Official Title: “A Multicenter, Open-Label, Four-Way Crossover Study of the Effects of Esomeprazole, Aspirin and Rofecoxib on Prostaglandin (PGE2) Production, Cyclooxygenase-2 Enzyme Activity and PCNA Expression in Patients With Barrett's Esophagus”

This study evaluates PGE2 production, COX-2 enzyme activity and PCNA expression in Barrett's metaplastic tissue. All patients will have a baseline endoscopy with multiple biopsies. The patients will then be receive four dosing regimens (esomeprazole, esomeprazole and aspirin, esomeprazole and rofecoxib, or rofecoxib alone) consecutively each for a 10 day dosing period, whilst undergoing further follow up endoscopies and multiple biopsies.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Crossover Assignment, Efficacy Study

Primary:

• Measure PGE production in Barrett's metastatic tissue & determine the reduction from baseline of PGE production would be equivalent on Day 10 in esomeprazole 40mg bid + aspirin treatment compared to esomeprazole 40 mg bid + rofecoxib 25 mg qd treatment Baseline esophageal biopsies will be taken and thereafter at Day 10 in each treatment period.

Secondary:

• To determine in which of the four treatment groups the reduction in the baseline in PGE2 production, COX-2 enzyme activity and PCNA expression in Barrett's metaplastic tissue is the greatest. Baseline esophageal biopsies will be taken and thereafter at Day 10 in each treatment period

Inclusion Criteria:

• A biopsy-proven diagnosis of Barrett's esophagus segment length greater than 2cm with no dysplasia or adenocarcinoma.
• Clinically normal laboratory results and physical findings at screening.

Exclusion Criteria:

• A history of esophageal, gastric or duodenal surgery, including antireflux surgery or endoscopic antireflux procedures, except for simple closure of an ulcer.
• Evidence of the following diseases or conditions:
• Barrett's esophagus less than or greater than 2cm that is positive for high grade dysplasia or adenocarcinoma
• Signs and symptoms of gastric outlet obstruction
• Active peptic ulcer disease
• severe liver disease
• Pancreatitis
• Malabsorption
• Active inflammatory bowel disease
• Severe pulmonary, cardiovascular or renal disease
• Impaired renal function or abnormal urine sediment on repeated examinations
• esophageal stricture or active, severe esophagitis.

Lead Sponsor: AstraZeneca

Overall Clinical Trial Officials and Contacts

Paula Fernstrom Study Director Nexium Global Product Director, AstraZeneca  

Information obtained from ClinicalTrials.gov on July 23, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00637988

Study ID Number: 316

ClinicalTrials.gov Identifier: NCT00637988

Health Authority: United States: Food and Drug Administration