Evaluating PN 400 (VIMOVO) in Reducing Gastric Ulcers Compared to Non-steroidal Antiinflammatory Drug (NSAID) Naproxen

Official Title: “6-Month, Phase 3, Randomized, Double-blind, Parallel-group, Controlled, Multi-center Study Evaluate Gastric Ulcer Incidence Following Administration of PN400 or Naproxen in Subjects Who Are at Risk for Developing NSAID-associated Ulcers”

This study uses a randomized, double-blind, controlled design to demonstrate that PN400 (esomeprazole and naproxen) is more effective in reducing the occurrence of gastroduodenal ulcers, dyspepsia, and heartburn in subjects at risk for developing NSAID-associated gastric ulcers compared to naproxen alone.

Objectives:

Primary: To demonstrate that PN400 is effective in reducing the risk of gastric ulcers in subjects at risk for developing NSAID-associated gastric ulcers.

Secondary: - To determine if PN400 is effective in reducing the risk of duodenal ulcers in subjects at risk for developing NSAID-associated ulcers - To compare upper gastrointestinal symptoms in subjects treated with PN400 versus naproxen as measured by scores on the Severity of Dyspepsia Assessment (SODA) instrument and the Overall Treatment Evaluation - Dyspepsia (OTE-DP) - To compare heartburn symptoms in subjects treated with PN400 versus naproxen - To evaluate the safety and tolerability of PN400 and naproxen

Intervention(s) in this Clinical Trial

• Drug: PN400 (VIMOVO)
  • PN400 tablets (Naproxen 500 mg and Esomeprazole 20 mg) twice daily (bid) taken orally.
• Drug: Naproxen
  • Naproxen (500 mg) dosed twice daily (bid) orally

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: PN400
  • Naproxen 500 mg/Immediate-Release Esomeprazole 20 mg dosed twice daily
• Active Comparator: Naproxen
  • Naproxen 500 mg dosed twice daily

Primary Measures

• Number of Participants With Gastric Ulcer Confirmed by Endoscopy
  • Time Frame: 6 months
    Safety Issue?: Yes

Secondary Measures

• The Number of Participants With Pre-Specified NSAID-Associated Upper GI Adverse Events or Duodenal Ulcers
  • Time Frame: 6 months
    Safety Issue?: Yes
• The Number of Participants Discontinuing From the Study Due to NSAID-Associated Upper GI Adverse Events or to Duodenal Ulcer
  • Time Frame: 6 Months
    Safety Issue?: Yes
• The Number of Participants Developing Duodenal Ulcers Throughout 6 Months of Treatment
  • Time Frame: 6 months
    Safety Issue?: Yes
• Heartburn Symptom Resolution, ie no Heartburn Symptoms During the Last 7 Days Prior to the Visit
  • Time Frame: 6 months
    Safety Issue?: Yes
• Improvement From Baseline in Upper Abdominal Pain and Discomfort Scores at 6 Months, Based on the Overall Treatment Evaluation for Dyspepsia Questionnaire
  • Time Frame: change from baseline at 6 Months
    Safety Issue?: Yes
• Mean Change From Baseline on Pain Intensity of the Severity of Dyspepsia Assessment (SODA) Subscales
  • Time Frame: baseline to 6 Months
    Safety Issue?: Yes
• Mean Change From Baseline on Non-Pain Symptoms of the Severity of Dyspepsia Assessment (SODA) Subscales
  • Time Frame: baseline to 6 Months
    Safety Issue?: Yes
• Mean Change From Baseline on Satisfaction of the Severity of Dyspepsia Assessment (SODA) Subscales
  • Time Frame: baseline to 6 Months
    Safety Issue?: Yes

Inclusion Criteria

• A subject was eligible for inclusion in this study if all of the following criteria applied:
• 1. Male or non-pregnant, non-breastfeeding female subjects with a history of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis or other medical conditions expected to require daily NSAID therapy for at least 6 months, who were
• 18-49 years of age and had a history of a documented, uncomplicated gastric or duodenal ulcer (a mucosal break of at least 3 mm in diameter with depth, without any concurrent bleeding, clot or perforation) within the past 5 years OR, who were
• 50 years of age and older (These subjects did not require a history of a documented, uncomplicated gastric or duodenal ulcer within the past 5 years.)
• 2. Female subjects were eligible for participation in the study if they were of
• non-childbearing potential (i.e., physiologically incapable of becoming pregnant);
• childbearing potential, had a negative pregnancy test at Screening, and at least 1 of the following applied or was agreed to by the subject:
• Female sterilization or sterilization of male partner
• Hormonal contraception by oral route, implant, injectable, vaginal ring
• Any intrauterine device with published data showing that the lowest expected failure rate is < 1% per year
• Double barrier method (2 physical barriers or 1 physical barrier plus spermicide)
• Any other method with published data showing that the lowest expected failure rate is < 1% per year
• 3. Each subject was required to understand and comply with study procedures required of a subject and was able and willing to provide written informed consent prior to any study procedures being performed.

Exclusion Criteria

• A subject was not eligible for this study if any 1 or more of the following criteria applied:
• 1. History of hypersensitivity to esomeprazole or to another PPI
• 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. Participation in any study of an investigational treatment in the 4 weeks before
• Screening
• 4. Presence of uncontrolled acute or chronic medical illness, e.g., GI disorder, hypertension, diabetes, thyroid disorder, depression and/or infection that would have endangered a subject if they were to have participated in the study
• 5. GI disorder or surgery leading to impaired drug absorption
• 6. Evidence of uncontrolled, or unstable cardio- or cerebrovascular disorder, which in the investigator's opinion would have endangered a subject if they were to have participated in the study
• 7. Schizophrenia or bipolar disorder
• 8. Use of any excluded concomitant medication (see Section 9.4.8)
• 9. 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
• 10. Serious blood coagulation disorder, including use of systemic anticoagulants
• 11. Positive test result for H. pylori at Screening
• 12. Screening endoscopy showing any gastric or duodenal ulcer at least 3 mm in diameter with depth
• 13. Screening laboratory alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value > 2 times the upper limit of normal
• 14. Estimated creatinine clearance < 30 ml/min
• 15. Other than noted specifically, any screening laboratory value that was clinically significant in the investigator's opinion and would have endangered a subject if they were to have participated 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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: POZEN Industry

Overall Clinical Trial Officials and Contacts

Everardus Orlemans, PhD Study Chair POZEN  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00527787

Study ID Number: PN400-301

ClinicalTrials.gov Identifier: NCT00527787

Health Authority: United States: Food and Drug Administration