Trial Outcomes & Findings for High Dose Esomeprazole Na for Prevention of Rebleeding After Successful Endoscopic Therapy of a Bleeding Peptic Ulcer (NCT NCT01757275)

NCT ID: NCT01757275

Last Updated: 2016-03-08

Results Overview

Diagnostic criteria for clinically significant rebleeding based on either A, B or C: A) Endoscopy - initiated by clinical signs of bleeding defined as one of B1 or B2 or B3 and endoscopic verification, ie one of A1 or A2. A1: Blood in stomach (this criteria cannot be used during the first 6 hours after primary endoscopic haemostasis). A2: A verified active bleeding from a peptic ulcer (Forrest Ia, Ib). B) A true clinically based definition, at least two of B1 and/or B2 and/or B3. B1: Vomiting of fresh blood or fresh blood in a gastric tube or haematochezia or melaena after a normal stool. B2: Decrease in Hb \>20g/L (or Hct \>6%) during 24 hours or an increase in Hb \<10g/L (or Hct \<3%) despite ≥2 units of blood has been transfused during 24hours. B3: Unstable circulation systolic blood pressure ≤ 90 mmHg or pulse ≥110/min (after have had a stable circulation). C) Haematemesis. Vomiting significant amounts (\>200 ml) of fresh blood as estimated by the investigator.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 239 participants
• Primary outcome timeframe: 72 hours
• Results posted on: 2016-03-08

Participant Flow

Overall, 239 patients were enrolled from 19 centres in China. The first patient entered the study on 26 February 2013 and the last patient completed the study on 30 December 2014. Of the 239 patients enrolled into the study, 222 (92.9%) patients were randomised to treatment.

17 patients were not assigned to treatment, 15 patients did not fulfil the eligibility criteria, 1 was due to patient decision, and 1 patient due to "other" (not enough experimental drug).

Participant milestones

Measure	Esomeprazole Esomeprazole iv 80 mg bolus infusion for 30 min followed by Esomeprazole iv 8 mg/hour for 71.5 hours and esomeprazole oral 40 mg once daily for 27 days	Cimetidine Cimetidine iv 200 mg bolus infusion for 30 min followed by Cimetidine iv 60 mg/hour for 71.5 hours and esomeprazole oral 40 mg once daily for 27 days
Overall Study STARTED	111	111
Overall Study COMPLETED	102	98
Overall Study NOT COMPLETED	9	13

Reasons for withdrawal

Measure	Esomeprazole Esomeprazole iv 80 mg bolus infusion for 30 min followed by Esomeprazole iv 8 mg/hour for 71.5 hours and esomeprazole oral 40 mg once daily for 27 days	Cimetidine Cimetidine iv 200 mg bolus infusion for 30 min followed by Cimetidine iv 60 mg/hour for 71.5 hours and esomeprazole oral 40 mg once daily for 27 days
Overall Study Lost to Follow-up	1	2
Overall Study Adverse Event	3	3
Overall Study Withdrawal by Subject	2	4
Overall Study Not treated	3	4

Baseline Characteristics

High Dose Esomeprazole Na for Prevention of Rebleeding After Successful Endoscopic Therapy of a Bleeding Peptic Ulcer

Baseline characteristics by cohort

Measure	Esomeprazole n=108 Participants Esomeprazole iv 80 mg bolus infusion for 30 min followed by Esomeprazole iv 8 mg/hour for 71.5 hours and esomeprazole oral 40 mg once daily for 27 days	Cimetidine n=107 Participants Cimetidine iv 200 mg bolus infusion for 30 min followed by Cimetidine iv 60 mg/hour for 71.5 hours and esomeprazole oral 40 mg once daily for 27 days	Total n=215 Participants Total of all reporting groups
Age, Continuous Age	42.4 years STANDARD_DEVIATION 12.79 • n=5 Participants	41.8 years STANDARD_DEVIATION 12.96 • n=7 Participants	42.1 years STANDARD_DEVIATION 12.85 • n=5 Participants
Age, Customized <=65 years	104 participants n=5 Participants	103 participants n=7 Participants	207 participants n=5 Participants
Age, Customized >65 years	4 participants n=5 Participants	4 participants n=7 Participants	8 participants n=5 Participants
Sex: Female, Male Female	25 Participants n=5 Participants	24 Participants n=7 Participants	49 Participants n=5 Participants
Sex: Female, Male Male	83 Participants n=5 Participants	83 Participants n=7 Participants	166 Participants n=5 Participants
Race/Ethnicity, Customized Asian/Chinese	108 participants n=5 Participants	107 participants n=7 Participants	215 participants n=5 Participants
Number of patients with one bleeding ulcer	108 participants n=5 Participants	107 participants n=7 Participants	215 participants n=5 Participants
Forrest class Ia	5 participants n=5 Participants	4 participants n=7 Participants	9 participants n=5 Participants
Forrest class Ib	58 participants n=5 Participants	64 participants n=7 Participants	122 participants n=5 Participants
Forrest class IIa	33 participants n=5 Participants	24 participants n=7 Participants	57 participants n=5 Participants
Forrest class IIb	12 participants n=5 Participants	15 participants n=7 Participants	27 participants n=5 Participants
Bleeding ulcer size	8.2 mm STANDARD_DEVIATION 4.8 • n=5 Participants	8.1 mm STANDARD_DEVIATION 3.6 • n=7 Participants	8.1 mm STANDARD_DEVIATION 4.3 • n=5 Participants
Ulcer location Stomach	17 participants n=5 Participants	8 participants n=7 Participants	25 participants n=5 Participants
Ulcer location Duodenum	84 participants n=5 Participants	89 participants n=7 Participants	173 participants n=5 Participants
Ulcer location Stomach and Duodenum	7 participants n=5 Participants	10 participants n=7 Participants	17 participants n=5 Participants
Number of patients with ulcers of different sizes <=2 cm	105 participants n=5 Participants	106 participants n=7 Participants	211 participants n=5 Participants
Number of patients with ulcers of different sizes >2 cm	3 participants n=5 Participants	1 participants n=7 Participants	4 participants n=5 Participants
Number of patients with single and multiple ulcers Single	89 participants n=5 Participants	89 participants n=7 Participants	178 participants n=5 Participants
Number of patients with single and multiple ulcers Multiple	19 participants n=5 Participants	18 participants n=7 Participants	37 participants n=5 Participants

PRIMARY outcome

Timeframe: 72 hours

Population: Full analysis set (FAS). All randomised patients, who started the randomised iv treatment (bolus dose), were included in the FAS.

Diagnostic criteria for clinically significant rebleeding based on either A, B or C:

A) Endoscopy - initiated by clinical signs of bleeding defined as one of B1 or B2 or B3 and endoscopic verification, ie one of A1 or A2.

A1: Blood in stomach (this criteria cannot be used during the first 6 hours after primary endoscopic haemostasis). A2: A verified active bleeding from a peptic ulcer (Forrest Ia, Ib).

B) A true clinically based definition, at least two of B1 and/or B2 and/or B3. B1: Vomiting of fresh blood or fresh blood in a gastric tube or haematochezia or melaena after a normal stool. B2: Decrease in Hb >20g/L (or Hct >6%) during 24 hours or an increase in Hb <10g/L (or Hct <3%) despite ≥2 units of blood has been transfused during 24hours. B3: Unstable circulation systolic blood pressure ≤ 90 mmHg or pulse ≥110/min (after have had a stable circulation).

C) Haematemesis. Vomiting significant amounts (>200 ml) of fresh blood as estimated by the investigator.

Outcome measures

Measure	Esomeprazole n=108 Participants Esomeprazole iv 80 mg bolus infusion for 30 min followed by Esomeprazole iv 8 mg/hour for 71.5 hours and esomeprazole oral 40 mg once daily for 27 days	Cimetidine n=107 Participants Cimetidine iv 200 mg bolus infusion for 30 min followed by Cimetidine iv 60 mg/hour for 71.5 hours and esomeprazole oral 40 mg once daily for 27 days
Rate of Clinically Significant Rebleeding Within 72 Hours Rebleeding	1 participants	6 participants
Rate of Clinically Significant Rebleeding Within 72 Hours No rebleeding	107 participants	101 participants

SECONDARY outcome

Timeframe: 7 days

Population: FAS

Diagnostic criteria for clinically significant rebleeding based on either A, B or C:

A) Endoscopy - initiated by clinical signs of bleeding defined as one of B1 or B2 or B3 and endoscopic verification, ie one of A1 or A2.

A1: Blood in stomach (this criteria cannot be used during the first 6 hours after primary endoscopic haemostasis). A2: A verified active bleeding from a peptic ulcer (Forrest Ia, Ib).

B) A true clinically based definition, at least two of B1 and/or B2 and/or B3. B1: Vomiting of fresh blood or fresh blood in a gastric tube or haematochezia or melaena after a normal stool. B2: Decrease in Hb >20g/L (or Hct >6%) during 24 hours or an increase in Hb <10g/L (or Hct <3%) despite ≥2 units of blood has been transfused during 24hours. B3: Unstable circulation systolic blood pressure ≤ 90 mmHg or pulse ≥110/min (after have had a stable circulation).

C) Haematemesis. Vomiting significant amounts (>200 ml) of fresh blood as estimated by the investigator.

Outcome measures

Measure	Esomeprazole n=108 Participants Esomeprazole iv 80 mg bolus infusion for 30 min followed by Esomeprazole iv 8 mg/hour for 71.5 hours and esomeprazole oral 40 mg once daily for 27 days	Cimetidine n=107 Participants Cimetidine iv 200 mg bolus infusion for 30 min followed by Cimetidine iv 60 mg/hour for 71.5 hours and esomeprazole oral 40 mg once daily for 27 days
Rate of Clinically Significant Rebleeding During 7 Days No rebleeding	105 participants	101 participants
Rate of Clinically Significant Rebleeding During 7 Days Rebleeding	3 participants	6 participants

SECONDARY outcome

Timeframe: 30 days

Population: FAS

Diagnostic criteria for clinically significant rebleeding based on either A, B or C:

A) Endoscopy - initiated by clinical signs of bleeding defined as one of B1 or B2 or B3 and endoscopic verification, ie one of A1 or A2.

A1: Blood in stomach (this criteria cannot be used during the first 6 hours after primary endoscopic haemostasis). A2: A verified active bleeding from a peptic ulcer (Forrest Ia, Ib).

B) A true clinically based definition, at least two of B1 and/or B2 and/or B3. B1: Vomiting of fresh blood or fresh blood in a gastric tube or haematochezia or melaena after a normal stool. B2: Decrease in Hb >20g/L (or Hct >6%) during 24 hours or an increase in Hb <10g/L (or Hct <3%) despite ≥2 units of blood has been transfused during 24hours. B3: Unstable circulation systolic blood pressure ≤ 90 mmHg or pulse ≥110/min (after have had a stable circulation).

C) Haematemesis. Vomiting significant amounts (>200 ml) of fresh blood as estimated by the investigator.

Outcome measures

Measure	Esomeprazole n=108 Participants Esomeprazole iv 80 mg bolus infusion for 30 min followed by Esomeprazole iv 8 mg/hour for 71.5 hours and esomeprazole oral 40 mg once daily for 27 days	Cimetidine n=107 Participants Cimetidine iv 200 mg bolus infusion for 30 min followed by Cimetidine iv 60 mg/hour for 71.5 hours and esomeprazole oral 40 mg once daily for 27 days
Rate of Clinically Significant Rebleeding During 30 Days Rebleeding	3 participants	6 participants
Rate of Clinically Significant Rebleeding During 30 Days No rebleeding	105 participants	101 participants

SECONDARY outcome

Timeframe: 72 hours

Population: FAS

Outcome measures

Measure	Esomeprazole n=108 Participants Esomeprazole iv 80 mg bolus infusion for 30 min followed by Esomeprazole iv 8 mg/hour for 71.5 hours and esomeprazole oral 40 mg once daily for 27 days	Cimetidine n=107 Participants Cimetidine iv 200 mg bolus infusion for 30 min followed by Cimetidine iv 60 mg/hour for 71.5 hours and esomeprazole oral 40 mg once daily for 27 days
Number of Patients With Endoscopic Re-treatment Within 72 Hours No re-treatment	108 participants	106 participants
Number of Patients With Endoscopic Re-treatment Within 72 Hours Re-treatment	0 participants	1 participants

SECONDARY outcome

Timeframe: 30 days

Population: FAS

Outcome measures

Measure	Esomeprazole n=108 Participants Esomeprazole iv 80 mg bolus infusion for 30 min followed by Esomeprazole iv 8 mg/hour for 71.5 hours and esomeprazole oral 40 mg once daily for 27 days	Cimetidine n=107 Participants Cimetidine iv 200 mg bolus infusion for 30 min followed by Cimetidine iv 60 mg/hour for 71.5 hours and esomeprazole oral 40 mg once daily for 27 days
Number of Patients With Endoscopic Re-treatment Within 30 Days No re-treatment	106 participants	106 participants
Number of Patients With Endoscopic Re-treatment Within 30 Days Re-treatment	2 participants	1 participants

SECONDARY outcome

Timeframe: within 72 hours

Population: FAS

Outcome measures

Measure	Esomeprazole n=108 Participants Esomeprazole iv 80 mg bolus infusion for 30 min followed by Esomeprazole iv 8 mg/hour for 71.5 hours and esomeprazole oral 40 mg once daily for 27 days	Cimetidine n=107 Participants Cimetidine iv 200 mg bolus infusion for 30 min followed by Cimetidine iv 60 mg/hour for 71.5 hours and esomeprazole oral 40 mg once daily for 27 days
Number of Patients With Surgery Due to Rebleeding Within 72 Hours No surgery	108 participants	107 participants
Number of Patients With Surgery Due to Rebleeding Within 72 Hours Surgery	0 participants	0 participants

SECONDARY outcome

Timeframe: within 30 days

Population: FAS

Outcome measures

Measure	Esomeprazole n=108 Participants Esomeprazole iv 80 mg bolus infusion for 30 min followed by Esomeprazole iv 8 mg/hour for 71.5 hours and esomeprazole oral 40 mg once daily for 27 days	Cimetidine n=107 Participants Cimetidine iv 200 mg bolus infusion for 30 min followed by Cimetidine iv 60 mg/hour for 71.5 hours and esomeprazole oral 40 mg once daily for 27 days
Number of Patients With Surgery Due to Rebleeding Within 30 Days No surgery	108 participants	106 participants
Number of Patients With Surgery Due to Rebleeding Within 30 Days Surgery	0 participants	1 participants

SECONDARY outcome

Timeframe: within 72 hours

Population: FAS

Outcome measures

Measure	Esomeprazole n=108 Participants Esomeprazole iv 80 mg bolus infusion for 30 min followed by Esomeprazole iv 8 mg/hour for 71.5 hours and esomeprazole oral 40 mg once daily for 27 days	Cimetidine n=107 Participants Cimetidine iv 200 mg bolus infusion for 30 min followed by Cimetidine iv 60 mg/hour for 71.5 hours and esomeprazole oral 40 mg once daily for 27 days
Number of Blood Units Transfused Within 72 Hours	14 blood units	21 blood units

SECONDARY outcome

Timeframe: within 30 days

Population: FAS

Outcome measures

Measure	Esomeprazole n=108 Participants Esomeprazole iv 80 mg bolus infusion for 30 min followed by Esomeprazole iv 8 mg/hour for 71.5 hours and esomeprazole oral 40 mg once daily for 27 days	Cimetidine n=107 Participants Cimetidine iv 200 mg bolus infusion for 30 min followed by Cimetidine iv 60 mg/hour for 71.5 hours and esomeprazole oral 40 mg once daily for 27 days
Number of Blood Units Transfused Within 30 Days	18 blood units	21 blood units

Adverse Events

Esomeprazole

Serious events: 5 serious events

Other events: 22 other events

Deaths: 0 deaths

Cimetidine

Serious events: 5 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Measure	Esomeprazole n=110 participants at risk Esomeprazole iv 80 mg bolus infusion for 30 min followed by Esomeprazole iv 8 mg/hour for 71.5 hours and esomeprazole oral 40 mg once daily for 27 days	Cimetidine n=105 participants at risk Cimetidine iv 200 mg bolus infusion for 30 min followed by Cimetidine iv 60 mg/hour for 71.5 hours and esomeprazole oral 40 mg once daily for 27 days
Gastrointestinal disorders Duodenal ulcer haemorrhage	1.8% 2/110 • Number of events 2 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	1.9% 2/105 • Number of events 2 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Gastrointestinal disorders Gastric ulcer haemorrhage	0.91% 1/110 • Number of events 1 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.00% 0/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.95% 1/105 • Number of events 1 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Infections and infestations Bronchitis	0.00% 0/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.95% 1/105 • Number of events 1 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Investigations Blood fibrinogen decreased	0.91% 1/110 • Number of events 1 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.00% 0/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.91% 1/110 • Number of events 1 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.00% 0/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Psychiatric disorders Persecutory delusion	0.00% 0/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.95% 1/105 • Number of events 1 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Renal and urinary disorders Nephrolithiasis	0.00% 0/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.95% 1/105 • Number of events 1 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.

Other adverse events

Measure	Esomeprazole n=110 participants at risk Esomeprazole iv 80 mg bolus infusion for 30 min followed by Esomeprazole iv 8 mg/hour for 71.5 hours and esomeprazole oral 40 mg once daily for 27 days	Cimetidine n=105 participants at risk Cimetidine iv 200 mg bolus infusion for 30 min followed by Cimetidine iv 60 mg/hour for 71.5 hours and esomeprazole oral 40 mg once daily for 27 days
Infections and infestations Bronchitis	0.00% 0/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.95% 1/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Infections and infestations Nasopharyngitis	0.91% 1/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.00% 0/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Infections and infestations Upper respiratory tract infection	0.00% 0/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.95% 1/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.91% 1/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.00% 0/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Blood and lymphatic system disorders Anaemia	0.00% 0/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.95% 1/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Blood and lymphatic system disorders Haemorrhagic anaemia	0.00% 0/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.95% 1/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Metabolism and nutrition disorders Hypochloraemia	0.91% 1/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.00% 0/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Metabolism and nutrition disorders Hypokalaemia	0.91% 1/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.00% 0/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Metabolism and nutrition disorders Hyponatraemia	0.91% 1/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.00% 0/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Psychiatric disorders Agitation	0.91% 1/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.00% 0/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Psychiatric disorders Persecutory delusion	0.00% 0/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.95% 1/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Nervous system disorders Dizziness	0.91% 1/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.95% 1/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Nervous system disorders Headache	0.00% 0/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.95% 1/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Cardiac disorders Myocardial ischaemia	0.00% 0/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.95% 1/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Cardiac disorders Palpitations	0.00% 0/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.95% 1/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Respiratory, thoracic and mediastinal disorders Cough	1.8% 2/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.00% 0/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.95% 1/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Respiratory, thoracic and mediastinal disorders Pleurisy	0.00% 0/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.95% 1/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Gastrointestinal disorders Duodenal ulcer haemorrhage	1.8% 2/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	1.9% 2/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Gastrointestinal disorders Diarrhoea	1.8% 2/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.95% 1/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Gastrointestinal disorders Melaena	0.91% 1/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	1.9% 2/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Gastrointestinal disorders Constipation	0.91% 1/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.95% 1/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Gastrointestinal disorders Abdominal distension	0.91% 1/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.00% 0/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Gastrointestinal disorders Dry mouth	0.91% 1/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.00% 0/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Gastrointestinal disorders Dyspepsia	0.91% 1/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.00% 0/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Gastrointestinal disorders Gastric ulcer haemorrhage	0.91% 1/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.00% 0/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.95% 1/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Gastrointestinal disorders Gastrointestinal motility disorder	0.00% 0/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.95% 1/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Hepatobiliary disorders Cholelithiasis	0.00% 0/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.95% 1/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Hepatobiliary disorders Hepatic function abnormal	0.00% 0/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.95% 1/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Skin and subcutaneous tissue disorders Ecchymosis	0.00% 0/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.95% 1/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Skin and subcutaneous tissue disorders Erythema	0.91% 1/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.00% 0/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Skin and subcutaneous tissue disorders Rash	0.91% 1/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.00% 0/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.95% 1/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Musculoskeletal and connective tissue disorders Back pain	0.91% 1/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.00% 0/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Musculoskeletal and connective tissue disorders Gouty arthritis	0.91% 1/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.00% 0/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Renal and urinary disorders Nephrolithiasis	0.00% 0/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.95% 1/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Reproductive system and breast disorders Haematospermia	0.91% 1/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.00% 0/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
General disorders Pyrexia	1.8% 2/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	1.9% 2/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
General disorders Asthenia	0.00% 0/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.95% 1/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
General disorders Non-cardiac chest pain	0.00% 0/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.95% 1/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Investigations Blood fibrinogen decreased	0.91% 1/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.00% 0/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Investigations Haematocrit decreased	0.00% 0/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.95% 1/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Investigations Haemoglobin decreased	0.00% 0/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.95% 1/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Investigations Liver function test abnormal	0.91% 1/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.00% 0/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Investigations Neutrophil count increased	0.91% 1/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.00% 0/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Investigations Neutrophil percentage increased	0.91% 1/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.00% 0/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Investigations Red blood cell count decreased	0.00% 0/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.95% 1/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Investigations White blood cell count increased	0.91% 1/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.00% 0/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Injury, poisoning and procedural complications Laceration	0.00% 0/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.95% 1/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.
Injury, poisoning and procedural complications Ligament sprain	0.00% 0/110 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.	0.95% 1/105 • AEs will be collected from the time of the first administration of IP until the end of study, up to 35 days. SAEs will be collected from signed inform consent until the end of the study, up to 36 days.

Additional Information

Huifang Chen

AstraZeneca

Phone: +86 21 60301335

Email: ariel.chen@astrazeneca.com

Results disclosure agreements

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