Study to Evaluate the Incidence of Gastric Ulcers With PN 400 (Esomeprazole/Naproxen) Versus Diclofenac/Misoprostol in Subjects Who Are at High Risk for Developing NSAID-Associated Ulcers

Condition(s) targeted: Gastric Ulcer

Intervention: Diclofenac/misoprostol (Drug); PN400 (Drug)

Phase: Phase 3

Status: Terminated

Sponsored by: Pozen

Official(s) and/or principal investigator(s):
Patient Interaction Call Center, Study Chair, Affiliation: Patient Interaction

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 PN 400 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.

Official title: A 6-Month, Randomized, Double-Blind, Parallel-Group, Controlled, Multi-Center Study to Evaluate the Incidence of Gastric Ulcers With PN 400 (Esomeprazole/Naproxen) Versus Diclofenac/Misoprostol in Subjects Who Are at High Risk for Developing NSAID-Associated Ulcers

Study design: Treatment, Randomized, Double Blind (Subject, Investigator), Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: 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 outcome: To determine the incidence of duodenal ulcers during treatment with PN 400 and diclofenac/misoprostol in a high risk population

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 PN 400 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 PN 400 and diclofenac/misoprostol in a high

risk population

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

Patient Interaction - Call Center, Chapel Hill, North Carolina 27517, United States

Starting date: September 2007
Ending date: September 2008
Last updated: May 27, 2008