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

NCT00527787 | Completed Phase 3 Results DMC

• 1 other identifier: PN400-301
• Study Type: interventional
• Target: 434
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Gastric Ulcer

Keywords

NSAID; gastric ulcers; Vimovo; Naproxen; Esomeprazole

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Gastric Ulcer Confirmed by Endoscopy

  The primary efficacy endpoint was the number of subjects with gastric ulcers at any time throughout 6 months of treatment. An ulcer was defined as a mucosal break of at least 3 mm in diameter (measured by close application of open endoscopic biopsy forceps) with unequivocal crater depth. A subject is considered to have completed the study if all scheduled assessments up through the 6 month visit have been performed or if the endpoint of gastric ulcer confirmed by endoscopy has been reached.

  6 months

Secondary Outcomes (8)

• The Number of Participants With Pre-Specified NSAID-Associated Upper GI Adverse Events or Duodenal Ulcers

  6 months

• The Number of Participants Discontinuing From the Study Due to NSAID-Associated Upper GI Adverse Events or to Duodenal Ulcer

  6 Months

• The Number of Participants Developing Duodenal Ulcers Throughout 6 Months of Treatment

  6 months

• Heartburn Symptom Resolution, ie no Heartburn Symptoms During the Last 7 Days Prior to the Visit

  6 months

• Improvement From Baseline in Upper Abdominal Pain and Discomfort Scores at 6 Months, Based on the Overall Treatment Evaluation for Dyspepsia Questionnaire

  change from baseline at 6 Months

Study Arms (2)

PN400

EXPERIMENTAL

Naproxen 500 mg/Immediate-Release Esomeprazole 20 mg dosed twice daily

Drug: PN400 (VIMOVO)

Naproxen

ACTIVE COMPARATOR

Naproxen 500 mg dosed twice daily

Drug: Naproxen

Interventions

PN400 (VIMOVO) DRUG

PN400 tablets (Naproxen 500 mg and Esomeprazole 20 mg) twice daily (bid) taken orally.

Also known as: Vimovo

PN400

Naproxen DRUG

Naproxen (500 mg) dosed twice daily (bid) orally

Also known as: Naprosyn

Naproxen

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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
• 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.)
• 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
• 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.

You may not qualify if:

• A subject was not eligible for this study if any 1 or more of the following criteria applied:
• History of hypersensitivity to esomeprazole or to another PPI
• 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
• Participation in any study of an investigational treatment in the 4 weeks before Screening
• 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
• GI disorder or surgery leading to impaired drug absorption
• 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
• Schizophrenia or bipolar disorder
• Use of any excluded concomitant medication (see Section 9.4.8)
• 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
• Serious blood coagulation disorder, including use of systemic anticoagulants
• Positive test result for H. pylori at Screening
• Screening endoscopy showing any gastric or duodenal ulcer at least 3 mm in diameter with depth
• Screening laboratory alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value \> 2 times the upper limit of normal
• Estimated creatinine clearance \< 30 ml/min

Sponsors & Collaborators

• POZEN: lead

Study Sites (1)

POZEN

Chapel Hill, North Carolina, 27517, United States

Location

MeSH Terms

Conditions

Stomach Ulcer

Interventions

Naproxen

Condition Hierarchy (Ancestors)

Peptic Ulcer; Duodenal Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Naphthaleneacetic Acids; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Results Point of Contact

• Title: Senior Vice President, Clinical Research
• Organization: POZEN Inc

eorlemans@pozen.com

919-913-1030

Study Officials

• Everardus Orlemans, PhD

  POZEN

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: September 10, 2007
• First Posted: September 11, 2007
• Study Start: September 1, 2007
• Primary Completion: October 1, 2008
• Study Completion: October 1, 2008
• Last Updated: December 28, 2010
• Results First Posted: December 28, 2010

Record last verified: 2010-11

Locations

US (1)