Description: 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

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 20

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PN400	PN400 (VIMOVO)	PN 400 (esomeprazole/naproxen) dosed twice daily
Diclofenac/Misoprostol	Diclofenac/Misoprostol	diclofenac 75mg/misoprostol 200 mcg dosed twice daily

Primary Outcome Measures

Name	Time	Method
Number of Participants With Gastric Ulcer Confirmed by Endoscopy	6 months	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.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Duodenal Ulcers Confirmed by Endoscopy	6 months	Number of participants with duodenal ulcers confirmed by endoscopy following administration of PN 400 VIMOVO)or Arthrotec in a high risk population
Number of Participants With Upper Gastro-intestinal Injury Grade 4 as Measured by Lanza (1991) Score	6 months	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.