Trial Outcomes & Findings for 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 (NCT NCT00961350)

Last Updated: 2016-02-18

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

530 participants

Primary outcome timeframe

6 months

Results posted on

2016-02-18

Participant Flow

Participant milestones

Participant milestones
Measure	PA32540 PA32540 tablets contain 325 mg enteric coated (EC) aspirin and 40 mg immediate-release omeprazole dosed once daily (QD)	EC Aspirin EC Aspirin 325 mg enteric coated tablet (PA32540 minus omeprazole) dosed once daily (QD)
Overall Study STARTED	265	265
Overall Study Intent-to-Treat Population (ITT)	265	265
Overall Study Safety Population	264	265
Overall Study COMPLETED	218	198
Overall Study NOT COMPLETED	47	67

Reasons for withdrawal

Reasons for withdrawal
Measure	PA32540 PA32540 tablets contain 325 mg enteric coated (EC) aspirin and 40 mg immediate-release omeprazole dosed once daily (QD)	EC Aspirin EC Aspirin 325 mg enteric coated tablet (PA32540 minus omeprazole) dosed once daily (QD)
Overall Study Adverse Event	18	33
Overall Study Withdrawal by Subject	10	10
Overall Study Lost to Follow-up	3	3
Overall Study Misc	16	21

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PA32540 n=265 Participants PA32540 tablets contain 325 mg enteric coated (EC) aspirin and 40 mg immediate-release omeprazole dosed once daily (QD)	EC Aspirin n=265 Participants EC Aspirin 325 mg enteric coated tablet (PA32540 minus omeprazole) dosed once daily (QD)	Total n=530 Participants Total of all reporting groups
Age, Continuous	66.3 years STANDARD_DEVIATION 7.2 • n=5 Participants	65.8 years STANDARD_DEVIATION 6.7 • n=7 Participants	66.1 years STANDARD_DEVIATION 6.96 • n=5 Participants
Sex: Female, Male Female	77 Participants n=5 Participants	75 Participants n=7 Participants	152 Participants n=5 Participants
Sex: Female, Male Male	188 Participants n=5 Participants	190 Participants n=7 Participants	378 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months

Population: Intent to Treat (ITT) Population

Outcome measures

Outcome measures
Measure	PA32540 n=265 Participants PA32540 tablets contain 325 mg enteric coated (EC) aspirin and 40 mg immediate-release omeprazole dosed once daily (QD)	EC Aspirin n=265 Participants EC Aspirin 325 mg enteric coated tablet (PA32540 minus omeprazole) dosed once daily (QD)
Number of Participants With Gastric Ulcer Confirmed by Endoscopy(EC) Aspirin 325 mg	10 participants Interval 1.8 to 6.8	23 participants

SECONDARY outcome

Timeframe: 6 Months

Population: Intent to Treat (ITT) Population

The Number of Participants with Gastric and/or Duodenal Ulcers throughout 6 months of treatment.

Outcome measures

Outcome measures
Measure	PA32540 n=265 Participants PA32540 tablets contain 325 mg enteric coated (EC) aspirin and 40 mg immediate-release omeprazole dosed once daily (QD)	EC Aspirin n=265 Participants EC Aspirin 325 mg enteric coated tablet (PA32540 minus omeprazole) dosed once daily (QD)
The Number of Participants With Gastric and/or Duodenal Ulcers	11 participants	31 participants

SECONDARY outcome

Timeframe: 6 Months

Population: Intent to Treat Population

Those Subjects Without Gastric Ulcers and Without Upper Gastrointestinal (UGI) Adverse Events leading to discontinuation.

Outcome measures

Outcome measures
Measure	PA32540 n=265 Participants PA32540 tablets contain 325 mg enteric coated (EC) aspirin and 40 mg immediate-release omeprazole dosed once daily (QD)	EC Aspirin n=265 Participants EC Aspirin 325 mg enteric coated tablet (PA32540 minus omeprazole) dosed once daily (QD)
The Number of Subjects With "Treatment Success"	249 participants	220 participants

SECONDARY outcome

Timeframe: 6 months

Population: Intent to Treat (ITT) Population

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

Outcome measures

Outcome measures
Measure	PA32540 n=265 Participants PA32540 tablets contain 325 mg enteric coated (EC) aspirin and 40 mg immediate-release omeprazole dosed once daily (QD)	EC Aspirin n=265 Participants EC Aspirin 325 mg enteric coated tablet (PA32540 minus omeprazole) dosed once daily (QD)
The Number of Participants Discontinuing From the Study Due to NSAID-Associated Upper GI Adverse Events	6 participants	22 participants

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	PA32540 n=265 Participants PA32540 tablets contain 325 mg enteric coated (EC) aspirin and 40 mg immediate-release omeprazole dosed once daily (QD)	EC Aspirin n=265 Participants EC Aspirin 325 mg enteric coated tablet (PA32540 minus omeprazole) dosed once daily (QD)
The Number of Participants With Heartburn Resolution at 6 Months, ie no Heartburn Symptoms During the Last 7 Days Prior to the Visit	198 participants	135 participants

Adverse Events

PA32540

Serious events: 16 serious events

Other events: 191 other events

Deaths: 0 deaths

EC Aspirin

Serious events: 24 serious events

Other events: 224 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

John Fort, MD / Chief Medical Officer

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

Measure	PA32540 n=264 participants at risk PA32540 tablets contain 325 mg enteric coated (EC) aspirin and 40 mg immediate-release omeprazole dosed once daily (QD)	EC Aspirin n=265 participants at risk EC Aspirin 325 mg enteric coated tablet (PA32540 minus omeprazole) dosed once daily (QD)
Gastrointestinal disorders Abdominal pain	0.38% 1/264 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.00% 0/265 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Gastrointestinal disorders Abdominal pain upper	0.38% 1/264 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.00% 0/265 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Gastrointestinal disorders Gastric ulcer haemorrhage	0.38% 1/264 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.00% 0/264 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Gastrointestinal disorders Intestinal obstruction	0.38% 1/264 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.00% 0/265 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Gastrointestinal disorders Pancreatic cyst	0.38% 1/264 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.00% 0/265 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Gastrointestinal disorders Pancreatitis	0.38% 1/264 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.00% 0/265 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Gastrointestinal disorders Diverticulitis	0.00% 0/264 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.38% 1/265 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Gastrointestinal disorders Duodenal ulcer haemorrhage	0.00% 0/264 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.38% 1/265 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/264 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.38% 1/265 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Gastrointestinal disorders Intestinal haemorrhage	0.00% 0/264 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.38% 1/265 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/264 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.38% 1/265 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/264 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.38% 1/265 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Cardiac disorders Angina pectoris	0.38% 1/264 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.38% 1/265 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Cardiac disorders Atrial fibrillation	0.38% 1/264 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.38% 1/265 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Cardiac disorders Atrial flutter	0.38% 1/264 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.38% 1/265 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Cardiac disorders Coronary artery disease	0.38% 1/264 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.00% 0/265 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Cardiac disorders Acute myocardial infarction	0.00% 0/264 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.75% 2/265 • Number of events 2 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Cardiac disorders Coronary artery occlusion	0.00% 0/264 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.38% 1/265 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Cardiac disorders Sudden cardiac death	0.00% 0/264 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.38% 1/265 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
General disorders Non-cardiac chest pain	1.5% 4/264 • Number of events 4 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.00% 0/265 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
General disorders Chest Pain	0.00% 0/264 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.38% 1/265 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
General disorders Infusion site extravasation	0.38% 1/264 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.00% 0/265 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Infections and infestations Osteomyelitis	0.38% 1/264 • Number of events 2 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.00% 0/265 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Infections and infestations Wound infection	0.38% 1/264 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.00% 0/265 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Infections and infestations Chest wall abscess	0.00% 0/264 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.38% 1/265 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Infections and infestations Pneumonia	0.00% 0/264 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.38% 1/265 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Infections and infestations Sepsis syndrome	0.00% 0/264 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.38% 1/265 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Infections and infestations Urinary tract infection	0.00% 0/264 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.38% 1/265 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.38% 1/264 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.00% 0/265 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.38% 1/264 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.00% 0/265 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-small cell lung cancer	0.00% 0/264 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.38% 1/265 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.38% 1/264 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.00% 0/265 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	0.38% 1/264 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.00% 0/265 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/264 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.38% 1/265 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Hepatobiliary disorders Cholecystitis	0.38% 1/264 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.00% 0/265 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Hepatobiliary disorders Cholelithiasis	0.00% 0/264 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.38% 1/265 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Injury, poisoning and procedural complications Humerus fracture	0.38% 1/264 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.00% 0/265 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/264 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.38% 1/265 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/264 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.38% 1/265 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Injury, poisoning and procedural complications Joint dislocation	0.00% 0/264 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.38% 1/265 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Renal and urinary disorders Azotaemia	0.38% 1/264 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.00% 0/265 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Renal and urinary disorders Renal impairment	0.00% 0/264 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.38% 1/265 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Vascular disorders Deep vein thrombosis	0.38% 1/264 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.38% 1/265 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Vascular disorders Aortic aneurysm	0.00% 0/264 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.38% 1/265 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/264 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.38% 1/265 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Musculoskeletal and connective tissue disorders Myofascial pain syndrome	0.00% 0/264 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.38% 1/265 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Nervous system disorders Transient ischaemic attack	0.00% 0/264 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.38% 1/265 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.

Measure	PA32540 n=264 participants at risk PA32540 tablets contain 325 mg enteric coated (EC) aspirin and 40 mg immediate-release omeprazole dosed once daily (QD)	EC Aspirin n=265 participants at risk EC Aspirin 325 mg enteric coated tablet (PA32540 minus omeprazole) dosed once daily (QD)
Gastrointestinal disorders Gastritis	17.4% 46/264 • Number of events 51 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	16.6% 44/265 • Number of events 48 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Gastrointestinal disorders Dyspepsia	13.3% 35/264 • Number of events 40 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	34.0% 90/265 • Number of events 114 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Gastrointestinal disorders Gastritis erosive	10.2% 27/264 • Number of events 29 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	30.9% 82/265 • Number of events 97 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Gastrointestinal disorders Hiatus hernia	10.2% 27/264 • Number of events 27 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	9.8% 26/265 • Number of events 26 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Gastrointestinal disorders Duodenitis	5.7% 15/264 • Number of events 17 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	17.4% 46/265 • Number of events 47 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Gastrointestinal disorders Diarrhoea	3.4% 9/264 • Number of events 9 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	3.0% 8/265 • Number of events 8 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Gastrointestinal disorders Nausea	3.0% 8/264 • Number of events 8 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	2.6% 7/265 • Number of events 7 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Gastrointestinal disorders Oesophagitis	3.0% 8/264 • Number of events 8 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	11.7% 31/265 • Number of events 34 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Gastrointestinal disorders Gastrooesophageal reflux disease	2.7% 7/264 • Number of events 7 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	5.3% 14/265 • Number of events 15 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Gastrointestinal disorders Oesophageal disorder	2.7% 7/264 • Number of events 8 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	0.75% 2/265 • Number of events 2 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Gastrointestinal disorders Reflux oesophagitis	1.5% 4/264 • Number of events 4 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	2.6% 7/265 • Number of events 7 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Gastrointestinal disorders Erosive duodenitis	0.76% 2/264 • Number of events 2 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	9.4% 25/265 • Number of events 26 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Gastrointestinal disorders Duodenal ulcer	0.38% 1/264 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	3.4% 9/265 • Number of events 9 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Gastrointestinal disorders Erosive oesophagitis	0.38% 1/264 • Number of events 1 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	5.7% 15/265 • Number of events 15 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Infections and infestations Upper respiratory tract infection	1.9% 5/264 • Number of events 5 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	3.8% 10/265 • Number of events 10 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Infections and infestations Nasopharyngitis	1.5% 4/264 • Number of events 5 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	2.3% 6/265 • Number of events 6 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Infections and infestations Bronchitis	1.1% 3/264 • Number of events 3 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	3.4% 9/265 • Number of events 9 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Musculoskeletal and connective tissue disorders Arthralgia	0.76% 2/264 • Number of events 2 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	2.3% 6/265 • Number of events 9 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Nervous system disorders Dizziness	1.5% 4/264 • Number of events 4 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	2.3% 6/265 • Number of events 6 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.
Skin and subcutaneous tissue disorders Petechiae	1.1% 3/264 • Number of events 3 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.	3.8% 10/265 • Number of events 13 • Informed consent through 6 months plus 28 days for Serious Adverse Events and Randomization through 6 months for all non-serious adverse events.