Trial Outcomes & Findings for Evaluating PN 400 (VIMOVO) in Reducing Gastric Ulcers Compared to Non-steroidal Antiinflammatory Drug (NSAID) Naproxen (NCT NCT01129011)

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

420 participants

Primary outcome timeframe

6 months

Results posted on

2010-12-28

Participant Flow

A multi-center US study in which 70 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 dosed twice daily (bid)	Naproxen Naproxen 500 mg dosed twice daily (bid)
Overall Study STARTED	210	210
Overall Study COMPLETED	151	153
Overall Study NOT COMPLETED	59	57

Reasons for withdrawal

Reasons for withdrawal
Measure	PN400 (VIMOVO) Naproxen 500 mg/Immediate-Release Esomeprazole 20 mg dosed twice daily (bid)	Naproxen Naproxen 500 mg dosed twice daily (bid)
Overall Study Adverse Event	20	30
Overall Study Withdrawal by Subject	24	8
Overall Study Lost to Follow-up	6	7
Overall Study Duodenal Ulcer	2	8
Overall Study misc	7	4

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=210 Participants Naproxen 500 mg/Immediate-Release Esomeprazole 20 mg dosed twice daily (bid)	Naproxen n=210 Participants Naproxen 500 mg dosed twice daily (bid)	Total n=420 Participants Total of all reporting groups
Age Continuous	59.6 years STANDARD_DEVIATION 8.2 • n=5 Participants	59.4 years STANDARD_DEVIATION 8.3 • n=7 Participants	59.5 years STANDARD_DEVIATION 8.2 • n=5 Participants
Sex: Female, Male Female	132 Participants n=5 Participants	142 Participants n=7 Participants	274 Participants n=5 Participants
Sex: Female, Male Male	78 Participants n=5 Participants	68 Participants n=7 Participants	146 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months

Population: Intent to Treat (ITT) Population

Outcome measures

Outcome measures
Measure	PN400 (VIMOVO) n=210 Participants Naproxen 500 mg/Immediate-Release Esomeprazole 20 mg dosed twice daily (bid)	Naproxen n=210 Participants Naproxen 500 mg dosed twice daily (bid)
Number of Participants With Gastric Ulcer Confirmed by Endoscopy	15 Participants Interval 4.1 to 11.5	51 Participants Interval 18.6 to 30.7

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=210 Participants Naproxen 500 mg/Immediate-Release Esomeprazole 20 mg dosed twice daily (bid)	Naproxen n=210 Participants Naproxen 500 mg dosed twice daily (bid)
The Number of Participants With Pre-Specified NSAID-Associated Upper GI Adverse Events or Duodenal Ulcers	114 Participants Interval 47.3 to 61.2	151 Participants Interval 65.3 to 77.9

SECONDARY outcome

Timeframe: 6 Months

Population: Intent 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=210 Participants Naproxen 500 mg/Immediate-Release Esomeprazole 20 mg dosed twice daily (bid)	Naproxen n=210 Participants Naproxen 500 mg dosed twice daily (bid)
The Number of Participants Discontinuing From the Study Due to NSAID-Associated Upper GI Adverse Events or to Duodenal Ulcer	10 Participants Interval 2.3 to 8.6	25 Participants Interval 7.9 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=210 Participants Naproxen 500 mg/Immediate-Release Esomeprazole 20 mg dosed twice daily (bid)	Naproxen n=210 Participants Naproxen 500 mg dosed twice daily (bid)
The Number of Participants Developing Duodenal Ulcers Throughout 6 Months of Treatment	2 Participants Interval 0.1 to 3.4	12 Participants Interval 3.0 to 9.8

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=210 Participants Naproxen 500 mg/Immediate-Release Esomeprazole 20 mg dosed twice daily (bid)	Naproxen n=210 Participants Naproxen 500 mg dosed twice daily (bid)
Heartburn Symptom Resolution, ie no Heartburn Symptoms During the Last 7 Days Prior to the Visit	102 participants	62 participants

SECONDARY outcome

Timeframe: change from baseline at 6 Months

Population: Intent to Treat 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=210 Participants Naproxen 500 mg/Immediate-Release Esomeprazole 20 mg dosed twice daily (bid)	Naproxen n=210 Participants Naproxen 500 mg dosed twice daily (bid)
Improvement From Baseline in Upper Abdominal Pain and Discomfort Scores at 6 Months, Based on the Overall Treatment Evaluation for Dyspepsia Questionnaire	79 Participants	63 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=210 Participants Naproxen 500 mg/Immediate-Release Esomeprazole 20 mg dosed twice daily (bid)	Naproxen n=210 Participants Naproxen 500 mg dosed twice daily (bid)
Mean Change From Baseline on Pain Intensity of the Severity of Dyspepsia Assessment (SODA) Subscales	-3 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=210 Participants Naproxen 500 mg/Immediate-Release Esomeprazole 20 mg dosed twice daily (bid)	Naproxen n=210 Participants Naproxen 500 mg dosed twice daily (bid)
Mean Change From Baseline on Non-Pain Symptoms of the Severity of Dyspepsia Assessment (SODA) Subscales	-1.1 Units on SODA Subscale Standard Error 0.3	0.1 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=210 Participants Naproxen 500 mg/Immediate-Release Esomeprazole 20 mg dosed twice daily (bid)	Naproxen n=210 Participants Naproxen 500 mg dosed twice daily (bid)
Mean Change From Baseline on Satisfaction of the Severity of Dyspepsia Assessment (SODA) Subscales	1.9 Units on SODA Subscale Standard Error 0.4	0.5 Units on SODA Subscale Standard Error 0.4

Adverse Events

PN400 (VIMOVO)

Serious events: 5 serious events

Other events: 160 other events

Deaths: 0 deaths

Naproxen

Serious events: 7 serious events

Other events: 174 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	PN400 (VIMOVO) n=210 participants at risk Naproxen 500 mg/Immediate-Release Esomeprazole 20 mg dosed twice daily (bid)	Naproxen n=210 participants at risk Naproxen 500 mg dosed twice daily (bid)
Cardiac disorders Atrial flutter	0.48% 1/210 • Number of events 1 • Randomization through 6 months	0.00% 0/210 • Randomization through 6 months
Cardiac disorders Palpitations	0.00% 0/210 • Randomization through 6 months	0.48% 1/210 • Number of events 1 • Randomization through 6 months
Injury, poisoning and procedural complications Post-procedural hemorrhage	0.48% 1/210 • Number of events 1 • Randomization through 6 months	0.00% 0/210 • Randomization through 6 months
Injury, poisoning and procedural complications Concussion	0.00% 0/210 • Randomization through 6 months	0.48% 1/210 • Number of events 1 • Randomization through 6 months
Injury, poisoning and procedural complications Fracture	0.00% 0/210 • Randomization through 6 months	0.48% 1/210 • Number of events 1 • Randomization through 6 months
Injury, poisoning and procedural complications Upper limb fracture	0.00% 0/210 • Randomization through 6 months	0.48% 1/210 • Number of events 1 • Randomization through 6 months
Nervous system disorders Syncope	0.48% 1/210 • Number of events 1 • Randomization through 6 months	0.00% 0/210 • Randomization through 6 months
Psychiatric disorders Suicide attempt	0.48% 1/210 • Number of events 1 • Randomization through 6 months	0.00% 0/210 • Randomization through 6 months
Surgical and medical procedures Mastectomy	0.48% 1/210 • Number of events 1 • Randomization through 6 months	0.00% 0/210 • Randomization through 6 months
Infections and infestations Pneumonia	0.00% 0/210 • Randomization through 6 months	0.48% 1/210 • Number of events 1 • Randomization through 6 months
Infections and infestations Urinary tract infection	0.00% 0/210 • Randomization through 6 months	0.48% 1/210 • Number of events 1 • Randomization through 6 months
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/210 • Randomization through 6 months	0.48% 1/210 • Number of events 1 • Randomization through 6 months
Skin and subcutaneous tissue disorders Diabetic ulcer	0.00% 0/210 • Randomization through 6 months	0.48% 1/210 • Number of events 1 • Randomization through 6 months

Other adverse events

Other adverse events
Measure	PN400 (VIMOVO) n=210 participants at risk Naproxen 500 mg/Immediate-Release Esomeprazole 20 mg dosed twice daily (bid)	Naproxen n=210 participants at risk Naproxen 500 mg dosed twice daily (bid)
Gastrointestinal disorders Dyspepsia	19.5% 41/210 • Number of events 41 • Randomization through 6 months	23.3% 49/210 • Number of events 49 • Randomization through 6 months
Gastrointestinal disorders Gastritis erosive	18.1% 38/210 • Number of events 38 • Randomization through 6 months	38.6% 81/210 • Number of events 81 • Randomization through 6 months
Gastrointestinal disorders Gastritis	16.2% 34/210 • Number of events 34 • Randomization through 6 months	15.2% 32/210 • Number of events 32 • Randomization through 6 months
Gastrointestinal disorders Abdominal pain upper	7.1% 15/210 • Number of events 15 • Randomization through 6 months	9.0% 19/210 • Number of events 19 • Randomization through 6 months
Gastrointestinal disorders Nausea	6.2% 13/210 • Number of events 13 • Randomization through 6 months	4.8% 10/210 • Number of events 10 • Randomization through 6 months
Gastrointestinal disorders Diarrhoea	5.7% 12/210 • Number of events 12 • Randomization through 6 months	4.3% 9/210 • Number of events 9 • Randomization through 6 months
Gastrointestinal disorders Hiatus hernia	4.8% 10/210 • Number of events 10 • Randomization through 6 months	5.2% 11/210 • Number of events 11 • Randomization through 6 months
Gastrointestinal disorders Oesophagitis	3.8% 8/210 • Number of events 8 • Randomization through 6 months	7.1% 15/210 • Number of events 15 • Randomization through 6 months
Gastrointestinal disorders Constipation	3.3% 7/210 • Number of events 7 • Randomization through 6 months	2.4% 5/210 • Number of events 5 • Randomization through 6 months
Gastrointestinal disorders Flatulence	3.3% 7/210 • Number of events 7 • Randomization through 6 months	1.9% 4/210 • Number of events 4 • Randomization through 6 months
Gastrointestinal disorders Abdominal pain	2.9% 6/210 • Number of events 6 • Randomization through 6 months	0.95% 2/210 • Number of events 2 • Randomization through 6 months
Gastrointestinal disorders Abdominal distension	2.4% 5/210 • Number of events 5 • Randomization through 6 months	2.9% 6/210 • Number of events 6 • Randomization through 6 months
Gastrointestinal disorders Erosive duodenitis	2.4% 5/210 • Number of events 5 • Randomization through 6 months	9.5% 20/210 • Number of events 20 • Randomization through 6 months
Gastrointestinal disorders Abdominal pain lower	1.9% 4/210 • Number of events 4 • Randomization through 6 months	3.3% 7/210 • Number of events 7 • Randomization through 6 months
Gastrointestinal disorders Gastrooesophageal reflux disease	1.4% 3/210 • Number of events 3 • Randomization through 6 months	3.8% 8/210 • Number of events 8 • Randomization through 6 months
Gastrointestinal disorders Duodenitis	0.95% 2/210 • Number of events 2 • Randomization through 6 months	5.7% 12/210 • Number of events 12 • Randomization through 6 months
Gastrointestinal disorders Erosive oesophagitis	0.95% 2/210 • Number of events 2 • Randomization through 6 months	5.7% 12/210 • Number of events 12 • Randomization through 6 months
Gastrointestinal disorders Gastritis haemorrhagic	0.48% 1/210 • Number of events 1 • Randomization through 6 months	2.9% 6/210 • Number of events 6 • Randomization through 6 months
Infections and infestations Upper respiratory tract infection	7.6% 16/210 • Number of events 16 • Randomization through 6 months	3.8% 8/210 • Number of events 8 • Randomization through 6 months
Infections and infestations Sinusitis	2.4% 5/210 • Number of events 5 • Randomization through 6 months	2.9% 6/210 • Number of events 6 • Randomization through 6 months
Infections and infestations Urinary tract infection	1.9% 4/210 • Number of events 4 • Randomization through 6 months	2.4% 5/210 • Number of events 5 • Randomization through 6 months
Musculoskeletal and connective tissue disorders Back pain	2.4% 5/210 • Number of events 5 • Randomization through 6 months	1.4% 3/210 • Number of events 3 • Randomization through 6 months
Musculoskeletal and connective tissue disorders Arthralgia	0.95% 2/210 • Number of events 2 • Randomization through 6 months	3.8% 8/210 • Number of events 8 • Randomization through 6 months
Nervous system disorders Dysgeusia	2.4% 5/210 • Number of events 5 • Randomization through 6 months	1.9% 4/210 • Number of events 4 • Randomization through 6 months
Nervous system disorders Headache	2.4% 5/210 • Number of events 5 • Randomization through 6 months	1.9% 4/210 • Number of events 4 • Randomization through 6 months
Respiratory, thoracic and mediastinal disorders Cough	1.9% 4/210 • Number of events 4 • Randomization through 6 months	2.4% 5/210 • Number of events 5 • Randomization through 6 months

Additional Information

Senior Vice President, Clinical Research

POZEN

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 study results following Sponsor review and comment.
Publication restrictions are in place

Restriction type: OTHER