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A Study to Evaluate the Incidence of Gastric Ulcers Following Administration of Either PA32540 or Enteric Coated Aspirin 325 mg in Subjects Who Are at Risk for Developing Aspirin-Associated Ulcers

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ClinicalTrials.gov Identifier: NCT00961350
Recruitment Status : Completed
First Posted : August 18, 2009
Results First Posted : January 21, 2016
Last Update Posted : February 18, 2016
Sponsor:
Information provided by (Responsible Party):
POZEN

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Gastric Ulcer
Interventions Drug: PA32540
Drug: EC Aspirin 325
Enrollment 530
Recruitment Details  
Pre-assignment Details  
Arm/Group Title PA32540 EC Aspirin
Hide Arm/Group Description PA32540 tablets contain 325 mg enteric coated (EC) aspirin and 40 mg immediate-release omeprazole dosed once daily (QD) EC Aspirin 325 mg enteric coated tablet (PA32540 minus omeprazole) dosed once daily (QD)
Period Title: Overall Study
Started 265 265
Intent-to-Treat Population (ITT) 265 265
Safety Population 264 [1] 265
Completed 218 198
Not Completed 47 67
Reason Not Completed
Adverse Event             18             33
Withdrawal by Subject             10             10
Lost to Follow-up             3             3
Misc             16             21
[1]
1. One sub rand to PA32540 took EC-Aspirin
Arm/Group Title PA32540 EC Aspirin Total
Hide Arm/Group Description PA32540 tablets contain 325 mg enteric coated (EC) aspirin and 40 mg immediate-release omeprazole dosed once daily (QD) EC Aspirin 325 mg enteric coated tablet (PA32540 minus omeprazole) dosed once daily (QD) Total of all reporting groups
Overall Number of Baseline Participants 265 265 530
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 265 participants 265 participants 530 participants
66.3  (7.2) 65.8  (6.7) 66.1  (6.96)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 265 participants 265 participants 530 participants
Female
77
  29.1%
75
  28.3%
152
  28.7%
Male
188
  70.9%
190
  71.7%
378
  71.3%
1.Primary Outcome
Title Number of Participants With Gastric Ulcer Confirmed by Endoscopy(EC) Aspirin 325 mg
Hide Description 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.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) Population
Arm/Group Title PA32540 EC Aspirin
Hide Arm/Group Description:
PA32540 tablets contain 325 mg enteric coated (EC) aspirin and 40 mg immediate-release omeprazole dosed once daily (QD)
EC Aspirin 325 mg enteric coated tablet (PA32540 minus omeprazole) dosed once daily (QD)
Overall Number of Participants Analyzed 265 265
Measure Type: Number
Unit of Measure: participants
10 23
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PA32540, EC Aspirin
Comments The primary efficacy endpoint was the proportion of subjects with gastric ulcers throughout 6 months of treatment. The primary endpoint was analyzed with the CMH test stratified by NSAID use (COX-2/Other NSAID/No) at randomization. A sample size of 250 subjects/treatment would provide 86% power to detect the difference of 8% between EC aspirin 325 mg (13%) and PA32540 (5%) with a 2-sided significance of 5%; and, provides adequate power to test the key secondary endpoints in sequential order.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.020
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments CMH test stratified by NSAID use=COX-2, other NSAID, or NSAID use=NO at randomization.
Method of Estimation Estimation Parameter Proportions
Estimated Value 3.8
Confidence Interval 95%
1.8 to 6.8
Estimation Comments The proportion is from the PA32540 treatment group.
2.Secondary Outcome
Title The Number of Participants With Gastric and/or Duodenal Ulcers
Hide Description The Number of Participants with Gastric and/or Duodenal Ulcers throughout 6 months of treatment.
Time Frame 6 Months
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) Population
Arm/Group Title PA32540 EC Aspirin
Hide Arm/Group Description:
PA32540 tablets contain 325 mg enteric coated (EC) aspirin and 40 mg immediate-release omeprazole dosed once daily (QD)
EC Aspirin 325 mg enteric coated tablet (PA32540 minus omeprazole) dosed once daily (QD)
Overall Number of Participants Analyzed 265 265
Measure Type: Number
Unit of Measure: participants
11 31
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PA32540, EC Aspirin
Comments The cumulative proportion of subjects developing gastric ulcers and/or duodenal ulcers at 6 months was analyzed using the CMH test stratified by NSAID use=COX-2, other NSAID, or NSAID use=NO at randomization.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments CMH test stratified by NSAID use=COX-2, other NSAID, or NSAID use=NO at randomization.
3.Secondary Outcome
Title The Number of Subjects With “Treatment Success”
Hide Description Those Subjects Without Gastric Ulcers and Without Upper Gastrointestinal (UGI) Adverse Events leading to discontinuation.
Time Frame 6 Months
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat Population
Arm/Group Title PA32540 EC Aspirin
Hide Arm/Group Description:
PA32540 tablets contain 325 mg enteric coated (EC) aspirin and 40 mg immediate-release omeprazole dosed once daily (QD)
EC Aspirin 325 mg enteric coated tablet (PA32540 minus omeprazole) dosed once daily (QD)
Overall Number of Participants Analyzed 265 265
Measure Type: Number
Unit of Measure: participants
249 220
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PA32540, EC Aspirin
Comments The cumulative proportion of subjects with Treatment Success was analyzed using the CMH test stratified by NSAID use=COX-2, other NSAID, or NSAID use=NO at randomization.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments CMH test stratified by NSAID use=COX-2, other NSAID, or NSAID use=NO at randomization.
4.Secondary Outcome
Title The Number of Participants Discontinuing From the Study Due to NSAID-Associated Upper GI Adverse Events
Hide Description The Number of Participants Discontinuing from the Study Due to non-steroidal anti-inflammatory drug (NSAID)-Associated Upper GI Adverse Events during the treatment period
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) Population
Arm/Group Title PA32540 EC Aspirin
Hide Arm/Group Description:
PA32540 tablets contain 325 mg enteric coated (EC) aspirin and 40 mg immediate-release omeprazole dosed once daily (QD)
EC Aspirin 325 mg enteric coated tablet (PA32540 minus omeprazole) dosed once daily (QD)
Overall Number of Participants Analyzed 265 265
Measure Type: Number
Unit of Measure: participants
6 22
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PA32540, EC Aspirin
Comments The cumulative proportion of subjects discontinuing from the study due to NSAID-associated upper GI adverse events was analyzed using the CMH test stratified by NSAID use=COX-2, other NSAID, or NSAID use=NO at randomization.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments CMH test stratified by NSAID use=COX-2, other NSAID, or NSAID use=NO at randomization.
5.Secondary Outcome
Title The Number of Participants With Heartburn Resolution at 6 Months, ie no Heartburn Symptoms During the Last 7 Days Prior to the Visit
Hide Description

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.
Time Frame 6 Months
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) Population
Arm/Group Title PA32540 EC Aspirin
Hide Arm/Group Description:
PA32540 tablets contain 325 mg enteric coated (EC) aspirin and 40 mg immediate-release omeprazole dosed once daily (QD)
EC Aspirin 325 mg enteric coated tablet (PA32540 minus omeprazole) dosed once daily (QD)
Overall Number of Participants Analyzed 265 265
Measure Type: Number
Unit of Measure: participants
198 135
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PA32540, EC Aspirin
Comments The proportion of subjects who had no heartburn at 6 months (regardless of the presence or absence of heartburn at baseline) was analyzed using the CMH test stratified by NSAID use=COX-2, other NSAID, or NSAID use=NO at randomization.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments CMH test stratified by NSAID use=COX-2, other NSAID, or NSAID use=NO and by baseline heartburn severity at randomization.
Time Frame Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title PA32540 EC Aspirin
Hide Arm/Group Description PA32540 tablets contain 325 mg enteric coated (EC) aspirin and 40 mg immediate-release omeprazole dosed once daily (QD) EC Aspirin 325 mg enteric coated tablet (PA32540 minus omeprazole) dosed once daily (QD)
All-Cause Mortality
PA32540 EC Aspirin
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
PA32540 EC Aspirin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   16/264 (6.06%)      24/265 (9.06%)    
Cardiac disorders     
Angina pectoris  1  1/264 (0.38%)  1 1/265 (0.38%)  1
Atrial fibrillation  1  1/264 (0.38%)  1 1/265 (0.38%)  1
Atrial flutter  1  1/264 (0.38%)  1 1/265 (0.38%)  1
Coronary artery disease  1  1/264 (0.38%)  1 0/265 (0.00%)  0
Acute myocardial infarction  1  0/264 (0.00%)  0 2/265 (0.75%)  2
Coronary artery occlusion  1  0/264 (0.00%)  0 1/265 (0.38%)  1
Sudden cardiac death  1  0/264 (0.00%)  0 1/265 (0.38%)  1
Gastrointestinal disorders     
Abdominal pain  1  1/264 (0.38%)  1 0/265 (0.00%)  0
Abdominal pain upper  1  1/264 (0.38%)  1 0/265 (0.00%)  0
Gastric ulcer haemorrhage  1  1/264 (0.38%)  1 0/264 (0.00%)  0
Intestinal obstruction  1  1/264 (0.38%)  1 0/265 (0.00%)  0
Pancreatic cyst  1  1/264 (0.38%)  1 0/265 (0.00%)  0
Pancreatitis  1  1/264 (0.38%)  1 0/265 (0.00%)  0
Diverticulitis  1  0/264 (0.00%)  0 1/265 (0.38%)  1
Duodenal ulcer haemorrhage  1  0/264 (0.00%)  0 1/265 (0.38%)  1
Gastrooesophageal reflux disease  1  0/264 (0.00%)  0 1/265 (0.38%)  1
Intestinal haemorrhage  1  0/264 (0.00%)  0 1/265 (0.38%)  1
Pancreatitis acute  1  0/264 (0.00%)  0 1/265 (0.38%)  1
Small intestinal obstruction  1  0/264 (0.00%)  0 1/265 (0.38%)  1
General disorders     
Non-cardiac chest pain  1  4/264 (1.52%)  4 0/265 (0.00%)  0
Chest Pain  1  0/264 (0.00%)  0 1/265 (0.38%)  1
Infusion site extravasation  1  1/264 (0.38%)  1 0/265 (0.00%)  0
Hepatobiliary disorders     
Cholecystitis  1  1/264 (0.38%)  1 0/265 (0.00%)  0
Cholelithiasis  1  0/264 (0.00%)  0 1/265 (0.38%)  1
Infections and infestations     
Osteomyelitis  1  1/264 (0.38%)  2 0/265 (0.00%)  0
Wound infection  1  1/264 (0.38%)  1 0/265 (0.00%)  0
Chest wall abscess  1  0/264 (0.00%)  0 1/265 (0.38%)  1
Pneumonia  1  0/264 (0.00%)  0 1/265 (0.38%)  1
Sepsis syndrome  1  0/264 (0.00%)  0 1/265 (0.38%)  1
Urinary tract infection  1  0/264 (0.00%)  0 1/265 (0.38%)  1
Injury, poisoning and procedural complications     
Humerus fracture  1  1/264 (0.38%)  1 0/265 (0.00%)  0
Ankle fracture  1  0/264 (0.00%)  0 1/265 (0.38%)  1
Femur fracture  1  0/264 (0.00%)  0 1/265 (0.38%)  1
Joint dislocation  1  0/264 (0.00%)  0 1/265 (0.38%)  1
Metabolism and nutrition disorders     
Hyperglycemia  1  0/264 (0.00%)  0 1/265 (0.38%)  1
Musculoskeletal and connective tissue disorders     
Myofascial pain syndrome  1  0/264 (0.00%)  0 1/265 (0.38%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Colon cancer  1  1/264 (0.38%)  1 0/265 (0.00%)  0
Prostate cancer  1  1/264 (0.38%)  1 0/265 (0.00%)  0
Non-small cell lung cancer  1  0/264 (0.00%)  0 1/265 (0.38%)  1
Nervous system disorders     
Transient ischaemic attack  1  0/264 (0.00%)  0 1/265 (0.38%)  1
Renal and urinary disorders     
Azotaemia  1  1/264 (0.38%)  1 0/265 (0.00%)  0
Renal impairment  1  0/264 (0.00%)  0 1/265 (0.38%)  1
Respiratory, thoracic and mediastinal disorders     
Haemoptysis  1  1/264 (0.38%)  1 0/265 (0.00%)  0
Sleep apnoea syndrome  1  1/264 (0.38%)  1 0/265 (0.00%)  0
Respiratory failure  1  0/264 (0.00%)  0 1/265 (0.38%)  1
Vascular disorders     
Deep vein thrombosis  1  1/264 (0.38%)  1 1/265 (0.38%)  1
Aortic aneurysm  1  0/264 (0.00%)  0 1/265 (0.38%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (12.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
PA32540 EC Aspirin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   191/264 (72.35%)      224/265 (84.53%)    
Gastrointestinal disorders     
Gastritis  1  46/264 (17.42%)  51 44/265 (16.60%)  48
Dyspepsia  1  35/264 (13.26%)  40 90/265 (33.96%)  114
Gastritis erosive  1  27/264 (10.23%)  29 82/265 (30.94%)  97
Hiatus hernia  1  27/264 (10.23%)  27 26/265 (9.81%)  26
Duodenitis  1  15/264 (5.68%)  17 46/265 (17.36%)  47
Diarrhoea  1  9/264 (3.41%)  9 8/265 (3.02%)  8
Nausea  1  8/264 (3.03%)  8 7/265 (2.64%)  7
Oesophagitis  1  8/264 (3.03%)  8 31/265 (11.70%)  34
Gastrooesophageal reflux disease  1  7/264 (2.65%)  7 14/265 (5.28%)  15
Oesophageal disorder  1  7/264 (2.65%)  8 2/265 (0.75%)  2
Reflux oesophagitis  1  4/264 (1.52%)  4 7/265 (2.64%)  7
Erosive duodenitis  1  2/264 (0.76%)  2 25/265 (9.43%)  26
Duodenal ulcer  1  1/264 (0.38%)  1 9/265 (3.40%)  9
Erosive oesophagitis  1  1/264 (0.38%)  1 15/265 (5.66%)  15
Infections and infestations     
Upper respiratory tract infection  1  5/264 (1.89%)  5 10/265 (3.77%)  10
Nasopharyngitis  1  4/264 (1.52%)  5 6/265 (2.26%)  6
Bronchitis  1  3/264 (1.14%)  3 9/265 (3.40%)  9
Musculoskeletal and connective tissue disorders     
Arthralgia  1  2/264 (0.76%)  2 6/265 (2.26%)  9
Nervous system disorders     
Dizziness  1  4/264 (1.52%)  4 6/265 (2.26%)  6
Skin and subcutaneous tissue disorders     
Petechiae  1  3/264 (1.14%)  3 10/265 (3.77%)  13
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (12.1)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Name/Title: John Fort, MD / Chief Medical Officer
Organization: POZEN
Phone: 919-913-1030
Responsible Party: POZEN
ClinicalTrials.gov Identifier: NCT00961350     History of Changes
Other Study ID Numbers: PA32540-301
First Submitted: August 17, 2009
First Posted: August 18, 2009
Results First Submitted: October 22, 2015
Results First Posted: January 21, 2016
Last Update Posted: February 18, 2016