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

This study has been terminated.
(POZEN agreed with FDA to stop study due to low and inadequate enrollment)
Sponsor:
Information provided by:
POZEN
ClinicalTrials.gov Identifier:
NCT00594854
First received: December 19, 2007
Last updated: August 27, 2010
Last verified: August 2010
  Purpose

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.


Condition Intervention Phase
Gastric Ulcer
Drug: PN400 (VIMOVO)
Drug: Diclofenac/Misoprostol
Phase 3

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

Resource links provided by NLM:


Further study details as provided by POZEN:

Primary Outcome Measures:
  • Number of Participants With Gastric Ulcer Confirmed by Endoscopy [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Number of Participants With Duodenal Ulcers Confirmed by Endoscopy [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Number of participants with duodenal ulcers confirmed by endoscopy following administration of PN 400 VIMOVO)or Arthrotec in a high risk population

  • Number of Participants With Upper Gastro-intestinal Injury Grade 4 as Measured by Lanza (1991) Score [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 20
Study Start Date: September 2007
Study Completion Date: September 2008
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PN400
PN 400 (esomeprazole/naproxen) dosed twice daily
Drug: PN400 (VIMOVO)
PN400 tablet (500 mg delayed-release naproxen/20 mg immediate-release esomeprazole) given by mouth twice daily (bid).
Other Name: Vimovo
Active Comparator: Diclofenac/Misoprostol
diclofenac 75mg/misoprostol 200 mcg dosed twice daily
Drug: Diclofenac/Misoprostol
Over-encapsulated ARTHROTEC® 75 (75 mg diclofenac sodium/200 mcg misoprostol) capsules given by mouth bid.
Other Name: Arthrotec

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 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
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00594854

Locations
United States, North Carolina
POZEN
Chapel Hill, North Carolina, United States, 27517
Sponsors and Collaborators
POZEN
Investigators
Study Chair: Everardus Orlemans, PhD POZEN
  More Information

No publications provided

Responsible Party: Everardus Orlemans, PhD, VP, Clinical Research, POZEN Inc
ClinicalTrials.gov Identifier: NCT00594854     History of Changes
Other Study ID Numbers: PN400-303
Study First Received: December 19, 2007
Results First Received: May 28, 2010
Last Updated: August 27, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by POZEN:
NSAID
Gastric Ulcer
High risk
Arthrotec
Vimovo

Additional relevant MeSH terms:
Stomach Ulcer
Ulcer
Peptic Ulcer
Gastrointestinal Diseases
Digestive System Diseases
Stomach Diseases
Pathologic Processes
Naproxen
Diclofenac
Arthrotec
Esomeprazole
Misoprostol
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Gout Suppressants
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Central Nervous System Agents
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents

ClinicalTrials.gov processed this record on August 20, 2014