Trial Outcomes & Findings for Safety and Efficacy of Aliskiren in Post Myocardial Infarction Patients (ASPIRE) (NCT NCT00414609)

Last Updated: 2012-07-13

Results Overview

Change from baseline to end of study in left ventricular end systolic volume (LVESV) as measured by echocardiography. LVESV is a measurement of the volume of blood in the heart's left ventricular chamber at the end of the heart's contraction. This measurement was made by the echocardiography lab. LVESV values between 22 to 58 mL for men and 19-49 mL for women are considered normal. Baseline LVESV was a covariate.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

820 participants

Primary outcome timeframe

Baseline and final visit (after 26 to 36 weeks of treatment)

Results posted on

2012-07-13

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo_Core Placebo for 36 weeks once daily in the morning	Aliskiren_Core Aliskiren ascending doses: 75 mg tablet for 1st week, 150 mg for 2nd week, 300 mg for the next 34 weeks orally once daily in the morning.	Aliskiren_Extension Patients from both the arms of the core study who completed core study and signed informed consent form were included in this arm of extension study. Patients received 150 mg aliskiren tablet orally once a day for two weeks. Patients were then up-titrated to 300 mg aliskiren orally once a day at the discretion of the principal investigator based on their clinical condition for the duration of the study.
Core Study STARTED	397	423	0
Core Study Received Study Drug	397	422	0
Core Study Echocardiogram Evaluable Set	330	343	0
Core Study COMPLETED	363	378	0
Core Study NOT COMPLETED	34	45	0
Extension Study STARTED	0	0	422
Extension Study Echocardiogram (ECHO) Analysis Set	0	0	400
Extension Study COMPLETED	0	0	365
Extension Study NOT COMPLETED	0	0	57

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo_Core Placebo for 36 weeks once daily in the morning	Aliskiren_Core Aliskiren ascending doses: 75 mg tablet for 1st week, 150 mg for 2nd week, 300 mg for the next 34 weeks orally once daily in the morning.	Aliskiren_Extension Patients from both the arms of the core study who completed core study and signed informed consent form were included in this arm of extension study. Patients received 150 mg aliskiren tablet orally once a day for two weeks. Patients were then up-titrated to 300 mg aliskiren orally once a day at the discretion of the principal investigator based on their clinical condition for the duration of the study.
Core Study Adverse Event	9	11	0
Core Study Abnormal laboratory values	0	1	0
Core Study Abnormal test procedure results	1	1	0
Core Study Protocol deviation	0	1	0
Core Study Patient withdrew consent	10	11	0
Core Study Lost to Follow-up	7	4	0
Core Study Administrative problems	0	2	0
Core Study Death	7	14	0
Extension Study Adverse Event	0	0	14
Extension Study Unsatisfactory therapeutic effect	0	0	2
Extension Study Withdrawal by Subject	0	0	13
Extension Study Lost to Follow-up	0	0	10
Extension Study Administrative problems	0	0	1
Extension Study Death	0	0	17

Baseline Characteristics

Safety and Efficacy of Aliskiren in Post Myocardial Infarction Patients (ASPIRE)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=397 Participants Placebo for 36 weeks once daily in the morning	Aliskiren n=423 Participants Aliskiren ascending doses: 75 mg tablet for 1st week, 150 mg for 2nd week, 300 mg for the next 34 weeks orally once daily in the morning.	Total n=820 Participants Total of all reporting groups
Age Continuous	59.4 years STANDARD_DEVIATION 11.67 • n=5 Participants	60.7 years STANDARD_DEVIATION 11.63 • n=7 Participants	60.0 years STANDARD_DEVIATION 11.66 • n=5 Participants
Age, Customized < 65 years	261 Participants n=5 Participants	254 Participants n=7 Participants	515 Participants n=5 Participants
Age, Customized ≥ 65 years and < 75 years	93 Participants n=5 Participants	114 Participants n=7 Participants	207 Participants n=5 Participants
Age, Customized ≥ 75 years	43 Participants n=5 Participants	55 Participants n=7 Participants	98 Participants n=5 Participants
Sex: Female, Male Female	61 Participants n=5 Participants	80 Participants n=7 Participants	141 Participants n=5 Participants
Sex: Female, Male Male	336 Participants n=5 Participants	343 Participants n=7 Participants	679 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and final visit (after 26 to 36 weeks of treatment)

Population: Echocardiogram evaluable set (patients who had acceptable echocardiogram measurements both at baseline and at post-baseline after receiving at least 26 weeks of treatment)

Outcome measures

Outcome measures
Measure	Placebo_Core n=329 Participants Placebo for 36 weeks once daily in the morning	Aliskiren_Core n=343 Participants Aliskiren ascending doses: 75 mg tablet for 1st week, 150 mg for 2nd week, 300 mg for the next 34 weeks orally once daily in the morning.
Core Study: Change From Baseline in Left Ventricular End Systolic Volume (LVESV) as Measured by Echocardiography at End of Study.	-3.14 mL Standard Error 1.01	-4.13 mL Standard Error 0.97

PRIMARY outcome

Timeframe: Extension study (24 weeks)

Population: Extension Population (considered as Safety population) consisting of all enrolled patients who received at least one dose of study medication in the extension study.

AEs are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.

Outcome measures

Outcome measures
Measure	Placebo_Core n=422 Participants Placebo for 36 weeks once daily in the morning	Aliskiren_Core Aliskiren ascending doses: 75 mg tablet for 1st week, 150 mg for 2nd week, 300 mg for the next 34 weeks orally once daily in the morning.
Extension Study: Percentage of Participants With Deaths, Serious Adverse Events (SAEs), Discontinuation for Adverse Events (AEs) and Discontinuations for Abnormal Lab Values Deaths	4.0 Percentage of participants	—
Extension Study: Percentage of Participants With Deaths, Serious Adverse Events (SAEs), Discontinuation for Adverse Events (AEs) and Discontinuations for Abnormal Lab Values SAEs	29.9 Percentage of participants	—
Extension Study: Percentage of Participants With Deaths, Serious Adverse Events (SAEs), Discontinuation for Adverse Events (AEs) and Discontinuations for Abnormal Lab Values AE discontinuations	7.1 Percentage of participants	—
Extension Study: Percentage of Participants With Deaths, Serious Adverse Events (SAEs), Discontinuation for Adverse Events (AEs) and Discontinuations for Abnormal Lab Values Drug-related AE discontinuations	2.4 Percentage of participants	—
Extension Study: Percentage of Participants With Deaths, Serious Adverse Events (SAEs), Discontinuation for Adverse Events (AEs) and Discontinuations for Abnormal Lab Values SAE discontinuations	5.2 Percentage of participants	—
Extension Study: Percentage of Participants With Deaths, Serious Adverse Events (SAEs), Discontinuation for Adverse Events (AEs) and Discontinuations for Abnormal Lab Values Discontinuations for abnormal lab values	0 Percentage of participants	—

SECONDARY outcome

Timeframe: LVEF was measured at baseline and at final visit (after 26 to 36 weeks of treatment). Other endpoint components were assessed from randomization until the end of the study (week 36).

Population: Full Analysis Set (FAS) - All randomized patients who either (a) received study drug or (b) did not receive study drug but were not disqualified from randomization.

Composite outcome 1 included: Cardiovascular (CV) Death, hospitalization for heart failure (HF), or absolute reduction in Left Ventricular Ejection Fraction (LVEF) greater than 6%. Composite outcome 2 included: CV Death, hospitalization for HF, recurrent Myocardial Infarction, Stroke, or Resuscitated Sudden Death. LVEF was measured at baseline and final visit. All other events were adjudicated by a blinded external committee. Each composite endpoint analysis was based on (a) the percent of patients with that endpoint and (b) days in study to 1st event (or last exposure if no event occurred).

Outcome measures

Outcome measures
Measure	Placebo_Core n=397 Participants Placebo for 36 weeks once daily in the morning	Aliskiren_Core n=423 Participants Aliskiren ascending doses: 75 mg tablet for 1st week, 150 mg for 2nd week, 300 mg for the next 34 weeks orally once daily in the morning.
Core Study: Time to First Occurrence for the Composite Endpoints of Echocardiogram and Adjudicated Outcomes Composite Outcome 2	8.6 Percentage of participants	9.2 Percentage of participants
Core Study: Time to First Occurrence for the Composite Endpoints of Echocardiogram and Adjudicated Outcomes Composite Outcome 1	6.0 Percentage of participants	6.9 Percentage of participants

SECONDARY outcome

Timeframe: Baseline and final visit (after 26 to 36 weeks of treatment)

Population: Echocardiogram evaluable set: Patients who had acceptable echocardiogram measurements both at baseline and at post-baseline after receiving at least 26 weeks of treatment.

Change from baseline to end of study in left ventricular end diastolic volume (LVEDV) as measured by echocardiography. (LVEDV) is a measurement of the volume of blood in the heart's left ventricular chamber at the beginning of the chamber's filling with blood. This measurement was made by the echocardiography lab. LVEDV values between 67 to 155 mL for men and 56 to 104 mL for women are considered normal. Baseline LVEDV was a covariate.

Outcome measures

Outcome measures
Measure	Placebo_Core n=329 Participants Placebo for 36 weeks once daily in the morning	Aliskiren_Core n=343 Participants Aliskiren ascending doses: 75 mg tablet for 1st week, 150 mg for 2nd week, 300 mg for the next 34 weeks orally once daily in the morning.
Core Study: Change From Baseline in Left Ventricular End Diastolic Volume (LVEDV)	-1.37 mL Standard Error 1.19	-3.08 mL Standard Error 1.15

SECONDARY outcome

Timeframe: Baseline and final visit (after 26 to 36 weeks of treatment )

Population: Echocardiogram evaluable set: Patients who had acceptable echocardiogram measurements both at baseline and at post-baseline after receiving at least 26 weeks of treatment.

Change from baseline to end of study in left ventricular ejection fraction (LVEF) (%) as measured by echocardiography. LVEF is the fraction of blood (in percent) pumped out of the heart's left ventricular chamber with each heart beat, and is a measure of cardiac output for the heart. This measurement was made by the echocardiography lab. Ejection fraction percentages \> 55% are considered normal. Baseline LVEF was a covariate.

Outcome measures

Outcome measures
Measure	Placebo_Core n=329 Participants Placebo for 36 weeks once daily in the morning	Aliskiren_Core n=343 Participants Aliskiren ascending doses: 75 mg tablet for 1st week, 150 mg for 2nd week, 300 mg for the next 34 weeks orally once daily in the morning.
Core Study: Change From Baseline in Left Ventricular Ejection Fraction (LVEF)	2.12 percent of blood pumped from LV chamber Standard Error 0.27	2.24 percent of blood pumped from LV chamber Standard Error 0.26

SECONDARY outcome

Timeframe: Baseline and final visit (after 26 to 36 weeks of treatment)

Population: Echocardiogram evaluable set: Patients who had acceptable echocardiogram measurements both at baseline and at post-baseline after receiving at least 26 weeks of treatment.

Change from baseline to end of study in infarction segment length (ISL) (%) as measured by echocardiography. This is the length of the myocardial infarction segment as a percentage of the total cavity perimeter length as calculated by the echocardiography lab. Baseline ISL was a covariate.

Outcome measures

Outcome measures
Measure	Placebo_Core n=330 Participants Placebo for 36 weeks once daily in the morning	Aliskiren_Core n=343 Participants Aliskiren ascending doses: 75 mg tablet for 1st week, 150 mg for 2nd week, 300 mg for the next 34 weeks orally once daily in the morning.
Core Study: Change From Baseline to End of Study in Infarction Segment Length (ISL) as Measured by Echocardiography	-4.30 percent of total cavity perimeter length Standard Error 0.53	-5.04 percent of total cavity perimeter length Standard Error 0.51

SECONDARY outcome

Timeframe: Baseline and final visit (after 26 to 36 weeks of treatment)

Population: Echocardiogram evaluable set: Patients who had acceptable echocardiogram measurements both at baseline and at post-baseline after receiving at least 26 weeks of treatment.

Change from baseline to end of study in Wall Motion Score (WMS) as measured by echocardiography. WMS was obtained by examining multiple segments of the left ventricle and assigning each segment a score based on myocardial thickening: 1 for normal, 2 for hypokinetic; 3 for akinetic; and 4 for dyskinetic. The WMS was obtained as the average score for the segments visualized and was calculated by the echocardiography lab. Possible values range from 1 to 5. Higher scores are considered worse. Baseline WMS was a covariate.

Outcome measures

Outcome measures
Measure	Placebo_Core n=327 Participants Placebo for 36 weeks once daily in the morning	Aliskiren_Core n=340 Participants Aliskiren ascending doses: 75 mg tablet for 1st week, 150 mg for 2nd week, 300 mg for the next 34 weeks orally once daily in the morning.
Core Study: Change From Baseline to End of Study in Wall Motion Score (WMS) as Measured by Echocardiography	-0.08 Scores on a scale Standard Error 0.01	-0.10 Scores on a scale Standard Error 0.01

SECONDARY outcome

Timeframe: Baseline(extension study), Month 12 (extension study)

Population: Echocardiogram Analysis Set consisting of all patients in the extension population who had acceptable ECHO measurements at extension baseline and Month 12.

Change from baseline to Month 12 in left ventricular end systolic volume (LVESV) as measured by echocardiography. LVESV is a measurement of the volume of blood in the heart's left ventricular chamber at the end of the heart's contraction. This measurement was made by the echocardiography lab. LVESV values between 22 to 58 mL for men and 19-49 mL for women are considered normal.

Outcome measures

Outcome measures
Measure	Placebo_Core n=302 Participants Placebo for 36 weeks once daily in the morning	Aliskiren_Core Aliskiren ascending doses: 75 mg tablet for 1st week, 150 mg for 2nd week, 300 mg for the next 34 weeks orally once daily in the morning.
Extension Study: Change From Baseline in Left Ventricular End Systolic Volume (LVESV) at Month 12	-6.2 Milliliter (mL) Standard Deviation 14.32	—

SECONDARY outcome

Timeframe: Baseline (extension study), Month 12 (extension study)

Population: Echocardiogram Analysis Set consisting of all patients in the extension population who had acceptable ECHO measurements at extension baseline and Month 12.

Change from baseline to Month 12 in left ventricular end diastolic volume (LVEDV) as measured by echocardiography. LVEDV is a measurement of the volume of blood in the heart's left ventricular chamber at the beginning of the chamber's filling with blood. This measurement was made by the echocardiography lab. LVEDV values between 67 to 155 mL for men and 56 to 104 mL for women are considered normal.

Outcome measures

Outcome measures
Measure	Placebo_Core n=302 Participants Placebo for 36 weeks once daily in the morning	Aliskiren_Core Aliskiren ascending doses: 75 mg tablet for 1st week, 150 mg for 2nd week, 300 mg for the next 34 weeks orally once daily in the morning.
Extension Study: Change From Baseline in Left Ventricular End Diastolic Volume (LVEDV) at Month 12	6.0 Milliliter (mL) Standard Deviation 18.34	—

SECONDARY outcome

Timeframe: Baseline(extension study), Month 12 (extension study)

Population: Echocardiogram Analysis Set consisting of all patients in the extension population who had acceptable ECHO measurements at extension baseline and Month 12.

Change from baseline to Month 12 in left ventricular ejection fraction (LVEF) (%) as measured by echocardiography. LVEF is the fraction of blood (in percent) pumped out of the heart's left ventricular chamber with each heart beat, and is a measure of cardiac output for the heart. This measurement was made by the echocardiography lab. Ejection fraction percentages \> 55% are considered normal.

Outcome measures

Outcome measures
Measure	Placebo_Core n=302 Participants Placebo for 36 weeks once daily in the morning	Aliskiren_Core Aliskiren ascending doses: 75 mg tablet for 1st week, 150 mg for 2nd week, 300 mg for the next 34 weeks orally once daily in the morning.
Extension Study: Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Month 12	7.4 percent of blood pumped from LV chamber Standard Deviation 6.46	—

SECONDARY outcome

Timeframe: Baseline (Day 0 Extension study), Week 2, Months 1, 3, 6, 9,16, 20, 24

Population: Extension population (considered as Safety population) consisted of all enrolled patients who received at least one dose of study medication in the extension study. "n" in each of the categories is the number of participants with data available at the given time-point.

Orthostatic blood pressure change is defined as a decrease of at least 20 mmHg in systolic blood pressure or a decrease of at least 10 mmHg in diastolic blood pressure when a patient moves from a sitting position to a standing position. A patient could show orthostatic blood pressure change at more than one visit. End of study is Month 24 or early discontinuation.

Outcome measures

Outcome measures
Measure	Placebo_Core n=422 Participants Placebo for 36 weeks once daily in the morning	Aliskiren_Core Aliskiren ascending doses: 75 mg tablet for 1st week, 150 mg for 2nd week, 300 mg for the next 34 weeks orally once daily in the morning.
Extension Study: Percentage of Participants With Orthostatic Blood Pressure Change Month 1 (n=418)	4.1 Percentage of Participants	—
Extension Study: Percentage of Participants With Orthostatic Blood Pressure Change Baseline (n=420)	2.4 Percentage of Participants	—
Extension Study: Percentage of Participants With Orthostatic Blood Pressure Change Week 2 (n=416)	4.6 Percentage of Participants	—
Extension Study: Percentage of Participants With Orthostatic Blood Pressure Change Month 3 (n=410)	4.6 Percentage of Participants	—
Extension Study: Percentage of Participants With Orthostatic Blood Pressure Change Month 6 (n=400)	3.3 Percentage of Participants	—
Extension Study: Percentage of Participants With Orthostatic Blood Pressure Change Month 9 (n=397)	4.3 Percentage of Participants	—
Extension Study: Percentage of Participants With Orthostatic Blood Pressure Change Month 12 (n=385)	3.6 Percentage of Participants	—
Extension Study: Percentage of Participants With Orthostatic Blood Pressure Change Month 16 (n=383)	5.0 Percentage of Participants	—
Extension Study: Percentage of Participants With Orthostatic Blood Pressure Change Month 20 (n=350)	4.3 Percentage of Participants	—
Extension Study: Percentage of Participants With Orthostatic Blood Pressure Change Month 24 (n=360)	3.6 Percentage of Participants	—
Extension Study: Percentage of Participants With Orthostatic Blood Pressure Change End of Study (n=422)	3.8 Percentage of Participants	—
Extension Study: Percentage of Participants With Orthostatic Blood Pressure Change Any post-baseline visit (n=422)	23.5 Percentage of Participants	—

SECONDARY outcome

Timeframe: 24 Months

Fasting blood samples were collected throughout the study and were analyzed at a central laboratory. Percentage of participants with the following clinically significant laboratory values are reported: Potassium \<3.5 mmol/L; Low value (Normal reference range: 3.5- 5.3) Potassium \>5.5 mmol/L and Potassium \>6.0 mmol/L; High values (Normal reference range: 3.5-5.3) Creatinine \>176.8 μmol/L; High value (Normal reference range= Male: 62- 106 and Female 44- 80) Blood Urea Nitrogen (BUN) \>14.28; High value (Normal reference range: 2.1- 8.9)

Outcome measures

Outcome measures
Measure	Placebo_Core n=422 Participants Placebo for 36 weeks once daily in the morning	Aliskiren_Core Aliskiren ascending doses: 75 mg tablet for 1st week, 150 mg for 2nd week, 300 mg for the next 34 weeks orally once daily in the morning.
Extension Study: Percentage of Participants With Specified Criteria in Selected Labs by Laboratory Parameter Potassium <3.5 mmol/L (n=409)	1.5 Percentage of participants	—
Extension Study: Percentage of Participants With Specified Criteria in Selected Labs by Laboratory Parameter Potassium >5.5 mmol/L (n=409)	11.2 Percentage of participants	—
Extension Study: Percentage of Participants With Specified Criteria in Selected Labs by Laboratory Parameter Potassium ≥6.0 mmol/L (n=409)	4.6 Percentage of participants	—
Extension Study: Percentage of Participants With Specified Criteria in Selected Labs by Laboratory Parameter Creatinine >176.8 μmol/L (n=412)	4.4 Percentage of participants	—
Extension Study: Percentage of Participants With Specified Criteria in Selected Labs by Laboratory Parameter BUN >14.28 mmol/L (n=412)	8.7 Percentage of participants	—

Adverse Events

Placebo_core

Serious events: 92 serious events

Other events: 118 other events

Deaths: 0 deaths

Aliskiren_core

Serious events: 107 serious events

Other events: 161 other events

Deaths: 0 deaths

Aliskiren_extension

Serious events: 126 serious events

Other events: 123 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo_core n=397 participants at risk Placebo for 36 weeks once daily in the morning	Aliskiren_core n=422 participants at risk Aliskiren ascending doses: 75 mg tablet for 1st week, 150 mg for 2nd week, 300 mg for the next 34 weeks orally once daily in the morning.	Aliskiren_extension n=422 participants at risk Patients from both the arms of the core study who completed core study and signed informed consent form were included in this arm of extension study. Patients received 150 mg aliskiren tablet orally once a day for two weeks. Patients were then up-titrated to 300 mg aliskiren orally once a day at the discretion of the principal investigator based on their clinical condition for the duration of the study.
Cardiac disorders Angina pectoris	5.8% 23/397 Core Safety population: All patients that received at least one dose of study drug. Extension Safety Population: All enrolled patients who received at least one dose of study medication in the extension study. Extension study enrolled patients from both the arms of core who complete core study and signed an informed consent form.	5.7% 24/422 Core Safety population: All patients that received at least one dose of study drug. Extension Safety Population: All enrolled patients who received at least one dose of study medication in the extension study. Extension study enrolled patients from both the arms of core who complete core study and signed an informed consent form.	4.5% 19/422 Core Safety population: All patients that received at least one dose of study drug. Extension Safety Population: All enrolled patients who received at least one dose of study medication in the extension study. Extension study enrolled patients from both the arms of core who complete core study and signed an informed consent form.
Cardiac disorders Cardiac failure	5.3% 21/397 Core Safety population: All patients that received at least one dose of study drug. Extension Safety Population: All enrolled patients who received at least one dose of study medication in the extension study. Extension study enrolled patients from both the arms of core who complete core study and signed an informed consent form.	7.1% 30/422 Core Safety population: All patients that received at least one dose of study drug. Extension Safety Population: All enrolled patients who received at least one dose of study medication in the extension study. Extension study enrolled patients from both the arms of core who complete core study and signed an informed consent form.	1.7% 7/422 Core Safety population: All patients that received at least one dose of study drug. Extension Safety Population: All enrolled patients who received at least one dose of study medication in the extension study. Extension study enrolled patients from both the arms of core who complete core study and signed an informed consent form.
General disorders Non-cardiac chest pain	3.8% 15/397 Core Safety population: All patients that received at least one dose of study drug. Extension Safety Population: All enrolled patients who received at least one dose of study medication in the extension study. Extension study enrolled patients from both the arms of core who complete core study and signed an informed consent form.	5.2% 22/422 Core Safety population: All patients that received at least one dose of study drug. Extension Safety Population: All enrolled patients who received at least one dose of study medication in the extension study. Extension study enrolled patients from both the arms of core who complete core study and signed an informed consent form.	4.5% 19/422 Core Safety population: All patients that received at least one dose of study drug. Extension Safety Population: All enrolled patients who received at least one dose of study medication in the extension study. Extension study enrolled patients from both the arms of core who complete core study and signed an informed consent form.
Infections and infestations Nasopharyngitis	6.0% 24/397 Core Safety population: All patients that received at least one dose of study drug. Extension Safety Population: All enrolled patients who received at least one dose of study medication in the extension study. Extension study enrolled patients from both the arms of core who complete core study and signed an informed consent form.	5.5% 23/422 Core Safety population: All patients that received at least one dose of study drug. Extension Safety Population: All enrolled patients who received at least one dose of study medication in the extension study. Extension study enrolled patients from both the arms of core who complete core study and signed an informed consent form.	6.6% 28/422 Core Safety population: All patients that received at least one dose of study drug. Extension Safety Population: All enrolled patients who received at least one dose of study medication in the extension study. Extension study enrolled patients from both the arms of core who complete core study and signed an informed consent form.
Metabolism and nutrition disorders Hyperkalaemia	1.3% 5/397 Core Safety population: All patients that received at least one dose of study drug. Extension Safety Population: All enrolled patients who received at least one dose of study medication in the extension study. Extension study enrolled patients from both the arms of core who complete core study and signed an informed consent form.	5.2% 22/422 Core Safety population: All patients that received at least one dose of study drug. Extension Safety Population: All enrolled patients who received at least one dose of study medication in the extension study. Extension study enrolled patients from both the arms of core who complete core study and signed an informed consent form.	2.8% 12/422 Core Safety population: All patients that received at least one dose of study drug. Extension Safety Population: All enrolled patients who received at least one dose of study medication in the extension study. Extension study enrolled patients from both the arms of core who complete core study and signed an informed consent form.
Nervous system disorders Dizziness	3.8% 15/397 Core Safety population: All patients that received at least one dose of study drug. Extension Safety Population: All enrolled patients who received at least one dose of study medication in the extension study. Extension study enrolled patients from both the arms of core who complete core study and signed an informed consent form.	6.4% 27/422 Core Safety population: All patients that received at least one dose of study drug. Extension Safety Population: All enrolled patients who received at least one dose of study medication in the extension study. Extension study enrolled patients from both the arms of core who complete core study and signed an informed consent form.	5.7% 24/422 Core Safety population: All patients that received at least one dose of study drug. Extension Safety Population: All enrolled patients who received at least one dose of study medication in the extension study. Extension study enrolled patients from both the arms of core who complete core study and signed an informed consent form.
Respiratory, thoracic and mediastinal disorders Cough	7.1% 28/397 Core Safety population: All patients that received at least one dose of study drug. Extension Safety Population: All enrolled patients who received at least one dose of study medication in the extension study. Extension study enrolled patients from both the arms of core who complete core study and signed an informed consent form.	6.4% 27/422 Core Safety population: All patients that received at least one dose of study drug. Extension Safety Population: All enrolled patients who received at least one dose of study medication in the extension study. Extension study enrolled patients from both the arms of core who complete core study and signed an informed consent form.	3.6% 15/422 Core Safety population: All patients that received at least one dose of study drug. Extension Safety Population: All enrolled patients who received at least one dose of study medication in the extension study. Extension study enrolled patients from both the arms of core who complete core study and signed an informed consent form.
Vascular disorders Hypotension	4.0% 16/397 Core Safety population: All patients that received at least one dose of study drug. Extension Safety Population: All enrolled patients who received at least one dose of study medication in the extension study. Extension study enrolled patients from both the arms of core who complete core study and signed an informed consent form.	8.5% 36/422 Core Safety population: All patients that received at least one dose of study drug. Extension Safety Population: All enrolled patients who received at least one dose of study medication in the extension study. Extension study enrolled patients from both the arms of core who complete core study and signed an informed consent form.	9.7% 41/422 Core Safety population: All patients that received at least one dose of study drug. Extension Safety Population: All enrolled patients who received at least one dose of study medication in the extension study. Extension study enrolled patients from both the arms of core who complete core study and signed an informed consent form.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

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 (i.e., data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER