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

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

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.

Study Overview

• Status: Terminated
• Conditions: Gastric Ulcer
• Intervention / Treatment: Drug: PN400 (VIMOVO); Drug: Diclofenac/Misoprostol

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

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27517
      • Pozen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: POZEN

Study record dates

Study Major Dates

• Study Start: September 1, 2007
• Primary Completion (ACTUAL): September 1, 2008
• Study Completion (ACTUAL): September 1, 2008

Study Registration Dates

• First Submitted: December 19, 2007
• First Submitted That Met QC Criteria: January 15, 2008
• First Posted (ESTIMATE): January 16, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): September 22, 2010
• Last Update Submitted That Met QC Criteria: August 27, 2010
• Last Verified: August 1, 2010

More Information

Terms related to this study

• Keywords: NSAID; High risk; Vimovo; Gastric Ulcer; Arthrotec
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Stomach Diseases; Intestinal Diseases; Peptic Ulcer; Duodenal Diseases; Ulcer; Stomach Ulcer; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Gastrointestinal Agents; Reproductive Control Agents; Anti-Ulcer Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Oxytocics; Misoprostol; Diclofenac; Arthrotec
• Other Study ID Numbers: PN400-303