Trial Outcomes & Findings for Study of Effects of Sacubitril/Valsartan vs. Enalapril on Aortic Stiffness in Patients With Mild to Moderate HF With Reduced Ejection Fraction (NCT NCT02874794)
NCT ID: NCT02874794
Last Updated: 2021-01-05
Results Overview
Aortic characteristic impedance, Zc, is the ratio of the change in pressure (dP)produced by a given change in flow (dQ) in early systole, i.e., Zc = dP/dQ. Zc is related directly to aortic wall stiffness and inversely to lumen area.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
465 participants
Primary outcome timeframe
Baseline, Week 12
Results posted on
2021-01-05
Participant Flow
Of 892 patients screened for the study, 465 completed screening and were enrolled. Of the 465 randomized, 1 patient was randomized in error to the sacubitril/valsartan group and was not treated. The Full Analysis Set and Safety Set are based on 464 patients who received treatment.
Participant milestones
| Measure |
Enalapril (Double-Blind Phase)
minimum dose: 2.5mg, BID, oral, tablet. maximum dose: 10 mg, BID, oral tablet. All patients began on Dose Level 1 (2.5mg) and were titrated every two weeks to target Dose level 3 (10mg).
|
Sacubitril/Valsartan (Double-Blind Phase)
minimum dose: 24/26mg, BID, oral, tablet. maximum dose: 97/103mg, BID, oral, tablet. All patients began on Dose Level 1 (24/26mg) and were titrated every two weeks to target Dose level 3 (97/103mg).
|
|---|---|---|
|
Overall Study
STARTED
|
233
|
232
|
|
Overall Study
COMPLETED
|
226
|
221
|
|
Overall Study
NOT COMPLETED
|
7
|
11
|
Reasons for withdrawal
| Measure |
Enalapril (Double-Blind Phase)
minimum dose: 2.5mg, BID, oral, tablet. maximum dose: 10 mg, BID, oral tablet. All patients began on Dose Level 1 (2.5mg) and were titrated every two weeks to target Dose level 3 (10mg).
|
Sacubitril/Valsartan (Double-Blind Phase)
minimum dose: 24/26mg, BID, oral, tablet. maximum dose: 97/103mg, BID, oral, tablet. All patients began on Dose Level 1 (24/26mg) and were titrated every two weeks to target Dose level 3 (97/103mg).
|
|---|---|---|
|
Overall Study
Physician Decision
|
3
|
2
|
|
Overall Study
Withdrawal by Subject
|
2
|
8
|
|
Overall Study
Death
|
2
|
1
|
Baseline Characteristics
Study of Effects of Sacubitril/Valsartan vs. Enalapril on Aortic Stiffness in Patients With Mild to Moderate HF With Reduced Ejection Fraction
Baseline characteristics by cohort
| Measure |
Enalapril (Double-Blind Phase)
n=233 Participants
minimum dose: 2.5mg, BID, oral, tablet. maximum dose: 10 mg, BID, oral tablet. All patients began on Dose Level 1 (2.5mg) and were titrated every two weeks to target Dose level 3 (10mg).
|
Sacubitril/Valsartan (Double-Blind Phase)
n=231 Participants
minimum dose: 24/26mg, BID, oral, tablet. maximum dose: 97/103mg, BID, oral, tablet. All patients began on Dose Level 1 (24/26mg) and were titrated every two weeks to target Dose level 3 (97/103mg).
|
Total
n=464 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
100 Participants
n=93 Participants
|
90 Participants
n=4 Participants
|
190 Participants
n=27 Participants
|
|
Age, Categorical
>=65 years
|
133 Participants
n=93 Participants
|
141 Participants
n=4 Participants
|
274 Participants
n=27 Participants
|
|
Sex: Female, Male
Female
|
48 Participants
n=93 Participants
|
61 Participants
n=4 Participants
|
109 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
185 Participants
n=93 Participants
|
170 Participants
n=4 Participants
|
355 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Caucasian (White)
|
175 articipants
n=93 Participants
|
166 articipants
n=4 Participants
|
341 articipants
n=27 Participants
|
|
Race/Ethnicity, Customized
Black
|
53 articipants
n=93 Participants
|
62 articipants
n=4 Participants
|
115 articipants
n=27 Participants
|
|
Race/Ethnicity, Customized
Asian
|
2 articipants
n=93 Participants
|
2 articipants
n=4 Participants
|
4 articipants
n=27 Participants
|
|
Race/Ethnicity, Customized
Native American
|
1 articipants
n=93 Participants
|
0 articipants
n=4 Participants
|
1 articipants
n=27 Participants
|
|
Race/Ethnicity, Customized
Other
|
0 articipants
n=93 Participants
|
1 articipants
n=4 Participants
|
1 articipants
n=27 Participants
|
|
Race/Ethnicity, Customized
Unknown
|
2 articipants
n=93 Participants
|
0 articipants
n=4 Participants
|
2 articipants
n=27 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 12Population: Full Analysis Set
Aortic characteristic impedance, Zc, is the ratio of the change in pressure (dP)produced by a given change in flow (dQ) in early systole, i.e., Zc = dP/dQ. Zc is related directly to aortic wall stiffness and inversely to lumen area.
Outcome measures
| Measure |
Enalapril (Double-Blind Phase)
n=233 Participants
minimum dose: 2.5mg, BID, oral, tablet. maximum dose: 10 mg, BID, oral tablet. All patients began on Dose Level 1 (2.5mg) and were titrated every two weeks to target Dose level 3 (10mg).
|
Sacubitril/Valsartan (Double-Blind Phase)
n=231 Participants
minimum dose: 24/26mg, BID, oral, tablet. maximum dose: 97/103mg, BID, oral, tablet. All patients began on Dose Level 1 (24/26mg) and were titrated every two weeks to target Dose level 3 (97/103mg).
|
|---|---|---|
|
Change From Baseline in Aortic Characteristic Impedance at Week 12
|
-0.7 dyne x sec/cm5
Standard Error 5.5
|
-2.9 dyne x sec/cm5
Standard Error 5.5
|
SECONDARY outcome
Timeframe: Pre-dose and 4 hours post dose at week 4Population: Full Analysis Set
Pearson correlation coefficients between changes from baseline in aortic characteristic impedance (dyne x sec/cm5) and biomarker levels such as BNP (pg/ML) during both trough and 4 hours post-dose at Week 4
Outcome measures
| Measure |
Enalapril (Double-Blind Phase)
n=233 Participants
minimum dose: 2.5mg, BID, oral, tablet. maximum dose: 10 mg, BID, oral tablet. All patients began on Dose Level 1 (2.5mg) and were titrated every two weeks to target Dose level 3 (10mg).
|
Sacubitril/Valsartan (Double-Blind Phase)
n=231 Participants
minimum dose: 24/26mg, BID, oral, tablet. maximum dose: 97/103mg, BID, oral, tablet. All patients began on Dose Level 1 (24/26mg) and were titrated every two weeks to target Dose level 3 (97/103mg).
|
|---|---|---|
|
Pearson Correlation Coefficient Between Change From Baseline in Aortic Characteristic Impedance and Biomarker Levels: B-type Natriuretic Peptide (BNP) During Both Trough and 4 Hours Post-dose at Week 4
Week 4 (post-dose)
|
-0.127 Pearson's Correlation
Interval -0.263 to 0.015
|
0.016 Pearson's Correlation
Interval -0.128 to 0.159
|
|
Pearson Correlation Coefficient Between Change From Baseline in Aortic Characteristic Impedance and Biomarker Levels: B-type Natriuretic Peptide (BNP) During Both Trough and 4 Hours Post-dose at Week 4
Week 4 (pre-dose)
|
0.022 Pearson's Correlation
Interval -0.113 to 0.156
|
0.070 Pearson's Correlation
Interval -0.069 to 0.207
|
SECONDARY outcome
Timeframe: pre-dose and 4 hours post dose at week 4Population: Full Analysis Set
Pearson correlation coefficient between changes from baseline in aortic characteristic impedance (dyne x sec/cm5) and biomarker levels such as U-cGMP/U-creatinine ratio (nmol/mmol) during both trough and 4 hours post-dose at Week 4
Outcome measures
| Measure |
Enalapril (Double-Blind Phase)
n=233 Participants
minimum dose: 2.5mg, BID, oral, tablet. maximum dose: 10 mg, BID, oral tablet. All patients began on Dose Level 1 (2.5mg) and were titrated every two weeks to target Dose level 3 (10mg).
|
Sacubitril/Valsartan (Double-Blind Phase)
n=231 Participants
minimum dose: 24/26mg, BID, oral, tablet. maximum dose: 97/103mg, BID, oral, tablet. All patients began on Dose Level 1 (24/26mg) and were titrated every two weeks to target Dose level 3 (97/103mg).
|
|---|---|---|
|
Pearson Correlation Coefficient Between Change From Baseline in Aortic Characteristic Impedance and Biomarker Levels: cGMP/U-creatinine During Both Trough and 4 Hours Post-dose at Week 4
Week 4 (pre-dose)
|
0.087 Pearson's correlation coefficient
Interval -0.049 to 0.22
|
0.098 Pearson's correlation coefficient
Interval -0.043 to 0.235
|
|
Pearson Correlation Coefficient Between Change From Baseline in Aortic Characteristic Impedance and Biomarker Levels: cGMP/U-creatinine During Both Trough and 4 Hours Post-dose at Week 4
Week 4 (post-dose)
|
0.110 Pearson's correlation coefficient
Interval -0.032 to 0.247
|
0.157 Pearson's correlation coefficient
Interval 0.014 to 0.294
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: Full Analysis Set
Change from baseline in N-terminal pro-brain natriuretic peptide (NT-proBNP)
Outcome measures
| Measure |
Enalapril (Double-Blind Phase)
n=233 Participants
minimum dose: 2.5mg, BID, oral, tablet. maximum dose: 10 mg, BID, oral tablet. All patients began on Dose Level 1 (2.5mg) and were titrated every two weeks to target Dose level 3 (10mg).
|
Sacubitril/Valsartan (Double-Blind Phase)
n=231 Participants
minimum dose: 24/26mg, BID, oral, tablet. maximum dose: 97/103mg, BID, oral, tablet. All patients began on Dose Level 1 (24/26mg) and were titrated every two weeks to target Dose level 3 (97/103mg).
|
|---|---|---|
|
Change From Baseline in N-terminal Pro-brain Natriuretic Peptide (NT-proBNP)
|
0.9500 pg/mL
Interval 0.8673 to 1.0406
|
0.6334 pg/mL
Interval 0.5778 to 0.6944
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: Full Analysis Set
Parameter measured by echocardiography.
Outcome measures
| Measure |
Enalapril (Double-Blind Phase)
n=233 Participants
minimum dose: 2.5mg, BID, oral, tablet. maximum dose: 10 mg, BID, oral tablet. All patients began on Dose Level 1 (2.5mg) and were titrated every two weeks to target Dose level 3 (10mg).
|
Sacubitril/Valsartan (Double-Blind Phase)
n=231 Participants
minimum dose: 24/26mg, BID, oral, tablet. maximum dose: 97/103mg, BID, oral, tablet. All patients began on Dose Level 1 (24/26mg) and were titrated every two weeks to target Dose level 3 (97/103mg).
|
|---|---|---|
|
Change From Baseline in Echocardiographic Measure: Global Longitudinal Strain
|
-0.21 Percentage
Standard Error 0.16
|
-0.34 Percentage
Standard Error 0.16
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: Full Analysis Set
Parameter measured by echocardiography
Outcome measures
| Measure |
Enalapril (Double-Blind Phase)
n=233 Participants
minimum dose: 2.5mg, BID, oral, tablet. maximum dose: 10 mg, BID, oral tablet. All patients began on Dose Level 1 (2.5mg) and were titrated every two weeks to target Dose level 3 (10mg).
|
Sacubitril/Valsartan (Double-Blind Phase)
n=231 Participants
minimum dose: 24/26mg, BID, oral, tablet. maximum dose: 97/103mg, BID, oral, tablet. All patients began on Dose Level 1 (24/26mg) and were titrated every two weeks to target Dose level 3 (97/103mg).
|
|---|---|---|
|
Change From Baseline in Echocardiographic Measure: Left Atrial Volume Index (LAVi)
|
0.63 mL/m2
Standard Error 0.44
|
-2.17 mL/m2
Standard Error 0.44
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: Full Analysis Set
Parameter measured by echocardiography
Outcome measures
| Measure |
Enalapril (Double-Blind Phase)
n=233 Participants
minimum dose: 2.5mg, BID, oral, tablet. maximum dose: 10 mg, BID, oral tablet. All patients began on Dose Level 1 (2.5mg) and were titrated every two weeks to target Dose level 3 (10mg).
|
Sacubitril/Valsartan (Double-Blind Phase)
n=231 Participants
minimum dose: 24/26mg, BID, oral, tablet. maximum dose: 97/103mg, BID, oral, tablet. All patients began on Dose Level 1 (24/26mg) and were titrated every two weeks to target Dose level 3 (97/103mg).
|
|---|---|---|
|
Change From Baseline in Echocardiographic Measure: Mitral Annular E' Velocity (Doppler Tissue Imaging)
|
-0.00 cm/sec
Standard Error 0.11
|
-0.03 cm/sec
Standard Error 0.11
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: Full Analysis Set
Parameter measured by echocardiography
Outcome measures
| Measure |
Enalapril (Double-Blind Phase)
n=233 Participants
minimum dose: 2.5mg, BID, oral, tablet. maximum dose: 10 mg, BID, oral tablet. All patients began on Dose Level 1 (2.5mg) and were titrated every two weeks to target Dose level 3 (10mg).
|
Sacubitril/Valsartan (Double-Blind Phase)
n=231 Participants
minimum dose: 24/26mg, BID, oral, tablet. maximum dose: 97/103mg, BID, oral, tablet. All patients began on Dose Level 1 (24/26mg) and were titrated every two weeks to target Dose level 3 (97/103mg).
|
|---|---|---|
|
Change From Basekine in Echocardiographic Measure: Mitral E/E'
|
0.32 Ratio
Standard Error 0.36
|
-1.43 Ratio
Standard Error 0.36
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: Full Analysis Set
Parameter measured by echocardiography
Outcome measures
| Measure |
Enalapril (Double-Blind Phase)
n=233 Participants
minimum dose: 2.5mg, BID, oral, tablet. maximum dose: 10 mg, BID, oral tablet. All patients began on Dose Level 1 (2.5mg) and were titrated every two weeks to target Dose level 3 (10mg).
|
Sacubitril/Valsartan (Double-Blind Phase)
n=231 Participants
minimum dose: 24/26mg, BID, oral, tablet. maximum dose: 97/103mg, BID, oral, tablet. All patients began on Dose Level 1 (24/26mg) and were titrated every two weeks to target Dose level 3 (97/103mg).
|
|---|---|---|
|
Change From Baseline in Echocardiographic Measure: Left Ventricular Ejection Fraction (LVEF)
|
1.30 Percentage
Standard Error 0.37
|
1.94 Percentage
Standard Error 0.38
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: Full Analysis Set
Parameter measured by echocardiography
Outcome measures
| Measure |
Enalapril (Double-Blind Phase)
n=233 Participants
minimum dose: 2.5mg, BID, oral, tablet. maximum dose: 10 mg, BID, oral tablet. All patients began on Dose Level 1 (2.5mg) and were titrated every two weeks to target Dose level 3 (10mg).
|
Sacubitril/Valsartan (Double-Blind Phase)
n=231 Participants
minimum dose: 24/26mg, BID, oral, tablet. maximum dose: 97/103mg, BID, oral, tablet. All patients began on Dose Level 1 (24/26mg) and were titrated every two weeks to target Dose level 3 (97/103mg).
|
|---|---|---|
|
Change From Baseline in Echocardiographic Measure: Ventricular-vascular Coupling (Ea/Ees)
|
0.03 Ea/Ees Ratio
Standard Error 0.01
|
0.02 Ea/Ees Ratio
Standard Error 0.02
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: Full Analysis Set
Parameter measured by echocardiography
Outcome measures
| Measure |
Enalapril (Double-Blind Phase)
n=233 Participants
minimum dose: 2.5mg, BID, oral, tablet. maximum dose: 10 mg, BID, oral tablet. All patients began on Dose Level 1 (2.5mg) and were titrated every two weeks to target Dose level 3 (10mg).
|
Sacubitril/Valsartan (Double-Blind Phase)
n=231 Participants
minimum dose: 24/26mg, BID, oral, tablet. maximum dose: 97/103mg, BID, oral, tablet. All patients began on Dose Level 1 (24/26mg) and were titrated every two weeks to target Dose level 3 (97/103mg).
|
|---|---|---|
|
Change From Baseline in Echocardiographic Measure: Left Ventricular End Systolic Volume Index (LVESVi)
|
-3.28 mL/m2
Standard Error 0.55
|
-4.86 mL/m2
Standard Error 0.56
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: Full Analysis Set
Parameter measured by echocardiography
Outcome measures
| Measure |
Enalapril (Double-Blind Phase)
n=233 Participants
minimum dose: 2.5mg, BID, oral, tablet. maximum dose: 10 mg, BID, oral tablet. All patients began on Dose Level 1 (2.5mg) and were titrated every two weeks to target Dose level 3 (10mg).
|
Sacubitril/Valsartan (Double-Blind Phase)
n=231 Participants
minimum dose: 24/26mg, BID, oral, tablet. maximum dose: 97/103mg, BID, oral, tablet. All patients began on Dose Level 1 (24/26mg) and were titrated every two weeks to target Dose level 3 (97/103mg).
|
|---|---|---|
|
Change From Baseline in Echocardiographic Measure: Left Ventricular End Diastolic Volume Index (LVEDVi)
|
-3.18 mL/m2
Standard Error 0.61
|
-5.15 mL/m2
Standard Error 0.62
|
Adverse Events
Double Blind Phase Enalapril
Serious events: 21 serious events
Other events: 32 other events
Deaths: 1 deaths
Double Blind Phase Sacubitril/Valsartan
Serious events: 17 serious events
Other events: 43 other events
Deaths: 1 deaths
Open-Label Phase Sacubitril/Valsartan
Serious events: 40 serious events
Other events: 42 other events
Deaths: 5 deaths
Serious adverse events
| Measure |
Double Blind Phase Enalapril
n=233 participants at risk
Minimum dose: 2.5mg, BID, oral, tablet. Maximum dose: 10 mg, BID, oral tablet. All patients began on Dose Level 1 (2.5mg) and were titrated every two weeks to target Dose level 3 (10mg).
|
Double Blind Phase Sacubitril/Valsartan
n=231 participants at risk
Minimum dose: 24/26mg, BID, oral, tablet. Maximum dose:
97/103mg, BID, oral, tablet. All patients began on Dose Level 1 (24/26mg) and were titrated every two weeks to target Dose level 3 (97/103mg).
|
Open-Label Phase Sacubitril/Valsartan
n=454 participants at risk
LCZ696 tablets were provided for the 12-week open label extension.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.43%
1/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Cardiac disorders
Acute coronary syndrome
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.43%
1/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Cardiac disorders
Acute left ventricular failure
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.43%
1/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Cardiac disorders
Acute myocardial infarction
|
1.3%
3/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.44%
2/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.66%
3/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Cardiac disorders
Angina unstable
|
0.43%
1/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.87%
2/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Cardiac disorders
Atrioventricular block complete
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.22%
1/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Cardiac disorders
Bradycardia
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.44%
2/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Cardiac disorders
Cardiac arrest
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.44%
2/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Cardiac disorders
Cardiac failure
|
1.3%
3/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.43%
1/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.44%
2/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Cardiac disorders
Cardiac failure chronic
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.66%
3/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Cardiac disorders
Cardiac failure congestive
|
0.86%
2/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.43%
1/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.66%
3/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Cardiac disorders
Cardiomegaly
|
0.43%
1/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Cardiac disorders
Cardiovascular disorder
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.22%
1/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Cardiac disorders
Coronary artery disease
|
0.43%
1/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.22%
1/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Cardiac disorders
Left ventricular failure
|
0.43%
1/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.87%
2/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.44%
2/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.43%
1/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Cardiac disorders
Ventricular fibrillation
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.43%
1/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.22%
1/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Cardiac disorders
Ventricular tachycardia
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.43%
1/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.22%
1/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.22%
1/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.22%
1/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
General disorders
Multiple organ dysfunction syndrome
|
0.43%
1/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
General disorders
Necrosis
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.22%
1/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.22%
1/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
General disorders
Oedema peripheral
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.22%
1/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
General disorders
Swelling
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.22%
1/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.43%
1/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.43%
1/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Infections and infestations
Abdominal wall abscess
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.22%
1/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Infections and infestations
Bronchitis
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.43%
1/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Infections and infestations
Cystitis
|
0.43%
1/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Infections and infestations
Device related sepsis
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.43%
1/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.43%
1/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Infections and infestations
Osteomyelitis
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.22%
1/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Infections and infestations
Periorbital cellulitis
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.22%
1/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Infections and infestations
Pneumonia
|
1.3%
3/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.43%
1/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.44%
2/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Infections and infestations
Sepsis
|
0.86%
2/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.22%
1/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Infections and infestations
Urinary tract infection
|
0.43%
1/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.22%
1/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Infections and infestations
Urosepsis
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.22%
1/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Injury, poisoning and procedural complications
Femoral neck fracture
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.22%
1/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.22%
1/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.22%
1/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Investigations
Troponin increased
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.43%
1/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.43%
1/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.43%
1/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.43%
1/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.22%
1/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.87%
2/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.22%
1/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.43%
1/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.43%
1/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatic cancer metastatic
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.22%
1/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Myelodysplastic syndrome
|
0.43%
1/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Plasma cell myeloma
|
0.43%
1/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of lung
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.22%
1/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Nervous system disorders
Carotid artery disease
|
0.43%
1/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Nervous system disorders
Carotid artery stenosis
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.22%
1/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.22%
1/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Nervous system disorders
Ischaemic stroke
|
0.43%
1/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Nervous system disorders
Syncope
|
0.86%
2/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.43%
1/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.22%
1/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Product Issues
Device failure
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.22%
1/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Product Issues
Device malfunction
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.22%
1/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Renal and urinary disorders
Chronic kidney disease
|
0.43%
1/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.43%
1/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema
|
0.86%
2/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.43%
1/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.87%
2/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.22%
1/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.44%
2/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.22%
1/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.86%
2/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.44%
2/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.43%
1/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Vascular disorders
Dry gangrene
|
0.43%
1/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Vascular disorders
Hypotension
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.22%
1/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Vascular disorders
Lymphoedema
|
0.00%
0/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.00%
0/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
0.22%
1/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
Other adverse events
| Measure |
Double Blind Phase Enalapril
n=233 participants at risk
Minimum dose: 2.5mg, BID, oral, tablet. Maximum dose: 10 mg, BID, oral tablet. All patients began on Dose Level 1 (2.5mg) and were titrated every two weeks to target Dose level 3 (10mg).
|
Double Blind Phase Sacubitril/Valsartan
n=231 participants at risk
Minimum dose: 24/26mg, BID, oral, tablet. Maximum dose:
97/103mg, BID, oral, tablet. All patients began on Dose Level 1 (24/26mg) and were titrated every two weeks to target Dose level 3 (97/103mg).
|
Open-Label Phase Sacubitril/Valsartan
n=454 participants at risk
LCZ696 tablets were provided for the 12-week open label extension.
|
|---|---|---|---|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
5.6%
13/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
7.4%
17/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
2.6%
12/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Nervous system disorders
Dizziness
|
3.9%
9/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
5.6%
13/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
3.3%
15/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
|
Vascular disorders
Hypotension
|
5.6%
13/233 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
8.2%
19/231 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
3.5%
16/454 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 2.5 years.
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
- Publication restrictions are in place
Restriction type: OTHER