Trial Outcomes & Findings for Evaluating PN 400 (VIMOVO) in Reducing Gastric Ulcers Compared to Non-steroidal Antiinflammatory Drug (NSAID) Naproxen (NCT NCT00527787)

Last Updated: 2010-12-28

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

434 participants

Primary outcome timeframe

6 months

Results posted on

2010-12-28

Participant Flow

A multi-center US study in which 59 sites recruited subjects between September 2007 and September 2008

Screening for eligibility and wash-out of restricted medications

Participant milestones

Participant milestones
Measure	PN400 (VIMOVO) Naproxen 500 mg/Immediate-Release Esomeprazole 20 mg	Naproxen Naproxen 500 mg
Overall Study STARTED	218	216
Overall Study COMPLETED	180	153
Overall Study NOT COMPLETED	38	63

Reasons for withdrawal

Reasons for withdrawal
Measure	PN400 (VIMOVO) Naproxen 500 mg/Immediate-Release Esomeprazole 20 mg	Naproxen Naproxen 500 mg
Overall Study Adverse Event	14	24
Overall Study Withdrawal by Subject	13	25
Overall Study Lost to Follow-up	5	2
Overall Study Duodenal Ulcer	1	10
Overall Study misc	5	2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PN400 (VIMOVO) n=218 Participants Naproxen 500 mg/Immediate-Release Esomeprazole 20 mg	Naproxen n=216 Participants Naproxen 500 mg	Total n=434 Participants Total of all reporting groups
Age Continuous	60.8 years STANDARD_DEVIATION 8.8 • n=5 Participants	61.9 years STANDARD_DEVIATION 8.5 • n=7 Participants	61.3 years STANDARD_DEVIATION 8.6 • n=5 Participants
Sex: Female, Male Female	150 Participants n=5 Participants	149 Participants n=7 Participants	299 Participants n=5 Participants
Sex: Female, Male Male	68 Participants n=5 Participants	67 Participants n=7 Participants	135 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months

Population: Intent to Treat (ITT) Population

Outcome measures

Outcome measures
Measure	PN400 (VIMOVO) n=218 Participants Naproxen 500 mg/Immediate-Release Esomeprazole 20 mg	Naproxen n=216 Participants Naproxen 500 mg
Number of Participants With Gastric Ulcer Confirmed by Endoscopy	9 Participants Interval 1.9 to 7.7	50 Participants Interval 17.7 to 29.4

SECONDARY outcome

Timeframe: 6 months

Population: Intent to Treat (ITT) Population

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

Outcome measures

Outcome measures
Measure	PN400 (VIMOVO) n=218 Participants Naproxen 500 mg/Immediate-Release Esomeprazole 20 mg	Naproxen n=216 Participants Naproxen 500 mg
The Number of Participants With Pre-Specified NSAID-Associated Upper GI Adverse Events or Duodenal Ulcers	114 Participants Interval 45.4 to 59.1	149 Participants Interval 62.4 to 75.1

SECONDARY outcome

Timeframe: 6 Months

Population: Intention to Treat (ITT) Population

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

Outcome measures

Outcome measures
Measure	PN400 (VIMOVO) n=218 Participants Naproxen 500 mg/Immediate-Release Esomeprazole 20 mg	Naproxen n=216 Participants Naproxen 500 mg
The Number of Participants Discontinuing From the Study Due to NSAID-Associated Upper GI Adverse Events or to Duodenal Ulcer	7 Participants Interval 1.3 to 6.5	26 Participants Interval 8.0 to 17.1

SECONDARY outcome

Timeframe: 6 months

Population: Intent to treat (ITT) population

The Number of Participants Developing Duodenal Ulcers at any time during the 6 Months of the treatment period

Outcome measures

Outcome measures
Measure	PN400 (VIMOVO) n=218 Participants Naproxen 500 mg/Immediate-Release Esomeprazole 20 mg	Naproxen n=216 Participants Naproxen 500 mg
The Number of Participants Developing Duodenal Ulcers Throughout 6 Months of Treatment	1 Participants Interval 0.0 to 2.5	11 Participants Interval 2.6 to 8.9

SECONDARY outcome

Timeframe: 6 months

Population: Intent to Treat (ITT) Population

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.

Outcome measures

Outcome measures
Measure	PN400 (VIMOVO) n=218 Participants Naproxen 500 mg/Immediate-Release Esomeprazole 20 mg	Naproxen n=216 Participants Naproxen 500 mg
Heartburn Symptom Resolution, ie no Heartburn Symptoms During the Last 7 Days Prior to the Visit	140 participants	65 participants

SECONDARY outcome

Timeframe: change from baseline at 6 Months

Population: Intent to Treat (ITT) Population

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.

Outcome measures

Outcome measures
Measure	PN400 (VIMOVO) n=218 Participants Naproxen 500 mg/Immediate-Release Esomeprazole 20 mg	Naproxen n=216 Participants Naproxen 500 mg
Improvement From Baseline in Upper Abdominal Pain and Discomfort Scores at 6 Months, Based on the Overall Treatment Evaluation for Dyspepsia Questionnaire	93 Participants	52 Participants

SECONDARY outcome

Timeframe: baseline to 6 Months

Population: Intent to Treat (ITT) Population

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

Outcome measures

Outcome measures
Measure	PN400 (VIMOVO) n=218 Participants Naproxen 500 mg/Immediate-Release Esomeprazole 20 mg	Naproxen n=216 Participants Naproxen 500 mg
Mean Change From Baseline on Pain Intensity of the Severity of Dyspepsia Assessment (SODA) Subscales	-6 Units on SODA Subscale Standard Error 0.7	0 Units on SODA Subscale Standard Error 0.7

SECONDARY outcome

Timeframe: baseline to 6 Months

Population: Intent to Treat (ITT) Population

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.

Outcome measures

Outcome measures
Measure	PN400 (VIMOVO) n=218 Participants Naproxen 500 mg/Immediate-Release Esomeprazole 20 mg	Naproxen n=216 Participants Naproxen 500 mg
Mean Change From Baseline on Non-Pain Symptoms of the Severity of Dyspepsia Assessment (SODA) Subscales	-2.2 Units on SODA Subscale Standard Error 0.3	-0.5 Units on SODA Subscale Standard Error 0.3

SECONDARY outcome

Timeframe: baseline to 6 Months

Population: Intent to Treat (ITT) Population

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

Outcome measures

Outcome measures
Measure	PN400 (VIMOVO) n=218 Participants Naproxen 500 mg/Immediate-Release Esomeprazole 20 mg	Naproxen n=216 Participants Naproxen 500 mg
Mean Change From Baseline on Satisfaction of the Severity of Dyspepsia Assessment (SODA) Subscales	3.4 Units on SODA Subscale Standard Error 0.4	0.9 Units on SODA Subscale Standard Error 0.4

Adverse Events

PN400 (VIMOVO)

Serious events: 5 serious events

Other events: 170 other events

Deaths: 0 deaths

Naproxen

Serious events: 6 serious events

Other events: 176 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	PN400 (VIMOVO) n=218 participants at risk Naproxen 500 mg/Immediate-Release Esomeprazole 20 mg	Naproxen n=216 participants at risk Naproxen 500 mg
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.46% 1/218 • Number of events 1 • Randomization through 6 months	0.00% 0/216 • Randomization through 6 months
Musculoskeletal and connective tissue disorders Osteoarthritis	0.46% 1/218 • Number of events 1 • Randomization through 6 months	0.00% 0/216 • Randomization through 6 months
Cardiac disorders Angina unstable	0.46% 1/218 • Number of events 1 • Randomization through 6 months	0.00% 0/216 • Randomization through 6 months
Cardiac disorders Myocardial infarction	0.46% 1/218 • Number of events 1 • Randomization through 6 months	0.00% 0/216 • Randomization through 6 months
Cardiac disorders Coronary artery disease	0.00% 0/218 • Randomization through 6 months	0.46% 1/216 • Number of events 1 • Randomization through 6 months
Gastrointestinal disorders Colitis ischemic	0.46% 1/218 • Number of events 1 • Randomization through 6 months	0.00% 0/216 • Randomization through 6 months
Gastrointestinal disorders Duodenal ulcer hemorrhage	0.00% 0/218 • Randomization through 6 months	0.46% 1/216 • Number of events 1 • Randomization through 6 months
General disorders Non-cardiac chest pain	0.46% 1/218 • Number of events 1 • Randomization through 6 months	0.46% 1/216 • Number of events 1 • Randomization through 6 months
Infections and infestations Clostridium difficile colitis	0.00% 0/218 • Randomization through 6 months	0.46% 1/216 • Number of events 1 • Randomization through 6 months
Infections and infestations Diverticulitis	0.00% 0/218 • Randomization through 6 months	0.46% 1/216 • Number of events 1 • Randomization through 6 months
Infections and infestations Post-procedural infection	0.00% 0/218 • Randomization through 6 months	0.46% 1/216 • Number of events 1 • Randomization through 6 months

Other adverse events

Other adverse events
Measure	PN400 (VIMOVO) n=218 participants at risk Naproxen 500 mg/Immediate-Release Esomeprazole 20 mg	Naproxen n=216 participants at risk Naproxen 500 mg
Gastrointestinal disorders Gastritis erosive	20.6% 45/218 • Number of events 45 • Randomization through 6 months	37.5% 81/216 • Number of events 81 • Randomization through 6 months
Gastrointestinal disorders Gastritis	17.9% 39/218 • Number of events 39 • Randomization through 6 months	13.0% 28/216 • Number of events 28 • Randomization through 6 months
Gastrointestinal disorders Dyspepsia	16.5% 36/218 • Number of events 36 • Randomization through 6 months	30.1% 65/216 • Number of events 65 • Randomization through 6 months
Gastrointestinal disorders Diarrhoea	6.4% 14/218 • Number of events 14 • Randomization through 6 months	6.0% 13/216 • Number of events 13 • Randomization through 6 months
Gastrointestinal disorders Abdominal distension	5.0% 11/218 • Number of events 11 • Randomization through 6 months	4.6% 10/216 • Number of events 10 • Randomization through 6 months
Gastrointestinal disorders Abdominal pain upper	4.1% 9/218 • Number of events 9 • Randomization through 6 months	8.3% 18/216 • Number of events 18 • Randomization through 6 months
Gastrointestinal disorders Flatulence	4.1% 9/218 • Number of events 9 • Randomization through 6 months	4.2% 9/216 • Number of events 9 • Randomization through 6 months
Gastrointestinal disorders Nausea	4.1% 9/218 • Number of events 9 • Randomization through 6 months	5.1% 11/216 • Number of events 11 • Randomization through 6 months
Gastrointestinal disorders Hiatus hernia	3.7% 8/218 • Number of events 8 • Randomization through 6 months	6.5% 14/216 • Number of events 14 • Randomization through 6 months
Gastrointestinal disorders Oesophagitis	3.2% 7/218 • Number of events 7 • Randomization through 6 months	7.9% 17/216 • Number of events 17 • Randomization through 6 months
Gastrointestinal disorders Abdominal pain lower	2.3% 5/218 • Number of events 5 • Randomization through 6 months	1.9% 4/216 • Number of events 4 • Randomization through 6 months
Infections and infestations Bronchitis	2.8% 6/218 • Number of events 6 • Randomization through 6 months	1.9% 4/216 • Number of events 4 • Randomization through 6 months
Infections and infestations Urinary tract infection	2.8% 6/218 • Number of events 6 • Randomization through 6 months	0.46% 1/216 • Number of events 1 • Randomization through 6 months
Infections and infestations Upper respiratory tract infection	2.3% 5/218 • Number of events 5 • Randomization through 6 months	3.7% 8/216 • Number of events 8 • Randomization through 6 months
Nervous system disorders Headache	2.8% 6/218 • Number of events 6 • Randomization through 6 months	0.93% 2/216 • Number of events 2 • Randomization through 6 months
Musculoskeletal and connective tissue disorders Muscle spasms	2.8% 6/218 • Number of events 6 • Randomization through 6 months	0.00% 0/216 • Randomization through 6 months
Respiratory, thoracic and mediastinal disorders Cough	2.8% 6/218 • Number of events 6 • Randomization through 6 months	2.8% 6/216 • Number of events 6 • Randomization through 6 months
Gastrointestinal disorders Abdominal pain	1.8% 4/218 • Number of events 4 • Randomization through 6 months	2.3% 5/216 • Number of events 5 • Randomization through 6 months
Gastrointestinal disorders Constipation	1.8% 4/218 • Number of events 4 • Randomization through 6 months	3.2% 7/216 • Number of events 7 • Randomization through 6 months
Gastrointestinal disorders Duodenitis	1.8% 4/218 • Number of events 4 • Randomization through 6 months	8.8% 19/216 • Number of events 19 • Randomization through 6 months
Gastrointestinal disorders Erosive duodenitis	1.8% 4/218 • Number of events 4 • Randomization through 6 months	13.9% 30/216 • Number of events 30 • Randomization through 6 months
Gastrointestinal disorders Abdominal discomfort	1.4% 3/218 • Number of events 3 • Randomization through 6 months	2.8% 6/216 • Number of events 6 • Randomization through 6 months
Gastrointestinal disorders Gastrooesophageal reflux disease	0.46% 1/218 • Number of events 1 • Randomization through 6 months	3.2% 7/216 • Number of events 7 • Randomization through 6 months
Gastrointestinal disorders Erosive oesophagitis	0.00% 0/218 • Randomization through 6 months	5.6% 12/216 • Number of events 12 • Randomization through 6 months
Infections and infestations Nasopharyngitis	0.92% 2/218 • Number of events 2 • Randomization through 6 months	3.7% 8/216 • Number of events 8 • Randomization through 6 months

Additional Information

Senior Vice President, Clinical Research

POZEN Inc

Phone: 919-913-1030

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee PI agrees that the first publication will be a multi-center publication of the study results. Following this multi-center publication, PI can publish, present or use any non-confidential results following Sponsor review and comment.
Publication restrictions are in place

Restriction type: OTHER