Trial Outcomes & Findings for Study of Esomeprazole 20 mg or 40 mg vs Placebo Effectiveness on the Occurrence of Peptic Ulcers in Subjects on Low Dose Acetylsalicylic Acid (LDA) (NCT NCT00441727)

NCT ID: NCT00441727

Last Updated: 2012-07-16

Results Overview

The occurrence of ulcer (mucosal break measuring \>= 3 mm over its largest diameter with a sharply demarcated margin) was determined by endoscopy performed at baseline, 8 weeks and 26 weeks or upon withdrawal.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 2426 participants
• Primary outcome timeframe: During 26 weeks
• Results posted on: 2012-07-16

Participant Flow

The first subject was randomized 22 February 2007 and last subject completed 28 August 2008. Cardiologists, primary care physicians and gastroenterologists were the primary target investigators.

Participant milestones

Measure	Esomeprazole 40 Esomeprazole 40 mg every day for 26 weeks in subjects on continuous low-dose ASA (acetylsalicyclic acid) (75-325 mg)	Esomeproazole 20 Esomeprazole 20 mg every day for 26 weeks in subjects on continuous low dose ASA (75-325 mg)	Placebo Placebo every day for 26 weeks in subjects on continuous low-dose ASA (75-325 mg)
Overall Study STARTED	817	804	805
Overall Study COMPLETED	711	686	637
Overall Study NOT COMPLETED	106	118	168

Reasons for withdrawal

Measure	Esomeprazole 40 Esomeprazole 40 mg every day for 26 weeks in subjects on continuous low-dose ASA (acetylsalicyclic acid) (75-325 mg)	Esomeproazole 20 Esomeprazole 20 mg every day for 26 weeks in subjects on continuous low dose ASA (75-325 mg)	Placebo Placebo every day for 26 weeks in subjects on continuous low-dose ASA (75-325 mg)
Overall Study Protocol Violation	19	28	32
Overall Study Adverse Event	26	33	28
Overall Study Lack of Efficacy	7	8	48
Overall Study Withdrawal by Subject	40	34	47
Overall Study Lost to Follow-up	5	6	5
Overall Study Safety Reasons	3	1	3
Overall Study Various reason specified	6	8	5

Baseline Characteristics

Study of Esomeprazole 20 mg or 40 mg vs Placebo Effectiveness on the Occurrence of Peptic Ulcers in Subjects on Low Dose Acetylsalicylic Acid (LDA)

Baseline characteristics by cohort

Measure	Esomeprazole 40 n=817 Participants Esomeprazole 40 mg every day for 26 weeks in subjects on continuous low-dose ASA (acetylsalicyclic acid) (75-325 mg)	Esomeproazole 20 n=804 Participants Esomeprazole 20 mg every day for 26 weeks in subjects on continuous low dose ASA (75-325 mg)	Placebo n=805 Participants Placebo every day for 26 weeks in subjects on continuous low-dose ASA (75-325 mg)	Total n=2426 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	240 Participants n=5 Participants	246 Participants n=7 Participants	260 Participants n=5 Participants	746 Participants n=4 Participants
Age, Categorical >=65 years	577 Participants n=5 Participants	558 Participants n=7 Participants	545 Participants n=5 Participants	1680 Participants n=4 Participants
Sex: Female, Male Female	380 Participants n=5 Participants	375 Participants n=7 Participants	402 Participants n=5 Participants	1157 Participants n=4 Participants
Sex: Female, Male Male	437 Participants n=5 Participants	429 Participants n=7 Participants	403 Participants n=5 Participants	1269 Participants n=4 Participants

PRIMARY outcome

Timeframe: During 26 weeks

The occurrence of ulcer (mucosal break measuring >= 3 mm over its largest diameter with a sharply demarcated margin) was determined by endoscopy performed at baseline, 8 weeks and 26 weeks or upon withdrawal.

Outcome measures

Measure	Esomeprazole 40 n=817 Participants Esomeprazole 40 mg every day for 26 weeks in subjects on continuous low-dose ASA (acetylsalicyclic acid) (75-325 mg)	Esomeproazole 20 n=804 Participants Esomeprazole 20 mg every day for 26 weeks in subjects on continuous low dose ASA (75-325 mg)	Placebo n=805 Participants Placebo every day for 26 weeks in subjects on continuous low-dose ASA (75-325 mg)
Percentage of Participants Who Experienced the Occurence of Peptic Ulcer(s).	1.35 percentage of participants	1 percentage of participants	6.58 percentage of participants

SECONDARY outcome

Timeframe: During 26 weeks

The occurrence of gastric ulcer (mucosal break measuring >= 3 mm over its largest diameter with a sharply demarcated margin) was determined by endoscopy performed at baseline, 8 weeks and 26 weeks or upon withdrawal.

Outcome measures

Measure	Esomeprazole 40 n=817 Participants Esomeprazole 40 mg every day for 26 weeks in subjects on continuous low-dose ASA (acetylsalicyclic acid) (75-325 mg)	Esomeproazole 20 n=804 Participants Esomeprazole 20 mg every day for 26 weeks in subjects on continuous low dose ASA (75-325 mg)	Placebo n=805 Participants Placebo every day for 26 weeks in subjects on continuous low-dose ASA (75-325 mg)
Percentage of Participants Who Experienced the Occurence of Gastric Ulcer.	1.1 percentage of participants	0.75 percentage of participants	4.1 percentage of participants

SECONDARY outcome

Timeframe: During 26 weeks

The occurrence of duodenal ulcer (mucosal break measuring >= 3 mm over its largest diameter with a sharply demarcated margin) was determined by endoscopy performed at baseline, 8 weeks and 26 weeks or upon withdrawal.

Outcome measures

Measure	Esomeprazole 40 n=817 Participants Esomeprazole 40 mg every day for 26 weeks in subjects on continuous low-dose ASA (acetylsalicyclic acid) (75-325 mg)	Esomeproazole 20 n=804 Participants Esomeprazole 20 mg every day for 26 weeks in subjects on continuous low dose ASA (75-325 mg)	Placebo n=805 Participants Placebo every day for 26 weeks in subjects on continuous low-dose ASA (75-325 mg)
Percentage of Participants Who Experienced the Occurrence of Duodenal Ulcer.	0.24 percentage of participants	0.25 percentage of participants	2.73 percentage of participants

SECONDARY outcome

Timeframe: RDQ was assessed at baseline, 8 weeks, 16 week, 26 weeks or upon withdrawal.

Population: Patients randomized who took at least one dose of study drug and completed RDQ questionnaire at baseline and at week 26 or the week prior to last visit were analyzed.

RDQ contains 12 items on a 6-point Likert scale. Six items concern the frequence ('Did not have' to 'Daily') and six items concern the severity ('Did not have' to 'Severe'). The dyspepsia dimension contains the items 'Burning feeling in the center of the upper stomach' and 'Pain in the center of the upper stomach'. Best score possible 0, worst score possible - daily occurrence.

Outcome measures

Measure	Esomeprazole 40 n=782 Participants Esomeprazole 40 mg every day for 26 weeks in subjects on continuous low-dose ASA (acetylsalicyclic acid) (75-325 mg)	Esomeproazole 20 n=758 Participants Esomeprazole 20 mg every day for 26 weeks in subjects on continuous low dose ASA (75-325 mg)	Placebo n=763 Participants Placebo every day for 26 weeks in subjects on continuous low-dose ASA (75-325 mg)
Number of Participants Reporting 0 in the Dichotomized RDQ (Reflux and Disease Questionnaire) Score (0 Versus >0) for the Dyspepsia Dimension During the 26-week Visit or the Week Prior to the Last Visit.	591 participants	577 participants	504 participants

SECONDARY outcome

Timeframe: RDQ was assessed at baseline, 8 weeks, 16 week, 26 weeks or upon withdrawal.

Population: Patients randomized who took at least one dose of study drug and completed RDQ questionnaire at baseline and at week 26 or the week prior to last visit were analyzed.

RDQ contains 12 items on a 6-point Likert scale. Six items concern the frequency ('Did not have' to 'Daily') and six items concern the severity ('Did not have' to 'Severe'). Gastroesophageal reflux disease (GERD) items: 'Acid taste in the mouth', 'Unpleasant movement of materials upward from the stomach', 'Burning feeling behind the breastbone' and 'Pain behind the breastbone'. Best score possible 0, worst score possible - daily occurrence.

Outcome measures

Measure	Esomeprazole 40 n=782 Participants Esomeprazole 40 mg every day for 26 weeks in subjects on continuous low-dose ASA (acetylsalicyclic acid) (75-325 mg)	Esomeproazole 20 n=758 Participants Esomeprazole 20 mg every day for 26 weeks in subjects on continuous low dose ASA (75-325 mg)	Placebo n=763 Participants Placebo every day for 26 weeks in subjects on continuous low-dose ASA (75-325 mg)
Number of Participants Reporting 0 in the Dichotomized RDQ (Reflux and Disease Questionnaire) Score (0 Versus >0) for the Gastroesophageal Reflux Disease Dimension During the 26-week Visit or the Week Prior to the Last Visit.	554 participants	537 participants	451 participants

SECONDARY outcome

Timeframe: The number of erosions was determined by endoscopy performed at baseline, 8 weeks and 26 weeks or upon withdrawal.

Population: Patients randomized who had endoscopy performed at baseline, 8 weeks and 26 weeks or upon withdrawal.

Outcome measures

Measure	Esomeprazole 40 n=772 Participants Esomeprazole 40 mg every day for 26 weeks in subjects on continuous low-dose ASA (acetylsalicyclic acid) (75-325 mg)	Esomeproazole 20 n=753 Participants Esomeprazole 20 mg every day for 26 weeks in subjects on continuous low dose ASA (75-325 mg)	Placebo n=748 Participants Placebo every day for 26 weeks in subjects on continuous low-dose ASA (75-325 mg)
Number of Participants With Gastric and/or Duodenal Erosions.	214 participants	213 participants	380 participants

Adverse Events

Esomeprazole 40

Serious events: 46 serious events

Other events: 32 other events

Deaths: 0 deaths

Esomeproazole 20

Serious events: 40 serious events

Other events: 42 other events

Deaths: 0 deaths

Placebo

Serious events: 35 serious events

Other events: 31 other events

Deaths: 0 deaths

Serious adverse events

Measure	Esomeprazole 40 Esomeprazole 40 mg every day for 26 weeks in subjects on continuous low-dose ASA (acetylsalicyclic acid) (75-325 mg)	Esomeproazole 20 Esomeprazole 20 mg every day for 26 weeks in subjects on continuous low dose ASA (75-325 mg)	Placebo Placebo every day for 26 weeks in subjects on continuous low-dose ASA (75-325 mg)
Vascular disorders Hypertensive Crisis	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.12% 1/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Vascular disorders Thromboangiitis Obliterans	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.12% 1/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Vascular disorders Varicose Vein	0.12% 1/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Cardiac disorders Acute Coronary Syndrome	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.13% 1/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Cardiac disorders Angina Pectoris	0.25% 2/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.12% 1/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Cardiac disorders Angina Unstable	0.25% 2/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Cardiac disorders Atrial Fibrillation	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.13% 1/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.12% 1/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Cardiac disorders Cardiac Arrest	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.25% 2/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.12% 1/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Cardiac disorders Cardiac Failure	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.13% 1/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.12% 1/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Cardiac disorders Cardiac Failure Congestive	0.12% 1/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Cardiac disorders Coronary Artery Disease	0.25% 2/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.13% 1/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.12% 1/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Cardiac disorders Coronary Artery Stenosis	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.12% 1/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Cardiac disorders Myocardial Infarction	0.12% 1/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.13% 1/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Cardiac disorders Myocardial Ischaemia	0.12% 1/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Ear and labyrinth disorders Vertigo	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.13% 1/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Endocrine disorders Acromegaly	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.12% 1/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Gastrointestinal disorders Abdominal Pain	0.12% 1/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Gastrointestinal disorders Abdominal Pain Upper	0.12% 1/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Gastrointestinal disorders Colitis	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.13% 1/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Gastrointestinal disorders Diarrhoea	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.13% 1/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Gastrointestinal disorders Diverticulum	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.12% 1/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Gastrointestinal disorders Duodenal Perforation	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.13% 1/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Gastrointestinal disorders Dyspepsia	0.12% 1/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Gastrointestinal disorders Gastric Ulcer	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.12% 1/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Gastrointestinal disorders Gastritis	0.12% 1/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Gastrointestinal disorders Inguinal Hernia	0.25% 2/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.12% 1/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Gastrointestinal disorders Intestinal Ischaemia	0.12% 1/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Gastrointestinal disorders Intestinal Obstruction	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.13% 1/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Gastrointestinal disorders Irritable Bowel Syndrome	0.12% 1/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.13% 1/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Gastrointestinal disorders Pancreatitis	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.13% 1/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Gastrointestinal disorders Pancreatitis Acute	0.25% 2/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.13% 1/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Gastrointestinal disorders Subileus	0.12% 1/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Gastrointestinal disorders Vomiting	0.12% 1/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.13% 1/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
General disorders Chest Pain	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.13% 1/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
General disorders Death	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.13% 1/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
General disorders Non-Cardiac Chest Pain	0.12% 1/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.12% 1/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
General disorders Sudden Death	0.12% 1/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Hepatobiliary disorders Cholecystitis	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.12% 1/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Hepatobiliary disorders Cholecystitis Acute	0.12% 1/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.13% 1/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Hepatobiliary disorders Cholelithiasis	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.13% 1/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Hepatobiliary disorders Hepatitis Toxic	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.13% 1/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Infections and infestations Bronchitis	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.13% 1/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Infections and infestations Diverticulitis	0.12% 1/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Infections and infestations Erysipelas	0.12% 1/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Infections and infestations Lobar Pneumonia	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.13% 1/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Infections and infestations Meningitis	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.12% 1/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Infections and infestations Pyelonephritis	0.12% 1/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Infections and infestations Pyelonephritis Acute	0.12% 1/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Infections and infestations Sepsis	0.12% 1/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Infections and infestations Urinary Tract Infection	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.12% 1/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Injury, poisoning and procedural complications Arthropod Bite	0.12% 1/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Injury, poisoning and procedural complications Dislocation Of Joint Prosthesis	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.12% 1/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Injury, poisoning and procedural complications Femur Fracture	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.12% 1/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Injury, poisoning and procedural complications Hand Fracture	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.12% 1/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Injury, poisoning and procedural complications Humerus Fracture	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.12% 1/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Injury, poisoning and procedural complications Joint Dislocation	0.12% 1/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Injury, poisoning and procedural complications Upper Limb Fracture	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.12% 1/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Injury, poisoning and procedural complications Vascular Graft Occlusion	0.12% 1/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Injury, poisoning and procedural complications Wrist Fracture	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.12% 1/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Metabolism and nutrition disorders Diabetes Mellitus	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.13% 1/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Metabolism and nutrition disorders Gout	0.12% 1/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.13% 1/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.13% 1/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.13% 1/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.12% 1/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Musculoskeletal and connective tissue disorders Back Pain	0.12% 1/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Musculoskeletal and connective tissue disorders Flank Pain	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.12% 1/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.12% 1/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Musculoskeletal and connective tissue disorders Pain In Extremity	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.12% 1/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma	0.12% 1/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.12% 1/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma Pancreas	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.12% 1/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bile Duct Cancer	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.12% 1/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric Cancer	0.12% 1/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.12% 1/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastrointestinal Tract Adenoma	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.12% 1/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lentigo Maligna Stage Unspecified	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.13% 1/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung Neoplasm Malignant	0.12% 1/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.13% 1/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal Adenocarcinoma	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.13% 1/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.12% 1/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal Carcinoma	0.12% 1/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate Cancer	0.12% 1/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal Cancer	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.12% 1/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal Cell Carcinoma	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.13% 1/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Signet-Ring Cell Carcinoma	0.12% 1/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid Cancer	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.13% 1/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Transitional Cell Carcinoma	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.12% 1/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Nervous system disorders Carotid Arteriosclerosis	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.12% 1/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Nervous system disorders Cerebral Circulatory Failure	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.13% 1/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Nervous system disorders Cerebral Infarction	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.13% 1/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Nervous system disorders Cerebrovascular Accident	0.12% 1/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.25% 2/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Nervous system disorders Dizziness	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.12% 1/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Nervous system disorders Syncope	0.12% 1/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.13% 1/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Nervous system disorders Transient Ischaemic Attack	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.25% 2/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Renal and urinary disorders Nephrolithiasis	0.12% 1/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Renal and urinary disorders Renal Failure Acute	0.12% 1/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Renal and urinary disorders Benign Prostatic Hyperplasia	0.12% 1/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Respiratory, thoracic and mediastinal disorders Asthma	0.12% 1/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.13% 1/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.13% 1/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Respiratory, thoracic and mediastinal disorders Pulmonary Sarcoidosis	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.13% 1/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Skin and subcutaneous tissue disorders Skin Ulcer	0.00% 0/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.13% 1/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Vascular disorders Deep Vein Thrombosis	0.12% 1/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	0.00% 0/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.

Other adverse events

Measure	Esomeprazole 40 Esomeprazole 40 mg every day for 26 weeks in subjects on continuous low-dose ASA (acetylsalicyclic acid) (75-325 mg)	Esomeproazole 20 Esomeprazole 20 mg every day for 26 weeks in subjects on continuous low dose ASA (75-325 mg)	Placebo Placebo every day for 26 weeks in subjects on continuous low-dose ASA (75-325 mg)
Gastrointestinal disorders Diarrhoea	2.6% 21/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	3.3% 26/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	2.2% 18/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.
Respiratory, thoracic and mediastinal disorders Bronchitis	1.4% 11/814 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	2.0% 16/799 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.	1.6% 13/801 Nine (9) randomized subjects were not evaluable for safety analysis because they were never exposed to investigational product. Three (3) additional subjects were excluded from safety. They were exposed to investigational product, but did not have any post-dose data.

Additional Information

Gerard Lynch

AstraZeneca

Email: AZTrial_Results_Posting@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: OTHER