Trial Outcomes & Findings for Bexagliflozin Efficacy and Safety Trial (NCT NCT02558296)

NCT ID: NCT02558296

Last Updated: 2021-07-14

Results Overview

The primary efficacy objective of this trial is to evaluate the placebo-adjusted change in HbA1c from baseline after 24 weeks of treatment with 20 mg bexagliflozin tablets in type 2 diabetic subjects with increased risk of cardiovascular adverse events.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 1700 participants
• Primary outcome timeframe: 24 weeks
• Results posted on: 2021-07-14

Participant Flow

A total of 1700 patients were recruited from 10 countries: Canada, Czech Republic, Demark, Republic of Korea, Mexico, the Netherlands, Poland, Russian Federation, Taiwan, and the United States.

Subjects ≥ 40 years old with inadequately controlled T2DM with HbA1c between 7.5% (7.0% since protocol version 8) and 11% on stable medications and elevated risk for CV adverse events were enrolled. All subjects must belong to 1 of 3 CV risk groups to be eligible. All eligible subjects took placebo during 13 ± 2 days run-in period.

Participant milestones

Measure	Bexagliflozin Tablets, 20 mg Each subject will receive bexagliflozin 20 mg once daily for the duration of the study. Bexagliflozin: 20 mg, tablet	Placebo Tablets Each subject will receive placebo (inactive tablet) once daily for the duration of the study. Placebo: 20 mg tablet to match active comparator
Completed the Study Through Week 24 STARTED	1133	567
Completed the Study Through Week 24 COMPLETED	1089	542
Completed the Study Through Week 24 NOT COMPLETED	44	25
Completed the Study STARTED	1133	567
Completed the Study COMPLETED	987	482
Completed the Study NOT COMPLETED	146	85

Reasons for withdrawal

Measure	Bexagliflozin Tablets, 20 mg Each subject will receive bexagliflozin 20 mg once daily for the duration of the study. Bexagliflozin: 20 mg, tablet	Placebo Tablets Each subject will receive placebo (inactive tablet) once daily for the duration of the study. Placebo: 20 mg tablet to match active comparator
Completed the Study Through Week 24 Adverse Event	9	3
Completed the Study Through Week 24 Death	7	7
Completed the Study Through Week 24 Lost to Follow-up	8	1
Completed the Study Through Week 24 Physician Decision	1	0
Completed the Study Through Week 24 Protocol Violation	1	1
Completed the Study Through Week 24 Withdrawal by Subject	17	13
Completed the Study Through Week 24 The subject was randomized, but did not take any investigational product	1	0
Completed the Study Adverse Event	14	5
Completed the Study Death	39	25
Completed the Study Lost to Follow-up	31	23
Completed the Study Physician Decision	6	0
Completed the Study Protocol Violation	2	1
Completed the Study Withdrawal by Subject	53	31
Completed the Study The subject was randomized, but did not take any investigational product	1	0

Baseline Characteristics

Bexagliflozin Efficacy and Safety Trial

Baseline characteristics by cohort

Measure	Bexagliflozin Tablets, 20 mg n=1133 Participants Each subject will receive bexagliflozin 20 mg once daily for the duration of the study. Bexagliflozin: 20 mg, tablet	Placebo Tablets n=567 Participants Each subject will receive placebo (inactive tablet) once daily for the duration of the study. Placebo: 20 mg tablet to match active comparator	Total n=1700 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
Age, Categorical Between 18 and 65 years	562 Participants n=5 Participants	276 Participants n=7 Participants	838 Participants n=5 Participants
Age, Categorical >=65 years	571 Participants n=5 Participants	291 Participants n=7 Participants	862 Participants n=5 Participants
Age, Continuous	64.4 years STANDARD_DEVIATION 7.94 • n=5 Participants	64.6 years STANDARD_DEVIATION 8.01 • n=7 Participants	64.4 years STANDARD_DEVIATION 7.96 • n=5 Participants
Sex: Female, Male Female	341 Participants n=5 Participants	177 Participants n=7 Participants	518 Participants n=5 Participants
Sex: Female, Male Male	792 Participants n=5 Participants	390 Participants n=7 Participants	1182 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	166 Participants n=5 Participants	93 Participants n=7 Participants	259 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	967 Participants n=5 Participants	474 Participants n=7 Participants	1441 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	98 Participants n=5 Participants	54 Participants n=7 Participants	152 Participants n=5 Participants
Race (NIH/OMB) Asian	108 Participants n=5 Participants	55 Participants n=7 Participants	163 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Black or African American	46 Participants n=5 Participants	28 Participants n=7 Participants	74 Participants n=5 Participants
Race (NIH/OMB) White	879 Participants n=5 Participants	430 Participants n=7 Participants	1309 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Canada	67 participants n=5 Participants	24 participants n=7 Participants	91 participants n=5 Participants
Region of Enrollment Netherlands	36 participants n=5 Participants	18 participants n=7 Participants	54 participants n=5 Participants
Region of Enrollment South Korea	48 participants n=5 Participants	26 participants n=7 Participants	74 participants n=5 Participants
Region of Enrollment United States	397 participants n=5 Participants	205 participants n=7 Participants	602 participants n=5 Participants
Region of Enrollment Czechia	118 participants n=5 Participants	52 participants n=7 Participants	170 participants n=5 Participants
Region of Enrollment Taiwan	46 participants n=5 Participants	20 participants n=7 Participants	66 participants n=5 Participants
Region of Enrollment Denmark	17 participants n=5 Participants	10 participants n=7 Participants	27 participants n=5 Participants
Region of Enrollment Poland	196 participants n=5 Participants	97 participants n=7 Participants	293 participants n=5 Participants
Region of Enrollment Mexico	121 participants n=5 Participants	62 participants n=7 Participants	183 participants n=5 Participants
Region of Enrollment Russia	87 participants n=5 Participants	53 participants n=7 Participants	140 participants n=5 Participants
Cardiovascular Risk Groups Group 1: History of atherosclerotic vascular disease	703 Participants n=5 Participants	362 Participants n=7 Participants	1065 Participants n=5 Participants
Cardiovascular Risk Groups Group 2: History of heart failure	166 Participants n=5 Participants	80 Participants n=7 Participants	246 Participants n=5 Participants
Cardiovascular Risk Groups Group 3: Age >= 55 years with > 2 risk factors	264 Participants n=5 Participants	125 Participants n=7 Participants	389 Participants n=5 Participants
Body Weight	94.59 kg STANDARD_DEVIATION 21.87 • n=5 Participants	92.62 kg STANDARD_DEVIATION 19.999 • n=7 Participants	93.94 kg STANDARD_DEVIATION 20.745 • n=5 Participants
Body Mass Index	32.80 kg/m^2 STANDARD_DEVIATION 6.068 • n=5 Participants	32.24 kg/m^2 STANDARD_DEVIATION 5.751 • n=7 Participants	32.62 kg/m^2 STANDARD_DEVIATION 5.968 • n=5 Participants
Body Mass Index Categories BMI < 25 kg/m^2	86 Participants n=5 Participants	45 Participants n=7 Participants	131 Participants n=5 Participants
Body Mass Index Categories BMI >= 25 kg/m^2	1047 Participants n=5 Participants	522 Participants n=7 Participants	1569 Participants n=5 Participants
Systolic Blood Pressure	134.2 mmHg STANDARD_DEVIATION 16.24 • n=5 Participants	133.7 mmHg STANDARD_DEVIATION 16.18 • n=7 Participants	134.0 mmHg STANDARD_DEVIATION 16.21 • n=5 Participants
Systolic Blood Pressure Groups < 140 mmHg	685 Participants n=5 Participants	352 Participants n=7 Participants	1037 Participants n=5 Participants
Systolic Blood Pressure Groups >= 140 mmHg	448 Participants n=5 Participants	215 Participants n=7 Participants	663 Participants n=5 Participants
Diastolic Blood Pressure	77.1 mmHg STANDARD_DEVIATION 9.94 • n=5 Participants	76.8 mmHg STANDARD_DEVIATION 10.16 • n=7 Participants	77.0 mmHg STANDARD_DEVIATION 10.01 • n=5 Participants
eGFR at Screening	77.93 mL/min/1.73 m^2 STANDARD_DEVIATION 19.475 • n=5 Participants	77.76 mL/min/1.73 m^2 STANDARD_DEVIATION 19.653 • n=7 Participants	77.88 mL/min/1.73 m^2 STANDARD_DEVIATION 19.529 • n=5 Participants
eGFR group < 60 mL/min/1.73 m^2	225 Participants n=5 Participants	109 Participants n=7 Participants	334 Participants n=5 Participants
eGFR group >= 60 mL/min/1.73 m^2	908 Participants n=5 Participants	458 Participants n=7 Participants	1366 Participants n=5 Participants
HbA1c	8.32 % of HbA1c STANDARD_DEVIATION 0.897 • n=5 Participants	8.33 % of HbA1c STANDARD_DEVIATION 0.944 • n=7 Participants	8.32 % of HbA1c STANDARD_DEVIATION 0.913 • n=5 Participants
HbA1c group <= 8.5%	716 Participants n=5 Participants	362 Participants n=7 Participants	1078 Participants n=5 Participants
HbA1c group > 8.5%	417 Participants n=5 Participants	205 Participants n=7 Participants	622 Participants n=5 Participants
Duration of Diabetes from Diagnosis to the date of informed consent	14.87 years STANDARD_DEVIATION 8.635 • n=5 Participants	15.23 years STANDARD_DEVIATION 9.253 • n=7 Participants	14.99 years STANDARD_DEVIATION 8.845 • n=5 Participants
Insulin Use at Baseline Yes	610 Participants n=5 Participants	292 Participants n=7 Participants	902 Participants n=5 Participants
Insulin Use at Baseline No	523 Participants n=5 Participants	275 Participants n=7 Participants	798 Participants n=5 Participants
Use of Anti-Diabetic Treatment at Baseline Yes	1125 Participants n=5 Participants	564 Participants n=7 Participants	1689 Participants n=5 Participants
Use of Anti-Diabetic Treatment at Baseline No	8 Participants n=5 Participants	3 Participants n=7 Participants	11 Participants n=5 Participants
NT-proBNP	391.9 pmol/L STANDARD_DEVIATION 760.75 • n=5 Participants	264.0 pmol/L STANDARD_DEVIATION 427.15 • n=7 Participants	346.1 pmol/L STANDARD_DEVIATION 661.93 • n=5 Participants
Left Ventricular Ejection Fraction	49.2 % of Left Ventricular Ejection Fraction STANDARD_DEVIATION 14.13 • n=5 Participants	50.8 % of Left Ventricular Ejection Fraction STANDARD_DEVIATION 12.95 • n=7 Participants	49.8 % of Left Ventricular Ejection Fraction STANDARD_DEVIATION 13.74 • n=5 Participants

PRIMARY outcome

Timeframe: 24 weeks

Population: Number of subjects with a value at baseline and at Week 24.

The primary efficacy objective of this trial is to evaluate the placebo-adjusted change in HbA1c from baseline after 24 weeks of treatment with 20 mg bexagliflozin tablets in type 2 diabetic subjects with increased risk of cardiovascular adverse events.

Outcome measures

Measure	Bexagliflozin Tablets, 20 mg n=1046 Participants Each subject will receive bexagliflozin 20 mg once daily for the duration of the study. Bexagliflozin: 20 mg, tablet	Placebo Tablets n=531 Participants Each subject will receive placebo (inactive tablet) once daily for the duration of the study. Placebo: 20 mg tablet to match active comparator	Subjects With HF History: Bexagliflozin Tablets, 20 mg Each subject will receive bexagliflozin 20 mg once daily for the duration of the study. Bexagliflozin: 20 mg, tablet This group includes subjects who reported a history of heart failure and randomized to the bexagliflozin arm.	Subjects With HF History: Placebo Each subject will receive placebo (inactive tablet) once daily for the duration of the study. Placebo: 20 mg tablet to match active comparator This group includes subjects who reported a history of heart failure and randomized to the placebo arm.
Change in HbA1c From Baseline to Week 24	-0.85 percentage of glycated hemoglobin Interval -0.9 to -0.8	-0.37 percentage of glycated hemoglobin Interval -0.44 to -0.3	—	—

SECONDARY outcome

Timeframe: 24 weeks

Population: Number of subjects with a value at baseline and at week 24.

To evaluate the effect of 20 mg bexagliflozin on the change in HbA1c from baseline to week 24 in randomized subjects who have been prescribed insulin to control their diabetes

Outcome measures

Measure	Bexagliflozin Tablets, 20 mg n=561 Participants Each subject will receive bexagliflozin 20 mg once daily for the duration of the study. Bexagliflozin: 20 mg, tablet	Placebo Tablets n=273 Participants Each subject will receive placebo (inactive tablet) once daily for the duration of the study. Placebo: 20 mg tablet to match active comparator	Subjects With HF History: Bexagliflozin Tablets, 20 mg Each subject will receive bexagliflozin 20 mg once daily for the duration of the study. Bexagliflozin: 20 mg, tablet This group includes subjects who reported a history of heart failure and randomized to the bexagliflozin arm.	Subjects With HF History: Placebo Each subject will receive placebo (inactive tablet) once daily for the duration of the study. Placebo: 20 mg tablet to match active comparator This group includes subjects who reported a history of heart failure and randomized to the placebo arm.
Change From Baseline in HbA1c at Week 24 for Subjects Who Have Been Prescribed Insulin	-0.84 Percentage of HbA1c Interval -0.92 to -0.77	-0.32 Percentage of HbA1c Interval -0.43 to -0.22	—	—

SECONDARY outcome

Timeframe: 48 weeks

Population: Number of subjects with a value at baseline and at Week 48 is included.

To evaluate the effect of 20 mg bexagliflozin on the change in body weight from baseline to week 48 in randomized subjects with a BMI ≥ 25 kg/m2 compared to placebo

Outcome measures

Measure	Bexagliflozin Tablets, 20 mg n=922 Participants Each subject will receive bexagliflozin 20 mg once daily for the duration of the study. Bexagliflozin: 20 mg, tablet	Placebo Tablets n=456 Participants Each subject will receive placebo (inactive tablet) once daily for the duration of the study. Placebo: 20 mg tablet to match active comparator	Subjects With HF History: Bexagliflozin Tablets, 20 mg Each subject will receive bexagliflozin 20 mg once daily for the duration of the study. Bexagliflozin: 20 mg, tablet This group includes subjects who reported a history of heart failure and randomized to the bexagliflozin arm.	Subjects With HF History: Placebo Each subject will receive placebo (inactive tablet) once daily for the duration of the study. Placebo: 20 mg tablet to match active comparator This group includes subjects who reported a history of heart failure and randomized to the placebo arm.
Change in Body Weight From Baseline to Week 48	-3.03 kg Interval -3.27 to -2.8	-0.38 kg Interval -0.72 to -0.04	—	—

SECONDARY outcome

Timeframe: 24 weeks

Population: Number of subjects with a value at baseline and at week 24

To evaluate the effect of 20 mg bexagliflozin on the change in systolic blood pressure (SBP) from baseline to week 24 in subjects with baseline systolic blood pressure ≥ 140 mmHg compared to placebo

Outcome measures

Measure	Bexagliflozin Tablets, 20 mg n=417 Participants Each subject will receive bexagliflozin 20 mg once daily for the duration of the study. Bexagliflozin: 20 mg, tablet	Placebo Tablets n=204 Participants Each subject will receive placebo (inactive tablet) once daily for the duration of the study. Placebo: 20 mg tablet to match active comparator	Subjects With HF History: Bexagliflozin Tablets, 20 mg Each subject will receive bexagliflozin 20 mg once daily for the duration of the study. Bexagliflozin: 20 mg, tablet This group includes subjects who reported a history of heart failure and randomized to the bexagliflozin arm.	Subjects With HF History: Placebo Each subject will receive placebo (inactive tablet) once daily for the duration of the study. Placebo: 20 mg tablet to match active comparator This group includes subjects who reported a history of heart failure and randomized to the placebo arm.
Change in Systolic Blood Pressure From Baseline to Week 24 in Subjects Hypertensive at Baseline	-9.83 mm Hg Interval -11.28 to -8.38	-6.87 mm Hg Interval -8.95 to -4.78	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (week 0) and weeks 6, 12, 24, 36, 48, 72, 96, 120, 144 and 168

Population: Number of subjects with a value at baseline and at the specified visit.

To assess the effect of 20 mg bexagliflozin treatment on the change in HbA1c from baseline versus placebo over time up to 168 weeks

Outcome measures

Measure	Bexagliflozin Tablets, 20 mg n=1133 Participants Each subject will receive bexagliflozin 20 mg once daily for the duration of the study. Bexagliflozin: 20 mg, tablet	Placebo Tablets n=567 Participants Each subject will receive placebo (inactive tablet) once daily for the duration of the study. Placebo: 20 mg tablet to match active comparator	Subjects With HF History: Bexagliflozin Tablets, 20 mg Each subject will receive bexagliflozin 20 mg once daily for the duration of the study. Bexagliflozin: 20 mg, tablet This group includes subjects who reported a history of heart failure and randomized to the bexagliflozin arm.	Subjects With HF History: Placebo Each subject will receive placebo (inactive tablet) once daily for the duration of the study. Placebo: 20 mg tablet to match active comparator This group includes subjects who reported a history of heart failure and randomized to the placebo arm.
Change in HbA1c From Baseline Over Time Week 6	-0.69 Percentage of HbA1c Interval -0.72 to -0.65	-0.24 Percentage of HbA1c Interval -0.28 to -0.19	—	—
Change in HbA1c From Baseline Over Time Week 12	-0.89 Percentage of HbA1c Interval -0.94 to -0.85	-0.34 Percentage of HbA1c Interval -0.39 to -0.28	—	—
Change in HbA1c From Baseline Over Time Week 24	-0.84 Percentage of HbA1c Interval -0.89 to -0.79	-0.37 Percentage of HbA1c Interval -0.45 to -0.3	—	—
Change in HbA1c From Baseline Over Time Week 36	-0.86 Percentage of HbA1c Interval -0.92 to -0.81	-0.39 Percentage of HbA1c Interval -0.47 to -0.32	—	—
Change in HbA1c From Baseline Over Time Week 48	-0.84 Percentage of HbA1c Interval -0.9 to -0.79	-0.38 Percentage of HbA1c Interval -0.46 to -0.3	—	—
Change in HbA1c From Baseline Over Time Week 72	-0.76 Percentage of HbA1c Interval -0.83 to -0.7	-0.34 Percentage of HbA1c Interval -0.44 to -0.25	—	—
Change in HbA1c From Baseline Over Time Week 96	-0.68 Percentage of HbA1c Interval -0.75 to -0.62	-0.29 Percentage of HbA1c Interval -0.39 to -0.2	—	—
Change in HbA1c From Baseline Over Time Week 120	-0.65 Percentage of HbA1c Interval -0.73 to -0.58	-0.22 Percentage of HbA1c Interval -0.33 to -0.11	—	—
Change in HbA1c From Baseline Over Time Week 144	-0.62 Percentage of HbA1c Interval -0.71 to -0.53	-0.23 Percentage of HbA1c Interval -0.37 to -0.1	—	—
Change in HbA1c From Baseline Over Time Week 168	-0.56 Percentage of HbA1c Interval -0.67 to -0.45	-0.29 Percentage of HbA1c Interval -0.46 to -0.13	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (week 0) and weeks 6, 12, 24, 36, 48, 72, 96, 120, 144 and 168

Population: Number of subjects with a value at baseline and at the specified visit.

To evaluate the effect of bexagliflozin treatment on the change in fasting plasma glucose (FPG) versus placebo over time up to 168 weeks

Outcome measures

Measure	Bexagliflozin Tablets, 20 mg n=1133 Participants Each subject will receive bexagliflozin 20 mg once daily for the duration of the study. Bexagliflozin: 20 mg, tablet	Placebo Tablets n=567 Participants Each subject will receive placebo (inactive tablet) once daily for the duration of the study. Placebo: 20 mg tablet to match active comparator	Subjects With HF History: Bexagliflozin Tablets, 20 mg Each subject will receive bexagliflozin 20 mg once daily for the duration of the study. Bexagliflozin: 20 mg, tablet This group includes subjects who reported a history of heart failure and randomized to the bexagliflozin arm.	Subjects With HF History: Placebo Each subject will receive placebo (inactive tablet) once daily for the duration of the study. Placebo: 20 mg tablet to match active comparator This group includes subjects who reported a history of heart failure and randomized to the placebo arm.
Change in Fasting Plasma Glucose Over Time Week 6	-1.28 mmol/L Interval -1.4 to -1.16	0.07 mmol/L Interval -0.1 to 0.24	—	—
Change in Fasting Plasma Glucose Over Time Week 12	-1.33 mmol/L Interval -1.46 to -1.21	0.06 mmol/L Interval -0.12 to 0.23	—	—
Change in Fasting Plasma Glucose Over Time Week 24	-1.43 mmol/L Interval -1.56 to -1.3	-0.05 mmol/L Interval -0.23 to 0.13	—	—
Change in Fasting Plasma Glucose Over Time Week 36	-1.21 mmol/L Interval -1.36 to -1.06	-0.06 mmol/L Interval -0.27 to 0.15	—	—
Change in Fasting Plasma Glucose Over Time Week 48	-1.36 mmol/L Interval -1.5 to -1.21	-0.12 mmol/L Interval -0.33 to 0.08	—	—
Change in Fasting Plasma Glucose Over Time Week 72	-1.14 mmol/L Interval -1.3 to -0.98	-0.15 mmol/L Interval -0.38 to 0.07	—	—
Change in Fasting Plasma Glucose Over Time Week 96	-1.16 mmol/L Interval -1.32 to -0.99	0.04 mmol/L Interval -0.2 to 0.29	—	—
Change in Fasting Plasma Glucose Over Time Week 120	-0.90 mmol/L Interval -1.09 to -0.71	0.25 mmol/L Interval -0.02 to 0.53	—	—
Change in Fasting Plasma Glucose Over Time Week 144	-1.03 mmol/L Interval -1.24 to -0.81	-0.40 mmol/L Interval -0.72 to -0.08	—	—
Change in Fasting Plasma Glucose Over Time Week 168	-1.06 mmol/L Interval -1.39 to -0.73	-0.55 mmol/L Interval -1.04 to -0.07	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 week

To measure the proportion of subjects requiring an intensification of hypoglycemic agent in the bexagliflozin arm versus placebo during 24 week period

Outcome measures

Measure	Bexagliflozin Tablets, 20 mg n=1133 Participants Each subject will receive bexagliflozin 20 mg once daily for the duration of the study. Bexagliflozin: 20 mg, tablet	Placebo Tablets n=567 Participants Each subject will receive placebo (inactive tablet) once daily for the duration of the study. Placebo: 20 mg tablet to match active comparator	Subjects With HF History: Bexagliflozin Tablets, 20 mg Each subject will receive bexagliflozin 20 mg once daily for the duration of the study. Bexagliflozin: 20 mg, tablet This group includes subjects who reported a history of heart failure and randomized to the bexagliflozin arm.	Subjects With HF History: Placebo Each subject will receive placebo (inactive tablet) once daily for the duration of the study. Placebo: 20 mg tablet to match active comparator This group includes subjects who reported a history of heart failure and randomized to the placebo arm.
Proportion of Subjects Requiring an Intensification of Hypoglycemic Agent and Time to First Intensification	0.06 Proportion of participants Interval 0.05 to 0.08	0.18 Proportion of participants Interval 0.15 to 0.21	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Duration of study (168 weeks)

To measure the proportion of subjects requiring an intensification of hypoglycemic agent in the bexagliflozin arm versus placebo during the entire study period

Outcome measures

Measure	Bexagliflozin Tablets, 20 mg n=1133 Participants Each subject will receive bexagliflozin 20 mg once daily for the duration of the study. Bexagliflozin: 20 mg, tablet	Placebo Tablets n=567 Participants Each subject will receive placebo (inactive tablet) once daily for the duration of the study. Placebo: 20 mg tablet to match active comparator	Subjects With HF History: Bexagliflozin Tablets, 20 mg Each subject will receive bexagliflozin 20 mg once daily for the duration of the study. Bexagliflozin: 20 mg, tablet This group includes subjects who reported a history of heart failure and randomized to the bexagliflozin arm.	Subjects With HF History: Placebo Each subject will receive placebo (inactive tablet) once daily for the duration of the study. Placebo: 20 mg tablet to match active comparator This group includes subjects who reported a history of heart failure and randomized to the placebo arm.
Proportion of Subjects Requiring an Intensification of Hypoglycemic Agent and Time to First Intensification	0.06 Proportion of participants Interval 0.05 to 0.08	0.18 Proportion of participants Interval 0.15 to 0.21	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 weeks

To measure the proportion of subjects requiring a relaxation of hypoglycemic agent in the bexagliflozin arm versus placebo during 24 week period

Outcome measures

Measure	Bexagliflozin Tablets, 20 mg n=1133 Participants Each subject will receive bexagliflozin 20 mg once daily for the duration of the study. Bexagliflozin: 20 mg, tablet	Placebo Tablets n=567 Participants Each subject will receive placebo (inactive tablet) once daily for the duration of the study. Placebo: 20 mg tablet to match active comparator	Subjects With HF History: Bexagliflozin Tablets, 20 mg Each subject will receive bexagliflozin 20 mg once daily for the duration of the study. Bexagliflozin: 20 mg, tablet This group includes subjects who reported a history of heart failure and randomized to the bexagliflozin arm.	Subjects With HF History: Placebo Each subject will receive placebo (inactive tablet) once daily for the duration of the study. Placebo: 20 mg tablet to match active comparator This group includes subjects who reported a history of heart failure and randomized to the placebo arm.
Proportion of Subjects Requiring a Relaxation of Hypoglycemic Agent	0.09 Proportion of participants Interval 0.08 to 0.11	0.05 Proportion of participants Interval 0.03 to 0.07	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Duration of study (168 weeks)

To measure the proportion of subjects requiring a relaxation of hypoglycemic agent in the bexagliflozin arm versus placebo during the entire study

Outcome measures

Measure	Bexagliflozin Tablets, 20 mg n=1133 Participants Each subject will receive bexagliflozin 20 mg once daily for the duration of the study. Bexagliflozin: 20 mg, tablet	Placebo Tablets n=567 Participants Each subject will receive placebo (inactive tablet) once daily for the duration of the study. Placebo: 20 mg tablet to match active comparator	Subjects With HF History: Bexagliflozin Tablets, 20 mg Each subject will receive bexagliflozin 20 mg once daily for the duration of the study. Bexagliflozin: 20 mg, tablet This group includes subjects who reported a history of heart failure and randomized to the bexagliflozin arm.	Subjects With HF History: Placebo Each subject will receive placebo (inactive tablet) once daily for the duration of the study. Placebo: 20 mg tablet to match active comparator This group includes subjects who reported a history of heart failure and randomized to the placebo arm.
Proportion of Subjects Requiring a Relaxation of Hypoglycemic Agent	0.09 Proportion of participants Interval 0.08 to 0.11	0.05 Proportion of participants Interval 0.03 to 0.07	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Duration of study (168 weeks)

To measure the incidence of hospitalization for heart failure among all subjects and among subjects who have a history of heart failure at baseline

Outcome measures

Measure	Bexagliflozin Tablets, 20 mg n=1133 Participants Each subject will receive bexagliflozin 20 mg once daily for the duration of the study. Bexagliflozin: 20 mg, tablet	Placebo Tablets n=567 Participants Each subject will receive placebo (inactive tablet) once daily for the duration of the study. Placebo: 20 mg tablet to match active comparator	Subjects With HF History: Bexagliflozin Tablets, 20 mg n=302 Participants Each subject will receive bexagliflozin 20 mg once daily for the duration of the study. Bexagliflozin: 20 mg, tablet This group includes subjects who reported a history of heart failure and randomized to the bexagliflozin arm.	Subjects With HF History: Placebo n=151 Participants Each subject will receive placebo (inactive tablet) once daily for the duration of the study. Placebo: 20 mg tablet to match active comparator This group includes subjects who reported a history of heart failure and randomized to the placebo arm.
Proportion of Participants With Incidence of Hospitalization for Heart Failure	0.01 Proportion of participants Interval 0.01 to 0.02	0.02 Proportion of participants Interval 0.01 to 0.03	0.05 Proportion of participants Interval 0.03 to 0.08	0.09 Proportion of participants Interval 0.05 to 0.15

Adverse Events

Bexagliflozin Tablets, 20 mg

Serious events: 373 serious events

Other events: 739 other events

Deaths: 39 deaths

Placebo Tablets

Serious events: 208 serious events

Other events: 386 other events

Deaths: 26 deaths

Serious adverse events

Measure	Bexagliflozin Tablets, 20 mg n=1132 participants at risk Each subject will receive bexagliflozin 20 mg once daily for the duration of the study. Bexagliflozin: 20 mg, tablet	Placebo Tablets n=567 participants at risk Each subject will receive placebo (inactive tablet) once daily for the duration of the study. Placebo: 20 mg tablet to match active comparator
Gastrointestinal disorders Pancreatitis acute	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Gastrointestinal disorders Rectal perforation	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Gastrointestinal disorders Rectal polyp	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Gastrointestinal disorders Subileus	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.88% 10/1132 • Number of events 11 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.53% 3/567 • Number of events 6 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.80% 9/1132 • Number of events 10 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.53% 3/567 • Number of events 4 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.18% 2/1132 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Musculoskeletal and connective tissue disorders Spinal column stenosis	0.27% 3/1132 • Number of events 3 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.53% 6/1132 • Number of events 6 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.35% 4/1132 • Number of events 4 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Respiratory, thoracic and mediastinal disorders Acute pulmonary edema	0.18% 2/1132 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Musculoskeletal and connective tissue disorders Arthralgia	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.35% 2/567 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Respiratory, thoracic and mediastinal disorders Aspiration	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Respiratory, thoracic and mediastinal disorders Asthma	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Respiratory, thoracic and mediastinal disorders Epistaxis	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Respiratory, thoracic and mediastinal disorders Haemothorax	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Respiratory, thoracic and mediastinal disorders Hypoxia	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Respiratory, thoracic and mediastinal disorders Lung disorder	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Respiratory, thoracic and mediastinal disorders Nasal polyps	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Respiratory, thoracic and mediastinal disorders Pleurisy	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Respiratory, thoracic and mediastinal disorders Vocal cord polyp	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.53% 3/567 • Number of events 3 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.18% 2/1132 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Transitional cell carcinoma	0.27% 3/1132 • Number of events 3 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive ductal breast carcinoma	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lipoma	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	0.18% 2/1132 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.18% 2/1132 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma gastric	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma of colon	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma pancreas	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adrenal adenoma	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) B-cell lymphoma	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Biliary cancer metastatic	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Musculoskeletal and connective tissue disorders Arthropathy	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Musculoskeletal and connective tissue disorders Bursitis	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Musculoskeletal and connective tissue disorders Cervical spinal stenosis	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Musculoskeletal and connective tissue disorders Dupuytren's contracture	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Musculoskeletal and connective tissue disorders Immunoglobulin G4 related sclerosing disease	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Musculoskeletal and connective tissue disorders Intervertebral disc disorder	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Musculoskeletal and connective tissue disorders Joint instability	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Musculoskeletal and connective tissue disorders Neuropathic arthropathy	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Musculoskeletal and connective tissue disorders Osteochondrosis	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Musculoskeletal and connective tissue disorders Scoliosis	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Musculoskeletal and connective tissue disorders Tenosynovitis	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Gastrointestinal disorders Gastrointestinal haemorrhage	0.18% 2/1132 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.71% 4/567 • Number of events 4 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Gastrointestinal disorders Diarrhoea	0.35% 4/1132 • Number of events 4 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Gastrointestinal disorders Colitis	0.27% 3/1132 • Number of events 3 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Gastrointestinal disorders Diverticulum	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.35% 2/567 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Gastrointestinal disorders Gastric ulcer	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.35% 2/567 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Gastrointestinal disorders Gastrooesophageal reflux disease	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.35% 2/567 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Gastrointestinal disorders Small intestinal obstruction	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.35% 2/567 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Gastrointestinal disorders Umbilical hernia	0.18% 2/1132 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.18% 2/1132 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Gastrointestinal disorders Large intestine polyp	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Gastrointestinal disorders Abdominal pain	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Gastrointestinal disorders Abdominal pain upper	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Gastrointestinal disorders Anal fistula	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Gastrointestinal disorders Barret's oesophagus	0.09% 1/1132 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Gastrointestinal disorders Colitis ischaemic	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Gastrointestinal disorders Crohn's disease	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Gastrointestinal disorders Duodenal ulcer haemorrhage	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Gastrointestinal disorders Enterocutaneous fistula	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Gastrointestinal disorders Fecal incontinence	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Gastrointestinal disorders Gastric polyps	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Gastrointestinal disorders Gastrointestinal polyp haemorrhage	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Gastrointestinal disorders Hiatus hernia	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Gastrointestinal disorders Incarcerated inguinal hernia	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Gastrointestinal disorders Inguinal hernia	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Gastrointestinal disorders Intra-abdominal haematoma	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Gastrointestinal disorders Mesenteric vein thrombosis	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Cardiac disorders Angina unstable	2.7% 31/1132 • Number of events 39 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	3.4% 19/567 • Number of events 22 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Cardiac disorders Acute myocardial infarction	2.7% 31/1132 • Number of events 33 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	2.5% 14/567 • Number of events 15 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Cardiac disorders Cardiac failure congestive	1.6% 18/1132 • Number of events 21 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	2.6% 15/567 • Number of events 21 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Cardiac disorders Cardiac failure	1.9% 21/1132 • Number of events 27 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	1.2% 7/567 • Number of events 9 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Cardiac disorders Angina pectoris	1.4% 16/1132 • Number of events 20 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	1.9% 11/567 • Number of events 12 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Cardiac disorders Coronary artery disease	1.9% 21/1132 • Number of events 21 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	1.1% 6/567 • Number of events 6 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Cardiac disorders Atrial fibrillation	1.3% 15/1132 • Number of events 21 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	1.6% 9/567 • Number of events 17 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Cardiac disorders Myocardial infarction	0.97% 11/1132 • Number of events 11 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	2.3% 13/567 • Number of events 13 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Cardiac disorders Cardiac arrest	1.1% 12/1132 • Number of events 12 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.35% 2/567 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Cardiac disorders Cardiac failure chronic	0.44% 5/1132 • Number of events 6 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.71% 4/567 • Number of events 4 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Cardiac disorders Myocardial ischaemia	0.71% 8/1132 • Number of events 8 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Cardiac disorders Ventricular tachycardia	0.27% 3/1132 • Number of events 3 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	1.1% 6/567 • Number of events 7 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Cardiac disorders Coronary artery occlusion	0.27% 3/1132 • Number of events 3 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.53% 3/567 • Number of events 3 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Cardiac disorders Atrial flutter	0.27% 3/1132 • Number of events 3 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.35% 2/567 • Number of events 4 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Cardiac disorders Coronary artery stenosis	0.27% 3/1132 • Number of events 3 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.35% 2/567 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Cardiac disorders Arrhythmia	0.18% 2/1132 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Cardiac disorders Cardiac disorder	0.18% 2/1132 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Cardiac disorders Cardio-respiratory arrest	0.18% 2/1132 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Cardiac disorders Cardiopulmonary arrest	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.35% 2/567 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Cardiac disorders Sinus node dysfunction	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.35% 2/567 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Cardiac disorders Acute coronary syndrome	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.35% 2/567 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Cardiac disorders Aortic valve stenosis	0.18% 2/1132 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Cardiac disorders Bradycardia	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Cardiac disorders Congestive cardiomyopathy	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Cardiac disorders Tachycardia	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.35% 2/567 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Cardiac disorders Ventricular arrhythmia	0.18% 2/1132 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Cardiac disorders Anginal equivalent	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Cardiac disorders Aortic valve disease	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Cardiac disorders Aortic valve incompetence	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Cardiac disorders Atrioventricular block	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Cardiac disorders Cardiac asthma	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Cardiac disorders Cardiac failure acute	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Cardiac disorders Cardiogenic shock	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Cardiac disorders Cardiomyopathy	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Cardiac disorders Cardiorenal syndrome	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Cardiac disorders Heart valve incompetence	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Cardiac disorders Intracardiac thrombus	0.09% 1/1132 • Number of events 3 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Cardiac disorders Ischaemic cardiomyopathy	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Cardiac disorders Left ventricular failure	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Cardiac disorders Mitral valve incompetence	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Cardiac disorders Pericardial effusion	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Cardiac disorders Sinus tachycardia	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Cardiac disorders Ventricular fibrillation	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Pneumonia	0.97% 11/1132 • Number of events 11 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	1.8% 10/567 • Number of events 10 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Cellulitis	0.80% 9/1132 • Number of events 11 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.35% 2/567 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Osteomyelitis	0.88% 10/1132 • Number of events 13 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Sepsis	0.80% 9/1132 • Number of events 9 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Urinary tract infection	0.53% 6/1132 • Number of events 6 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.53% 3/567 • Number of events 3 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Gangrene	0.35% 4/1132 • Number of events 5 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.53% 3/567 • Number of events 4 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Diverticulitis	0.27% 3/1132 • Number of events 3 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.53% 3/567 • Number of events 3 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Appendicitis	0.18% 2/1132 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.35% 2/567 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Localised infection	0.35% 4/1132 • Number of events 4 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Pyelonephritis	0.27% 3/1132 • Number of events 3 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Endocarditis	0.27% 3/1132 • Number of events 3 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Influenza	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.35% 2/567 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Septic shock	0.27% 3/1132 • Number of events 3 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Urosepsis	0.18% 2/1132 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Abdominal abscess	0.18% 2/1132 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Bacteraemia	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Erysipelas	0.18% 2/1132 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Gastroenteritis	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Gastroenteritis viral	0.18% 2/1132 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Wound infection	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Abdominal wall abscess	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Abscess limb	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Atypical pneumonia	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Biliary tract infection	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Bronchitis	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Bursitis infective	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Chronic sinusitis	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Device related infection	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Diabetic foot infection	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Ear infection	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Emphysematous cholecystitis	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Enterococcal bacteraemia	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Gas gangrene	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Gastroenteritis salmonella	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Hepatitis B	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Infected skin ulcer	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Medical device site joint infection	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Myelitis	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Oesophageal candidiasis	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Peritonitis	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Pneumonia legionella	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Pneumonia streptococcal	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Postoperative wound infection	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Pyelonephritis acute	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Scrotal abscess	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Skin infection	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Subcutaneous abscess	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Viral infection	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Nervous system disorders Cerebrovascular accident	1.3% 15/1132 • Number of events 15 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	1.2% 7/567 • Number of events 7 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Nervous system disorders Ischaemic stroke	0.88% 10/1132 • Number of events 11 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.71% 4/567 • Number of events 4 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Nervous system disorders Transient ischaemic attack	0.53% 6/1132 • Number of events 7 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.88% 5/567 • Number of events 6 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Nervous system disorders Carotid artery stenosis	0.62% 7/1132 • Number of events 9 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.53% 3/567 • Number of events 3 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Nervous system disorders Syncope	0.35% 4/1132 • Number of events 4 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.71% 4/567 • Number of events 4 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Nervous system disorders Subarachnoid haemorrhage	0.27% 3/1132 • Number of events 3 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Nervous system disorders Carpal tunnel syndrome	0.18% 2/1132 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Nervous system disorders Cerebral infarction	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Nervous system disorders Dizziness	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Nervous system disorders Presyncope	0.18% 2/1132 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Nervous system disorders Sciatica	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Nervous system disorders Aphasia	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Nervous system disorders Brain stem infarction	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Nervous system disorders Central nervous system haemorrhage	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Nervous system disorders Cerebral artery stenosis	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Nervous system disorders Cerebral artery thrombosis	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Nervous system disorders Cervical myelopathy	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Nervous system disorders Cervical radiculopathy	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Nervous system disorders Encephalopathy	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Nervous system disorders Epilepsy	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Nervous system disorders Haemorrhage intracranial	0.09% 1/1132 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Nervous system disorders Headache	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Nervous system disorders Hemiparesis	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Nervous system disorders Hypoaesthesia	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Nervous system disorders Miller Fisher syndrome	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Nervous system disorders Myasthenia gravis	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Nervous system disorders Neurological symptom	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Nervous system disorders Normal pressure hydrocephalus	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Nervous system disorders Paraesthesia	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Nervous system disorders Parkinson's disease	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Nervous system disorders Polyneuropathy	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Nervous system disorders Radiculopathy	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Nervous system disorders Thalamic infarction	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Vascular disorders Peripheral ischaemia	0.97% 11/1132 • Number of events 12 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	1.2% 7/567 • Number of events 8 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Vascular disorders Peripheral arterial occlusive disease	0.71% 8/1132 • Number of events 11 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	1.1% 6/567 • Number of events 8 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Vascular disorders Hypotension	0.44% 5/1132 • Number of events 5 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Vascular disorders Hypertension	0.18% 2/1132 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.35% 2/567 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Vascular disorders Orthostatic hypotension	0.27% 3/1132 • Number of events 3 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Vascular disorders Arteriosclerosis	0.18% 2/1132 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Vascular disorders Femoral artery occlusion	0.27% 3/1132 • Number of events 3 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Vascular disorders Hypertensive crisis	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.35% 2/567 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Vascular disorders Intermittent claudication	0.09% 1/1132 • Number of events 3 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.35% 2/567 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Vascular disorders Peripheral vascular disorder	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.35% 2/567 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Vascular disorders Deep vein thrombosis	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Vascular disorders Peripheral artery stenosis	0.18% 2/1132 • Number of events 3 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Vascular disorders Peripheral artery thrombosis	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Vascular disorders Aortic stenosis	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Vascular disorders Hypertensive emergency	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Vascular disorders Iliac artery occlusion	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Vascular disorders Leriche syndrome	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Vascular disorders Lymphoedema	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Vascular disorders Necrosis ischaemic	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Vascular disorders Subclavian vein thrombosis	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Vascular disorders Varicose vein	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Vascular disorders Venous thrombosis	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Musculoskeletal and connective tissue disorders Osteoarthritis	1.3% 15/1132 • Number of events 17 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.71% 4/567 • Number of events 4 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.18% 2/1132 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.35% 2/567 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Musculoskeletal and connective tissue disorders Arthritis	0.18% 2/1132 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Carcinoid tumour of the appendix	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cervix carcinoma	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer recurrent	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colorectal adenocarcinoma	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Endometrial adenocarcinoma	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric adenoma	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic neoplasm	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatocellular carcinoma	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive papillary breast carcinoma	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm of ampulla of Vater	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic renal cell carcinoma	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myelodysplastic syndrome	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myeloproliferative disorder	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-small cell lung cancer	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian cancer	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Papillary cystadenoma lymphomatosum	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pituitary tumour benign	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Polycythaemia vera	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cancer	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cancer metastatic	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of lung	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Metabolism and nutrition disorders Hypoglycaemia	1.2% 14/1132 • Number of events 15 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	1.4% 8/567 • Number of events 10 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Metabolism and nutrition disorders Dehydration	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.53% 3/567 • Number of events 3 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Metabolism and nutrition disorders Hyperkalaemia	0.27% 3/1132 • Number of events 3 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Metabolism and nutrition disorders Diabetic ketoacidosis	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.53% 3/567 • Number of events 4 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Metabolism and nutrition disorders Gout	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.35% 2/567 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.18% 2/1132 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.35% 2/567 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Metabolism and nutrition disorders Hypokalaemia	0.18% 2/1132 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Metabolism and nutrition disorders Metabolic acidosis	0.18% 2/1132 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Metabolism and nutrition disorders Diabetic complication	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Metabolism and nutrition disorders Latent autoimmune diabetes in adults	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Metabolism and nutrition disorders Obesity	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Injury, poisoning and procedural complications Contusion	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.35% 2/567 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Injury, poisoning and procedural complications Femur fracture	0.27% 3/1132 • Number of events 3 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Injury, poisoning and procedural complications Hip fracture	0.18% 2/1132 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Injury, poisoning and procedural complications Patella fracture	0.27% 3/1132 • Number of events 3 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Injury, poisoning and procedural complications Concussion	0.18% 2/1132 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Injury, poisoning and procedural complications Foot fracture	0.18% 2/1132 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Injury, poisoning and procedural complications Joint injury	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.35% 2/567 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Injury, poisoning and procedural complications Rib fracture	0.18% 2/1132 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Injury, poisoning and procedural complications Spinal fracture	0.18% 2/1132 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Injury, poisoning and procedural complications Anastomotic ulcer	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Injury, poisoning and procedural complications Compression fracture	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Injury, poisoning and procedural complications Craniocerebral injury	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Injury, poisoning and procedural complications Fall	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Injury, poisoning and procedural complications Fibula fracture	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Injury, poisoning and procedural complications Humerus fracture	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Injury, poisoning and procedural complications Laceration	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Injury, poisoning and procedural complications Ligament rupture	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Injury, poisoning and procedural complications Limb injury	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Injury, poisoning and procedural complications Lower limb fracture	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Injury, poisoning and procedural complications Meniscus injury	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Injury, poisoning and procedural complications Pneumoconiosis	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Injury, poisoning and procedural complications Post procedural complication	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Injury, poisoning and procedural complications Post procedural haemorrhage	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Injury, poisoning and procedural complications Procedural pain	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Injury, poisoning and procedural complications Pulmonary contusion	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Injury, poisoning and procedural complications Seroma	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Injury, poisoning and procedural complications Subdural haematoma	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Injury, poisoning and procedural complications Subdural haemorrhage	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Injury, poisoning and procedural complications Vascular pseudoaneurysm	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
General disorders Non-cardiac chest pain	0.53% 6/1132 • Number of events 7 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.88% 5/567 • Number of events 5 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
General disorders Chest pain	0.53% 6/1132 • Number of events 7 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.53% 3/567 • Number of events 3 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
General disorders Necrosis	0.27% 3/1132 • Number of events 3 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
General disorders Death	0.18% 2/1132 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
General disorders Device malfunction	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
General disorders Oedema peripheral	0.18% 2/1132 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
General disorders Adverse drug reaction	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
General disorders Asthenia	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
General disorders Chest discomfort	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
General disorders Complication associated with device	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
General disorders Impaired healing	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
General disorders Medical device complication	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
General disorders Sudden cardiac death	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Renal and urinary disorders Acute kidney injury	0.80% 9/1132 • Number of events 10 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.71% 4/567 • Number of events 4 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Renal and urinary disorders Nephrolithiasis	0.27% 3/1132 • Number of events 4 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.35% 2/567 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Renal and urinary disorders Calculus ureteric	0.18% 2/1132 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Renal and urinary disorders Calculus urinary	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Renal and urinary disorders Chronic kidney disease	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Renal and urinary disorders Haematuria	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Renal and urinary disorders Obstructive uropathy	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Renal and urinary disorders Renal colic	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Renal and urinary disorders Urinary retention	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Hepatobiliary disorders Cholecystitis	0.18% 2/1132 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Hepatobiliary disorders Cholangitis	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Hepatobiliary disorders Cholecystitis acute	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Hepatobiliary disorders Cholelithiasis	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.35% 2/567 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Hepatobiliary disorders Bile duct stone	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Hepatobiliary disorders Cholangitis acute	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Hepatobiliary disorders Hepatic cirrhosis	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Skin and subcutaneous tissue disorders Skin ulcer	0.18% 2/1132 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.53% 3/567 • Number of events 6 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Skin and subcutaneous tissue disorders Diabetic foot	0.27% 3/1132 • Number of events 3 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Skin and subcutaneous tissue disorders Dermatitis contact	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Skin and subcutaneous tissue disorders Excessive granulation tissue	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Reproductive system and breast disorders Benign prostatic hyperplasia	0.27% 3/1132 • Number of events 3 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Reproductive system and breast disorders Erectile dysfunction	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Reproductive system and breast disorders Cervix disorder	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Reproductive system and breast disorders Oedema genital	0.09% 1/1132 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Reproductive system and breast disorders Prostatism	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Reproductive system and breast disorders Prostatitis	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Reproductive system and breast disorders Uterine prolapse	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Eye disorders Cataract	0.27% 3/1132 • Number of events 4 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Eye disorders Corneal lesion	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Eye disorders Glaucoma	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Eye disorders Keratopathy	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Eye disorders Lens dislocation	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Eye disorders Retinal vein thrombosis	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Blood and lymphatic system disorders Anaemia	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.35% 2/567 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Blood and lymphatic system disorders Thrombocytopenia	0.18% 2/1132 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Blood and lymphatic system disorders Haemorrhagic anaemia	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Blood and lymphatic system disorders Iron deficiency anaemia	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Surgical and medical procedures Cardiac pacemaker battery replacement	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Surgical and medical procedures Cardiac pacemaker replacement	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Surgical and medical procedures Implantable defibrillator insertion	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Surgical and medical procedures Prophylaxis	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Surgical and medical procedures Vitrectomy	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Congenital, familial and genetic disorders Hydrocele	0.18% 2/1132 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Congenital, familial and genetic disorders Atrial septal defect	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Congenital, familial and genetic disorders Phimosis	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Psychiatric disorders Bipolar I disorder	0.00% 0/1132 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.18% 1/567 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Psychiatric disorders Delirium	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Psychiatric disorders Suicidal ideation	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Psychiatric disorders Suicide attempt	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Ear and labyrinth disorders Vertigo	0.18% 2/1132 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Ear and labyrinth disorders Vertigo positional	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Investigations Troponin increased	0.18% 2/1132 • Number of events 2 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Investigations Blood creatinine increased	0.09% 1/1132 • Number of events 1 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	0.00% 0/567 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)

Other adverse events

Measure	Bexagliflozin Tablets, 20 mg n=1132 participants at risk Each subject will receive bexagliflozin 20 mg once daily for the duration of the study. Bexagliflozin: 20 mg, tablet	Placebo Tablets n=567 participants at risk Each subject will receive placebo (inactive tablet) once daily for the duration of the study. Placebo: 20 mg tablet to match active comparator
Gastrointestinal disorders Diarrhoea	6.4% 72/1132 • Number of events 90 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	5.5% 31/567 • Number of events 40 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Gastrointestinal disorders Nausea	4.8% 54/1132 • Number of events 64 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	6.5% 37/567 • Number of events 45 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Bronchitis	4.6% 52/1132 • Number of events 65 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	6.0% 34/567 • Number of events 40 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Nasopharyngitis	8.5% 96/1132 • Number of events 115 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	6.9% 39/567 • Number of events 46 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Upper respiratory tract infection	9.9% 112/1132 • Number of events 147 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	9.3% 53/567 • Number of events 82 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Infections and infestations Urinary tract infection	11.3% 128/1132 • Number of events 190 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	10.6% 60/567 • Number of events 96 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Metabolism and nutrition disorders Diabetes mellitus inadequate control	4.3% 49/1132 • Number of events 53 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	5.1% 29/567 • Number of events 37 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Metabolism and nutrition disorders Hyperglycaemia	6.0% 68/1132 • Number of events 181 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	7.2% 41/567 • Number of events 80 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Metabolism and nutrition disorders Hypoglycaemia	42.0% 475/1132 • Number of events 3743 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	43.4% 246/567 • Number of events 1857 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Musculoskeletal and connective tissue disorders Arthralgia	4.3% 49/1132 • Number of events 56 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	5.3% 30/567 • Number of events 37 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Musculoskeletal and connective tissue disorders Back pain	5.8% 66/1132 • Number of events 72 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	5.8% 33/567 • Number of events 36 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)
Vascular disorders Hypertension	4.0% 45/1132 • Number of events 46 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)	6.3% 36/567 • Number of events 38 • Adverse event data were collected from the first dose to the last day of follow up (4 weeks after the End of Treatment visit, an average of 127 weeks)

Additional Information

Albert Collinson

Theracos Sub, LLC

Phone: (508) 630-2129

Email: acollinson@theracos.com

Results disclosure agreements

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