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

Gastric Ulcer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00594854
• Other study ID #: PN400-303
• Status: Terminated
• Phase: Phase 3
• First received: December 19, 2007
• Last updated: August 27, 2010
• Start date: September 2007
• Est. completion date: September 2008

Study information

• Verified date: August 2010
• Source: POZEN
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 20
• Est. completion date: September 2008
• Est. primary completion date: September 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Gastric Ulcer
• Stomach Ulcer
• Ulcer

Intervention

Drug:
• PN400 (VIMOVO)
PN400 tablet (500 mg delayed-release naproxen/20 mg immediate-release esomeprazole) given by mouth twice daily (bid).
• Diclofenac/Misoprostol
Over-encapsulated ARTHROTEC® 75 (75 mg diclofenac sodium/200 mcg misoprostol) capsules given by mouth bid.

Locations

Country	Name	City	State
United States	POZEN	Chapel Hill	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
POZEN

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	Yes
Secondary	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	Yes