Evaluating PN 400 (VIMOVO) in Reducing Gastric Ulcers Compared to Non-steroidal Antiinflammatory Drug (NSAID) Naproxen
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.
|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, 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|
- Number of Participants With Gastric Ulcer Confirmed by Endoscopy [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]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.
- The Number of Participants With Pre-Specified NSAID-Associated Upper GI Adverse Events or Duodenal Ulcers [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]The Number of Participants with Pre-Specified non-steroidal antiinflammatory drug (NSAID)-Associated Upper Gastrointestinal (UGI) Adverse Events or Duodenal Ulcers after 6 months of treatment. Pre-specified UGI adverse events typically associated with NSAID use include dyspepsia, abdominal pain, gastritis, erosive esophagitis, duodenitis, abdominal discomfort
- The Number of Participants Discontinuing From the Study Due to NSAID-Associated Upper GI Adverse Events or to Duodenal Ulcer [ Time Frame: 6 Months ] [ Designated as safety issue: Yes ]The Number of Participants Discontinuing from the Study Due to non-steroidal antiinflammatory drug (NSAID)-Associated Upper GI Adverse Events or to Duodenal Ulcer during the treatment period
- The Number of Participants Developing Duodenal Ulcers Throughout 6 Months of Treatment [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]The Number of Participants Developing Duodenal Ulcers at any time during the 6 Months of the treatment period
- Heartburn Symptom Resolution, ie no Heartburn Symptoms During the Last 7 Days Prior to the Visit [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
Subjects were asked whether heartburn symptoms within the 7 days prior to the visit were:
- none: no symptoms
- mild: awareness of symptom, but easily tolerated
- moderate: discomforting symptom sufficient to cause interference with normal activities (including sleep)
- severe: incapacitating symptom, with inability to perform normal activities (including sleep) Heartburn was defined as a burning feeling rising from the stomach or lower part of the chest towards the neck.
- 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 ] [ Designated as 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. Subjects were asked: "since treatment started, has there been any change in your upper abdominal pain and/or discomfort?" Answers would be better/about the same/worse. Participants with the response "better" (instead of "about the same" or "worse"), are tabulated by treatment group.
- Mean Change From Baseline on Pain Intensity of the Severity of Dyspepsia Assessment (SODA) Subscales [ Time Frame: baseline to 6 Months ] [ Designated as safety issue: Yes ]Mean Change from Baseline on Pain Intensity of the Severity of Dyspepsia Assessment (SODA) Subscales. There are 6 questions about abdominal pain during the past 7 days: q 1-5 on average: 1. rate with a number between 0 (no pain) and 100 (pain as bad as it could be), 2. rate with a number between 0 (no discomfort) and 10 (discomfort as bad as it can be), 3. on a scale of 5 (from none to excriciating), 4. on 100 mm VAS, 5. on a scale of 4 and 6. worst abdominal pain scale 0 (no discomfort) and 10 (discomfort as bad as it can be). Total composite possible range for "pain intensity" is: 2-47
- Mean Change From Baseline on Non-Pain Symptoms of the Severity of Dyspepsia Assessment (SODA) Subscales [ Time Frame: baseline to 6 Months ] [ Designated as safety issue: Yes ]Change from Baseline of Non-Pain Symptoms on the SODA Assessment. There are 7 categories about the non-pain symptoms: burping/beching, heartburn, bloating, passing gas, sour taste, nausea and bad breath. For each of these categories, subjects were to rate during the past seven days, on average, the severity on a 5 point scale ranging from no problem to very severe problem. The scores are combined into a single composite score. The total possible range of the non-pain symptoms subscale is: 7-35.
- Mean Change From Baseline on Satisfaction of the Severity of Dyspepsia Assessment (SODA) Subscales [ Time Frame: baseline to 6 Months ] [ Designated as safety issue: Yes ]Mean Change in Satisfaction on SODA Assessment. Questions/statements to rate about satisfaction/dissatisfaction with their present level of abdominal discomfort. Question 1: 4-point scale range 0 (extremely unhappy) to 4 (extremely happy), statement 2 (I feel satisfied with my health with regard to abdominal discomfort) & statement 3 (I am pleased because my abdominal discomfort seems under control) on a 5 point scale (definitely true to definitely false) & question 4 rated how pleased subjects were with abdominal discomfort on a 10 point scale. Total satisfaction composite range: 2-23
|Study Start Date:||September 2007|
|Study Completion Date:||October 2008|
|Primary Completion Date:||October 2008 (Final data collection date for primary outcome measure)|
Naproxen 500 mg/Immediate-Release Esomeprazole 20 mg dosed twice daily
Drug: PN400 (VIMOVO)
PN400 tablets (Naproxen 500 mg and Esomeprazole 20 mg) twice daily (bid) taken orally.
Other Name: Vimovo
Active Comparator: Naproxen
Naproxen 500 mg dosed twice daily
Naproxen (500 mg) dosed twice daily (bid) orally
Other Name: Naprosyn
Primary: To demonstrate that PN400 is effective in reducing the risk of gastric ulcers in subjects at risk for developing NSAID-associated gastric ulcers.
- 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