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

NCT ID: NCT00594854

Last Updated: 2010-09-22

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-09-30
• Study Completion Date: 2008-09-30

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

Conditions

Gastric Ulcer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

PN400

PN 400 (esomeprazole/naproxen) dosed twice daily

Group Type: EXPERIMENTAL

PN400 (VIMOVO)

Intervention Type: DRUG

PN400 tablet (500 mg delayed-release naproxen/20 mg immediate-release esomeprazole) given by mouth twice daily (bid).

Diclofenac/Misoprostol

diclofenac 75mg/misoprostol 200 mcg dosed twice daily

Group Type: ACTIVE_COMPARATOR

Diclofenac/Misoprostol

Intervention Type: DRUG

Over-encapsulated ARTHROTEC® 75 (75 mg diclofenac sodium/200 mcg misoprostol) capsules given by mouth bid.

Interventions

PN400 (VIMOVO)

PN400 tablet (500 mg delayed-release naproxen/20 mg immediate-release esomeprazole) given by mouth twice daily (bid).

Intervention Type: DRUG

Diclofenac/Misoprostol

Over-encapsulated ARTHROTEC® 75 (75 mg diclofenac sodium/200 mcg misoprostol) capsules given by mouth bid.

Intervention Type: DRUG

Other Intervention Names

Vimovo; Arthrotec

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

POZEN

INDUSTRY

Sponsor Role: lead

Responsible Party

POZEN Inc

Principal Investigators

Everardus Orlemans, PhD

Role: STUDY_CHAIR

POZEN

Locations

POZEN

Chapel Hill, North Carolina, United States

Countries

United States

Other Identifiers

PN400-303

Identifier Type: -

Identifier Source: org_study_id