Trial Outcomes & Findings for A Randomized Controlled Trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly People (NCT NCT01259297)

Last Updated: 2014-04-08

Results Overview

The composite CV endpoint is based on the following first adjudicated events: CV death, non-fatal MI,non-fatal stroke, significant heart failure

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

2336 participants

Primary outcome timeframe

End of study (209 days (median))

Results posted on

2014-04-08

Participant Flow

Participant milestones

Participant milestones
Measure	Aliskiren + Hydrochlorothiazide (HCTZ) In run-in period (4-5 weeks) , patients on CCB background therapy and approximately 50% of patients on neither thiazide nor CCB background therapy: received hydrochlorothiazide 12.5/25 mg and Aliskiren 150/300 mg daily in a titrated manner as per protocol. In double blind period, all patients who successfully completed run-in with HCTZ plus aliskiren were randomized equally to the 4 arms of the HCTZ add-on stratum. Patients randomized to this arm received Aliskiren 300 mg + HCTZ 25 mg once daily.	Aliskiren + Placebo for HCTZ In double blind period, all patients who successfully completed run-in with HCTZ plus Aliskiren were randomized equally to the 4 arms of the HCTZ add-on stratum. In double blind period, randomized patients to this arm received Aliskiren 300 mg + placebo for HCTZ 25 mg once daily	Aliskiren + Amlodipine In run-in period (4-5 weeks) , patients on thiazide background therapy and approximately 50% of patients on neither CCB nor thiazide background therapy received Amlodipine 5 mg and Aliskiren 150/300 mg daily in a titrated manner as per protocol. In double blind period, patients who successfully completed run-in with Amlodipine plus Aliskiren were randomized equally to the 4 arms of the Amlodipine add-on stratum. Patients randomized to this arm received Aliskiren 300 mg + Amlodipine 5 mg once daily during the double blind period.	Aliskiren + Placebo for Amlodipine In double blind period, all patients who successfully completed run-in with Amlodipine plus aliskiren were randomized equally to the 4 arms of the Amlodipine add-on stratum. In double blind period, randomized patients to this arm received Aliskiren 300 mg + placebo for Amlodipine 5 mg	HCTZ + Placebo for Aliskiren In double blind period, all patients who successfully completed run-in with HCTZ plus Aliskiren were randomized equally to the 4 arms of the HCTZ add-on stratum. In double blind period, randomized patients to this arm received HCTZ 25 mg + placebo for Aliskiren 300 mg once daily	Placebo for Aliskiren + Placebo for HCTZ In double blind period, all patients who successfully completed run-in with HCTZ plus aliskiren were randomized equally to the 4 arms of the HCTZ add-on stratum. In double blind period, randomized patients to this arm received placebo for Aliskiren 300 mg + placebo for HCTZ 25 mg once daily	Amlodipine + Placebo for Aliskiren In double blind period, all patients who successfully completed run-in with Amlodipine plus Aliskiren were randomized equally to the 4 arms of the Amlodipine add-on stratum. In double blind period, randomized patients to this arm received Amlodipine 5 mg + placebo for Aliskiren 300 mg once daily	Placebo for Aliskiren + Placebo for Amlodipine In double blind period, all patients who successfully completed run-in with Amlodipine plus Aliskiren were randomized equally to the 4 arms of the Amlodipine add-on stratum. In double blind period, randomized patients to this arm received placebo for Aliskiren 300 mg + placebo for Amlodipine 5 mg once daily
Run-in Open Label Period (4-5 Weeks) STARTED	1335	0	1001	0	0	0	0	0
Run-in Open Label Period (4-5 Weeks) COMPLETED	980	0	779	0	0	0	0	0
Run-in Open Label Period (4-5 Weeks) NOT COMPLETED	355	0	222	0	0	0	0	0
Double Blind Randomized Period STARTED	244	232	189	195	251	253	196	199
Double Blind Randomized Period COMPLETED	242	229	188	191	247	245	190	196
Double Blind Randomized Period NOT COMPLETED	2	3	1	4	4	8	6	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Aliskiren + Hydrochlorothiazide (HCTZ) In run-in period (4-5 weeks) , patients on CCB background therapy and approximately 50% of patients on neither thiazide nor CCB background therapy: received hydrochlorothiazide 12.5/25 mg and Aliskiren 150/300 mg daily in a titrated manner as per protocol. In double blind period, all patients who successfully completed run-in with HCTZ plus aliskiren were randomized equally to the 4 arms of the HCTZ add-on stratum. Patients randomized to this arm received Aliskiren 300 mg + HCTZ 25 mg once daily.	Aliskiren + Placebo for HCTZ In double blind period, all patients who successfully completed run-in with HCTZ plus Aliskiren were randomized equally to the 4 arms of the HCTZ add-on stratum. In double blind period, randomized patients to this arm received Aliskiren 300 mg + placebo for HCTZ 25 mg once daily	Aliskiren + Amlodipine In run-in period (4-5 weeks) , patients on thiazide background therapy and approximately 50% of patients on neither CCB nor thiazide background therapy received Amlodipine 5 mg and Aliskiren 150/300 mg daily in a titrated manner as per protocol. In double blind period, patients who successfully completed run-in with Amlodipine plus Aliskiren were randomized equally to the 4 arms of the Amlodipine add-on stratum. Patients randomized to this arm received Aliskiren 300 mg + Amlodipine 5 mg once daily during the double blind period.	Aliskiren + Placebo for Amlodipine In double blind period, all patients who successfully completed run-in with Amlodipine plus aliskiren were randomized equally to the 4 arms of the Amlodipine add-on stratum. In double blind period, randomized patients to this arm received Aliskiren 300 mg + placebo for Amlodipine 5 mg	HCTZ + Placebo for Aliskiren In double blind period, all patients who successfully completed run-in with HCTZ plus Aliskiren were randomized equally to the 4 arms of the HCTZ add-on stratum. In double blind period, randomized patients to this arm received HCTZ 25 mg + placebo for Aliskiren 300 mg once daily	Placebo for Aliskiren + Placebo for HCTZ In double blind period, all patients who successfully completed run-in with HCTZ plus aliskiren were randomized equally to the 4 arms of the HCTZ add-on stratum. In double blind period, randomized patients to this arm received placebo for Aliskiren 300 mg + placebo for HCTZ 25 mg once daily	Amlodipine + Placebo for Aliskiren In double blind period, all patients who successfully completed run-in with Amlodipine plus Aliskiren were randomized equally to the 4 arms of the Amlodipine add-on stratum. In double blind period, randomized patients to this arm received Amlodipine 5 mg + placebo for Aliskiren 300 mg once daily	Placebo for Aliskiren + Placebo for Amlodipine In double blind period, all patients who successfully completed run-in with Amlodipine plus Aliskiren were randomized equally to the 4 arms of the Amlodipine add-on stratum. In double blind period, randomized patients to this arm received placebo for Aliskiren 300 mg + placebo for Amlodipine 5 mg once daily
Double Blind Randomized Period Death	1	1	1	2	1	5	2	1
Double Blind Randomized Period Withdrew informed consent/ refused visit	1	1	0	2	2	1	1	1
Double Blind Randomized Period Other reasons	0	1	0	0	1	2	3	1

Baseline Characteristics

A Randomized Controlled Trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly People

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Aliskiren + Hydrochlorothiazide (HCTZ) n=244 Participants In double blind period, all patients who successfully completed run-in with HCTZ plus Aliskiren were randomized equally to the 4 arms of the HCTZ add-on stratum. Patients randomized to this arm received Aliskiren 300 mg + HCTZ 25 mg once daily.	Aliskiren + Placebo for HCTZ n=232 Participants In double blind period, all patients who successfully completed run-in with HCTZ plus Aliskiren were randomized equally to the 4 arms of the HCTZ add-on stratum. In double blind period, randomized patients to this arm received Aliskiren 300 mg + placebo for HCTZ 25 mg once daily	Aliskiren + Amlodipine n=189 Participants In double blind period, all patients who successfully completed run-in with Amlodipine plus Aliskiren were randomized equally to the 4 arms of the Amlodipine add-on stratum. Patients randomized to this arm received Aliskiren 300 mg + Amlodipine 5 mg once daily during the double blind period.	Aliskiren + Placebo for Amlodipine n=195 Participants In double blind period, all patients who successfully completed run-in with Amlodipine plus Aliskiren were randomized equally to the 4 arms of the Amlodipine add-on stratum. In double blind period, randomized patients to this arm received Aliskiren 300 mg + placebo for Amlodipine 5 mg	HCTZ + Placebo for Aliskiren n=251 Participants In double blind period, all patients who successfully completed run-in with HCTZ plus Aliskiren were randomized equally to the 4 arms of the HCTZ add-on stratum. In double blind period, randomized patients to this arm received HCTZ 25 mg + placebo for Aliskiren 300 mg once daily	Placebo for Aliskiren + Placebo for HCTZ n=253 Participants In double blind period, all patients who successfully completed run-in with HCTZ plus Aliskiren were randomized equally to the 4 arms of the HCTZ add-on stratum. In double blind period, randomized patients to this arm received placebo for Aliskiren 300 mg + placebo for HCTZ 25 mg once daily	Amlodipine + Placebo for Aliskiren n=196 Participants In double blind period, all patients who successfully completed run-in with Amlodipine plus Aliskiren were run-in stratum randomized equally to the 4 arms of the Amlodipine add-on stratum. In double blind period, randomized patients to this arm received Amlodipine 5 mg + placebo for Aliskiren 300 mg once daily	Placebo for Aliskiren + Placebo for Amlodipine n=199 Participants In double blind period, all patients who successfully completed run-in with Amlodipine plus Aliskiren were randomized equally to the 4 arms of the Amlodipine add-on stratum. In double blind period, randomized patients to this arm received placebo for Aliskiren 300 mg + placebo for Amlodipine 5 mg once daily	Total n=1759 Participants Total of all reporting groups
Age, Customized >=65 to <75 years	165 participants n=5 Participants	174 participants n=7 Participants	127 participants n=5 Participants	125 participants n=4 Participants	180 participants n=21 Participants	189 participants n=10 Participants	135 participants n=115 Participants	134 participants n=6 Participants	1229 participants n=6 Participants
Age, Customized >=75 years	79 participants n=5 Participants	58 participants n=7 Participants	62 participants n=5 Participants	70 participants n=4 Participants	71 participants n=21 Participants	64 participants n=10 Participants	61 participants n=115 Participants	65 participants n=6 Participants	530 participants n=6 Participants
Sex: Female, Male Female	119 Participants n=5 Participants	109 Participants n=7 Participants	91 Participants n=5 Participants	89 Participants n=4 Participants	122 Participants n=21 Participants	108 Participants n=10 Participants	87 Participants n=115 Participants	88 Participants n=6 Participants	813 Participants n=6 Participants
Sex: Female, Male Male	125 Participants n=5 Participants	123 Participants n=7 Participants	98 Participants n=5 Participants	106 Participants n=4 Participants	129 Participants n=21 Participants	145 Participants n=10 Participants	109 Participants n=115 Participants	111 Participants n=6 Participants	946 Participants n=6 Participants

PRIMARY outcome

Timeframe: End of study (209 days (median))

Population: Full Analysis set. 1759 patients were randomized as against the originally planned 11,000. A total of 25 primary CV composite endpoints had accrued during median follow-up of 209 days versus planned 2000 primary endpoints during planned follow-up of average 5 years. These low numbers significantly limit interpretation of the results.

The composite CV endpoint is based on the following first adjudicated events: CV death, non-fatal MI,non-fatal stroke, significant heart failure

Outcome measures

Outcome measures
Measure	Aliskiren Based Regimen n=860 Participants This regimen includes all the patients who were randomized to the treatment arms that included Aliskiren such as Aliskiren + hydrochlorothiazide (HCTZ), Aliskiren + placebo for HCTZ, Aliskiren + Amlodipine, Aliskiren + placebo for Amlodipine.	Non-Aliskiren Based Regimen n=899 Participants This regimen includes all the patients who were randomized to the treatment arms that did not include Aliskiren such as HCTZ + Placebo for Aliskiren, Placebo for Aliskiren + Placebo for HCTZ, Amlodipine + Placebo for Aliskiren, Placebo for Aliskiren + Placebo for Amlodipine
Number of Participants With Composite Cardiovascular Endpoints in Aliskiren Based Regimen Versus Non-Aliskiren Based Regimen	11 participants	14 participants

PRIMARY outcome

Timeframe: End of study (209 days (median))

The composite CV endpoint is based on the following first adjudicated events: CV death, non-fatal MI,non-fatal stroke, significant heart failure

Outcome measures

Outcome measures
Measure	Aliskiren Based Regimen n=433 Participants This regimen includes all the patients who were randomized to the treatment arms that included Aliskiren such as Aliskiren + hydrochlorothiazide (HCTZ), Aliskiren + placebo for HCTZ, Aliskiren + Amlodipine, Aliskiren + placebo for Amlodipine.	Non-Aliskiren Based Regimen n=452 Participants This regimen includes all the patients who were randomized to the treatment arms that did not include Aliskiren such as HCTZ + Placebo for Aliskiren, Placebo for Aliskiren + Placebo for HCTZ, Amlodipine + Placebo for Aliskiren, Placebo for Aliskiren + Placebo for Amlodipine
Number of Participants With Composite Cardiovascular Endpoints in Aliskiren+Amlodipine/HCTZ Group Versus All Placebo Group	2 participants	8 participants

SECONDARY outcome

Timeframe: Baseline, End of study (209 days [median])

Population: Full Analysis Set: Due to the sparse post-baseline data following early termination of the study, this analysis was not performed as planned in protocol.Hence, no meaningful conclusion could be drawn. Patients who completed both baseline and post-baseline SAGE questionnaires (Part II) were included in this analysis.

Decline in ability to perform everyday activities independently was measured primarily by using the Standard Assessment of Global Activities in the Elderly (SAGE) scale. The SAGE comprised of 15 questions, each describing an activity. Patient had to indicate how much difficulty he/she had encountered in performing the activity in last month. Each question's score ranges from 0 (No difficulty) to 3 (difficulty levels were mild (score = 1), moderate (score =2) and severe (score=3)). Part I of SAGE included 4 dimensions: * Community Cognition (maximum of scores of questions 1 to 6); * Instrumental Activities of daily Living (IADL) (maximum of scores of questions 7 to 10); * Mobility (maximum of scores of questions 11 and 12);. * Basic Activities of daily Living (ADL) (maximum of scores of questions 13 to 15) Each dimension's total score ranged from 0 to 3. 0=best, 3=worst A negative change in value from baseline means improvement in the ability to perform everyday activities.

Outcome measures

Outcome measures
Measure	Aliskiren Based Regimen n=592 Participants This regimen includes all the patients who were randomized to the treatment arms that included Aliskiren such as Aliskiren + hydrochlorothiazide (HCTZ), Aliskiren + placebo for HCTZ, Aliskiren + Amlodipine, Aliskiren + placebo for Amlodipine.	Non-Aliskiren Based Regimen n=618 Participants This regimen includes all the patients who were randomized to the treatment arms that did not include Aliskiren such as HCTZ + Placebo for Aliskiren, Placebo for Aliskiren + Placebo for HCTZ, Amlodipine + Placebo for Aliskiren, Placebo for Aliskiren + Placebo for Amlodipine
Change From Baseline to End of Study in Standard Assessment of Global Activities in the Elderly (SAGE) Dimensions (Part I) Instrumental Activities of daily Living (IADL)	-0.06 units on a scale Standard Deviation 0.562	-0.04 units on a scale Standard Deviation 0.505
Change From Baseline to End of Study in Standard Assessment of Global Activities in the Elderly (SAGE) Dimensions (Part I) ADL	-0.09 units on a scale Standard Deviation 0.525	-0.08 units on a scale Standard Deviation 0.520
Change From Baseline to End of Study in Standard Assessment of Global Activities in the Elderly (SAGE) Dimensions (Part I) Community Cognition	-0.04 units on a scale Standard Deviation 0.768	-0.05 units on a scale Standard Deviation 0.741
Change From Baseline to End of Study in Standard Assessment of Global Activities in the Elderly (SAGE) Dimensions (Part I) Mobility	0.01 units on a scale Standard Deviation 0.791	0.00 units on a scale Standard Deviation 0.779

SECONDARY outcome

Timeframe: End of study (209 days [median])

Population: Full Analysis Set. Number of patients with all SAGE questions non-missing for the specific visit are included in this population. Due to the sparse post-baseline data following early termination of the study, this analysis was not performed as planned in protocol.Hence, no meaningful conclusion could be drawn.

Outcome measures

Outcome measures
Measure	Aliskiren Based Regimen n=608 Participants This regimen includes all the patients who were randomized to the treatment arms that included Aliskiren such as Aliskiren + hydrochlorothiazide (HCTZ), Aliskiren + placebo for HCTZ, Aliskiren + Amlodipine, Aliskiren + placebo for Amlodipine.	Non-Aliskiren Based Regimen n=641 Participants This regimen includes all the patients who were randomized to the treatment arms that did not include Aliskiren such as HCTZ + Placebo for Aliskiren, Placebo for Aliskiren + Placebo for HCTZ, Amlodipine + Placebo for Aliskiren, Placebo for Aliskiren + Placebo for Amlodipine
Percentage of Participants With Standard Assessment of Global Activities in the Elderly (SAGE) Dimensions (Part II) Normal	44.2 percentage of participants	46.5 percentage of participants
Percentage of Participants With Standard Assessment of Global Activities in the Elderly (SAGE) Dimensions (Part II) Mobility Only	66.8 percentage of participants	68.6 percentage of participants

SECONDARY outcome

Timeframe: End of study (209 days (median))

Population: Full Analysis set. 1759 patients were randomized as against the originally planned 11,000. The duration of study follow-up was 209 days (median) as against the planned follow-up of average 5 years. These low numbers significantly limit interpretation of the results.

The renal dysfunction (composite endpoint) was defined as the first occurrence of either of the following: * End-stage renal disease \[ESRD\] requiring dialysis or transplantation * Doubling of serum creatinine and reaching an eGFR \< 45 ml/min/1.73 m\^2.

Outcome measures

Outcome measures
Measure	Aliskiren Based Regimen n=860 Participants This regimen includes all the patients who were randomized to the treatment arms that included Aliskiren such as Aliskiren + hydrochlorothiazide (HCTZ), Aliskiren + placebo for HCTZ, Aliskiren + Amlodipine, Aliskiren + placebo for Amlodipine.	Non-Aliskiren Based Regimen n=899 Participants This regimen includes all the patients who were randomized to the treatment arms that did not include Aliskiren such as HCTZ + Placebo for Aliskiren, Placebo for Aliskiren + Placebo for HCTZ, Amlodipine + Placebo for Aliskiren, Placebo for Aliskiren + Placebo for Amlodipine
Number of Participants With Renal Dysfunction in Aliskiren Based Regimen Versus Non-Aliskiren Based Regimen ESRD requiring dialysis or transplantation	0 participants	0 participants
Number of Participants With Renal Dysfunction in Aliskiren Based Regimen Versus Non-Aliskiren Based Regimen Doubling of creatinine & eGFR<45 ml/min/1.73 m^2	7 participants	1 participants

SECONDARY outcome

Timeframe: End of study (209 days (median))

The total mortality endpoint was defined as time to death from any cause. Total mortality analysis used the date of last follow-up including the washout period as the censoring date.

Outcome measures

Outcome measures
Measure	Aliskiren Based Regimen n=860 Participants This regimen includes all the patients who were randomized to the treatment arms that included Aliskiren such as Aliskiren + hydrochlorothiazide (HCTZ), Aliskiren + placebo for HCTZ, Aliskiren + Amlodipine, Aliskiren + placebo for Amlodipine.	Non-Aliskiren Based Regimen n=899 Participants This regimen includes all the patients who were randomized to the treatment arms that did not include Aliskiren such as HCTZ + Placebo for Aliskiren, Placebo for Aliskiren + Placebo for HCTZ, Amlodipine + Placebo for Aliskiren, Placebo for Aliskiren + Placebo for Amlodipine
Number of Participants With Total Mortality in Aliskiren Based Regimen Versus Non-aliskiren Based Regimen	5 Participants	9 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (BL), 6 week, 6 month and 12 month

Population: Full analysis Set : All randomized patients, regardless of receiving study medication. n=number of patients with non-missing assessments at baseline and each post-baseline visit.

Mean sitting systolic blood pressure (msSBP) is the average of 2 sitting SBP measurements (2 minutes apart). Since each patient had their final follow-up visit at a different time in the trial, these measurements were classified as falling into the 6 week, 6 month, or 12 month measurement period. All available blood pressures were sorted within these periods and the last value within each time range used for analysis. At each timepoint, a patient must have both baseline and postbaseline values to be included in the analysis.

Outcome measures

Outcome measures
Measure	Aliskiren Based Regimen n=860 Participants This regimen includes all the patients who were randomized to the treatment arms that included Aliskiren such as Aliskiren + hydrochlorothiazide (HCTZ), Aliskiren + placebo for HCTZ, Aliskiren + Amlodipine, Aliskiren + placebo for Amlodipine.	Non-Aliskiren Based Regimen n=899 Participants This regimen includes all the patients who were randomized to the treatment arms that did not include Aliskiren such as HCTZ + Placebo for Aliskiren, Placebo for Aliskiren + Placebo for HCTZ, Amlodipine + Placebo for Aliskiren, Placebo for Aliskiren + Placebo for Amlodipine
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) change from Baseline to 6 week (n=821,867)	-11.9 mmHg Standard Error 0.50	-8.02 mmHg Standard Error 0.48
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) change from baseline to 6 month (n=730,775)	-10.1 mmHg Standard Error 0.52	-6.8 mmHg Standard Error 0.50
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) change from baseline to 12 month (n=397,399)	-7.7 mmHg Standard Error 0.68	-5.8 mmHg Standard Error 0.68

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (BL), 6 week, 6 month and 12 month

Population: Full analysis Set : All randomized patients, regardless of receiving study medication. n=number of patients with non-missing assessments at baseline and each post-baseline visit.

Mean sitting diastolic blood pressure (msDBP) is the average of 2 sitting DBP measurements (2 minutes apart). Since each patient had their final follow-up visit at a different time in the trial, these measurements were classified as falling into the 6 week, 6 month, or 12 month measurement period. All available blood pressures were sorted within these periods and the last value within each time range used for analysis. At each timepoint, a patient must have both baseline and postbaseline values to be included in the analysis.

Outcome measures

Outcome measures
Measure	Aliskiren Based Regimen n=860 Participants This regimen includes all the patients who were randomized to the treatment arms that included Aliskiren such as Aliskiren + hydrochlorothiazide (HCTZ), Aliskiren + placebo for HCTZ, Aliskiren + Amlodipine, Aliskiren + placebo for Amlodipine.	Non-Aliskiren Based Regimen n=899 Participants This regimen includes all the patients who were randomized to the treatment arms that did not include Aliskiren such as HCTZ + Placebo for Aliskiren, Placebo for Aliskiren + Placebo for HCTZ, Amlodipine + Placebo for Aliskiren, Placebo for Aliskiren + Placebo for Amlodipine
Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) change from baseline to 12 month (n=397,399)	-4.3 mmHg Standard Error 0.43	-3.9 mmHg Standard Error 0.43
Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) change from Baseline to 6 week (n=821,867)	-5.6 mmHg Standard Error 0.31	-3.6 mmHg Standard Error 0.30
Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) change from baseline to 6 month (n=730,775)	-4.9 mmHg Standard Error 0.33	-3.5 mmHg Standard Error 0.32

Adverse Events

Run-in Period: Aliskiren + Hydrochlorothiazide (HCTZ)

Serious events: 10 serious events

Other events: 7 other events

Deaths: 0 deaths

Run-in Period: Aliskiren + Amlodipine

Serious events: 10 serious events

Other events: 19 other events

Deaths: 0 deaths

Double Blind Period: Aliskiren + Hydrochlorothiazide (HCTZ)

Serious events: 8 serious events

Other events: 6 other events

Deaths: 0 deaths

Double Blind Period: Aliskiren + Placebo for HCTZ

Serious events: 5 serious events

Other events: 5 other events

Deaths: 0 deaths

Double Blind Period: Aliskiren + Amlodipine

Serious events: 7 serious events

Other events: 9 other events

Deaths: 0 deaths

Double Blind Period: Aliskiren + Placebo for Amlodipine

Serious events: 8 serious events

Other events: 8 other events

Deaths: 0 deaths

Double Blind Period: HCTZ + Placebo for Aliskiren

Serious events: 4 serious events

Other events: 6 other events

Deaths: 0 deaths

Double Blind Period: Placebo for Aliskiren + Placebo for HCTZ

Serious events: 6 serious events

Other events: 5 other events

Deaths: 0 deaths

Double Blind Period: Amlodipine + Placebo for Aliskiren

Serious events: 3 serious events

Other events: 14 other events

Deaths: 0 deaths

Double Blind Period: Placebo for Aliskiren + Placebo for Amlod

Serious events: 7 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Run-in Period: Aliskiren + Hydrochlorothiazide (HCTZ) n=1335 participants at risk In run-in period (4-5 weeks) , patients on CCB background therapy and approximately 50% of patients on neither thiazide nor CCB background therapy: received Hydrochlorothiazide 12.5/25 mg and Aliskiren 150/300 mg daily in a titrated manner as per protocol. Patients randomized to this arm received Aliskiren 300 mg + HCTZ 25 mg once daily.	Run-in Period: Aliskiren + Amlodipine n=1001 participants at risk In run-in period (4-5 weeks) , patients on thiazide background therapy and approximately 50% of patients on neither CCB nor thiazide background therapy received Amlodipine 5 mg and Aliskiren 150/300 mg daily in a titrated manner as per protocol. Patients randomized to this arm received Aliskiren 300 mg + Amlodipine 5 mg once daily during the double blind period.	Double Blind Period: Aliskiren + Hydrochlorothiazide (HCTZ) n=244 participants at risk In double blind period, all patients who successfully completed run-in with HCTZ plus Aliskiren were randomized equally to the 4 arms of the HCTZ add-on stratum. Patients randomized to this arm received Aliskiren 300 mg + HCTZ 25 mg once daily.	Double Blind Period: Aliskiren + Placebo for HCTZ n=232 participants at risk In double blind period, all patients who successfully completed run-in with HCTZ plus Aliskiren were randomized equally to the 4 arms of the HCTZ add-on stratum. In double blind period, randomized patients to this arm received Aliskiren 300 mg + placebo for HCTZ 25 mg once daily	Double Blind Period: Aliskiren + Amlodipine n=189 participants at risk In double blind period, patients who successfully completed run-in with Amlodipine plus Aliskiren were randomized equally to the 4 arms of the Amlodipine add-on stratum. Patients randomized to this arm received Aliskiren 300 mg + Amlodipine 5 mg once daily during the double blind period.	Double Blind Period: Aliskiren + Placebo for Amlodipine n=195 participants at risk In double blind period, all patients who successfully completed run-in with Amlodipine plus Aliskiren were randomized equally to the 4 arms of the Amlodipine add-on stratum. In double blind period, randomized patients to this arm received Aliskiren 300 mg + placebo for Amlodipine 5 mg	Double Blind Period: HCTZ + Placebo for Aliskiren n=251 participants at risk In double blind period, all patients who successfully completed run-in with HCTZ plus Aliskiren were randomized equally to the 4 arms of the HCTZ add-on stratum. In double blind period, randomized patients to this arm received HCTZ 25 mg + placebo for Aliskiren 300 mg once daily	Double Blind Period: Placebo for Aliskiren + Placebo for HCTZ n=253 participants at risk In double blind period, all patients who successfully completed run-in with HCTZ plus Aliskiren were randomized equally to the 4 arms of the HCTZ add-on stratum. In double blind period, randomized patients to this arm received placebo for Aliskiren 300 mg + placebo for HCTZ 25 mg once daily	Double Blind Period: Amlodipine + Placebo for Aliskiren n=196 participants at risk In double blind period, all patients who successfully completed run-in with Amlodipine plus Aliskiren were randomized equally to the 4 arms of the Amlodipine add-on stratum. In double blind period, randomized patients to this arm received Amlodipine 5 mg + placebo for Aliskiren 300 mg once daily	Double Blind Period: Placebo for Aliskiren + Placebo for Amlod n=199 participants at risk In double blind period, all patients who successfully completed run-in with Amlodipine plus Aliskiren were randomized equally to the 4 arms of the Amlodipine add-on stratum. In double blind period, randomized patients to this arm received placebo for Aliskiren 300 mg + placebo for Amlodipine 5 mg once daily
Blood and lymphatic system disorders Anaemia	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.10% 1/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.41% 1/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Cardiac disorders Angina pectoris	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.41% 1/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Cardiac disorders Atrial fibrillation	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.40% 1/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.51% 1/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Cardiac disorders Cardiac arrest	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.40% 1/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Cardiac disorders Ventricular fibrillation	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.40% 1/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Gastrointestinal disorders Abdominal hernia	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.40% 1/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Gastrointestinal disorders Diarrhoea	0.07% 1/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.40% 1/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.50% 1/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.10% 1/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Gastrointestinal disorders Haematochezia	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.50% 1/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Gastrointestinal disorders Intestinal perforation	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.50% 1/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.51% 1/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
General disorders Chest pain	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.10% 1/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
General disorders Drug interaction	0.07% 1/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
General disorders Drug intolerance	0.07% 1/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Hepatobiliary disorders Cholecystitis	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.51% 1/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.40% 1/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Infections and infestations Bronchitis	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.10% 1/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Infections and infestations Cellulitis	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.51% 1/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.40% 1/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Infections and infestations Gastroenteritis	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.43% 1/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Infections and infestations Herpes zoster	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.40% 1/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Infections and infestations Pneumonia	0.07% 1/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.40% 1/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Infections and infestations Urinary tract infection	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.51% 1/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.40% 1/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Infections and infestations Viral infection	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.41% 1/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.43% 1/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Injury, poisoning and procedural complications Subdural haematoma	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.50% 1/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Investigations Blood creatinine increased	0.07% 1/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Investigations Blood urea increased	0.07% 1/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.40% 1/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Metabolism and nutrition disorders Electrolyte imbalance	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.53% 1/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Metabolism and nutrition disorders Hyperkalaemia	0.15% 2/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.10% 1/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.41% 1/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	1.6% 3/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.51% 1/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.51% 1/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Metabolism and nutrition disorders Hypokalaemia	0.15% 2/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Metabolism and nutrition disorders Hyponatraemia	0.07% 1/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.41% 1/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.10% 1/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.53% 1/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.50% 1/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer metastatic	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.10% 1/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Small intestine carcinoma	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.43% 1/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Nervous system disorders Cerebral hypoperfusion	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.50% 1/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Nervous system disorders Cerebrovascular accident	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.40% 1/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Nervous system disorders Coma	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.40% 1/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Nervous system disorders Hemiparesis	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.53% 1/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Nervous system disorders Loss of consciousness	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.10% 1/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Nervous system disorders Paraesthesia	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.53% 1/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Nervous system disorders Syncope	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.10% 1/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	1.2% 3/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.53% 1/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Psychiatric disorders Psychotic disorder	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.53% 1/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Renal and urinary disorders Azotaemia	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.51% 1/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Renal and urinary disorders Renal disorder	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.51% 1/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Renal and urinary disorders Renal failure	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.82% 2/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.43% 1/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Renal and urinary disorders Renal failure acute	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.43% 1/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Renal and urinary disorders Renal impairment	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.43% 1/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.51% 1/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Skin and subcutaneous tissue disorders Angioedema	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.20% 2/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.51% 1/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.50% 1/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Vascular disorders Arterial occlusive disease	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.51% 1/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Vascular disorders Hypertensive crisis	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.51% 1/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Vascular disorders Hypotension	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.20% 2/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.

Other adverse events

Other adverse events
Measure	Run-in Period: Aliskiren + Hydrochlorothiazide (HCTZ) n=1335 participants at risk In run-in period (4-5 weeks) , patients on CCB background therapy and approximately 50% of patients on neither thiazide nor CCB background therapy: received Hydrochlorothiazide 12.5/25 mg and Aliskiren 150/300 mg daily in a titrated manner as per protocol. Patients randomized to this arm received Aliskiren 300 mg + HCTZ 25 mg once daily.	Run-in Period: Aliskiren + Amlodipine n=1001 participants at risk In run-in period (4-5 weeks) , patients on thiazide background therapy and approximately 50% of patients on neither CCB nor thiazide background therapy received Amlodipine 5 mg and Aliskiren 150/300 mg daily in a titrated manner as per protocol. Patients randomized to this arm received Aliskiren 300 mg + Amlodipine 5 mg once daily during the double blind period.	Double Blind Period: Aliskiren + Hydrochlorothiazide (HCTZ) n=244 participants at risk In double blind period, all patients who successfully completed run-in with HCTZ plus Aliskiren were randomized equally to the 4 arms of the HCTZ add-on stratum. Patients randomized to this arm received Aliskiren 300 mg + HCTZ 25 mg once daily.	Double Blind Period: Aliskiren + Placebo for HCTZ n=232 participants at risk In double blind period, all patients who successfully completed run-in with HCTZ plus Aliskiren were randomized equally to the 4 arms of the HCTZ add-on stratum. In double blind period, randomized patients to this arm received Aliskiren 300 mg + placebo for HCTZ 25 mg once daily	Double Blind Period: Aliskiren + Amlodipine n=189 participants at risk In double blind period, patients who successfully completed run-in with Amlodipine plus Aliskiren were randomized equally to the 4 arms of the Amlodipine add-on stratum. Patients randomized to this arm received Aliskiren 300 mg + Amlodipine 5 mg once daily during the double blind period.	Double Blind Period: Aliskiren + Placebo for Amlodipine n=195 participants at risk In double blind period, all patients who successfully completed run-in with Amlodipine plus Aliskiren were randomized equally to the 4 arms of the Amlodipine add-on stratum. In double blind period, randomized patients to this arm received Aliskiren 300 mg + placebo for Amlodipine 5 mg	Double Blind Period: HCTZ + Placebo for Aliskiren n=251 participants at risk In double blind period, all patients who successfully completed run-in with HCTZ plus Aliskiren were randomized equally to the 4 arms of the HCTZ add-on stratum. In double blind period, randomized patients to this arm received HCTZ 25 mg + placebo for Aliskiren 300 mg once daily	Double Blind Period: Placebo for Aliskiren + Placebo for HCTZ n=253 participants at risk In double blind period, all patients who successfully completed run-in with HCTZ plus Aliskiren were randomized equally to the 4 arms of the HCTZ add-on stratum. In double blind period, randomized patients to this arm received placebo for Aliskiren 300 mg + placebo for HCTZ 25 mg once daily	Double Blind Period: Amlodipine + Placebo for Aliskiren n=196 participants at risk In double blind period, all patients who successfully completed run-in with Amlodipine plus Aliskiren were randomized equally to the 4 arms of the Amlodipine add-on stratum. In double blind period, randomized patients to this arm received Amlodipine 5 mg + placebo for Aliskiren 300 mg once daily	Double Blind Period: Placebo for Aliskiren + Placebo for Amlod n=199 participants at risk In double blind period, all patients who successfully completed run-in with Amlodipine plus Aliskiren were randomized equally to the 4 arms of the Amlodipine add-on stratum. In double blind period, randomized patients to this arm received placebo for Aliskiren 300 mg + placebo for Amlodipine 5 mg once daily
Gastrointestinal disorders Gastritis	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	1.0% 2/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.51% 1/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.50% 1/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
General disorders Oedema peripheral	0.00% 0/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.70% 7/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.43% 1/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	2.1% 4/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.79% 2/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	3.6% 7/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.50% 1/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Metabolism and nutrition disorders Hyperkalaemia	0.07% 1/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.41% 1/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.43% 1/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	1.0% 2/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.40% 1/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.40% 1/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.51% 1/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Nervous system disorders Dizziness	0.22% 3/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.70% 7/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.41% 1/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	1.0% 2/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.40% 1/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.40% 1/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.00% 0/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.
Vascular disorders Hypotension	0.22% 3/1335 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.50% 5/1001 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	1.6% 4/244 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	1.3% 3/232 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	3.2% 6/189 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	1.0% 2/195 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	1.6% 4/251 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.40% 1/253 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	2.6% 5/196 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.	0.50% 1/199 Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: [email protected]

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 or disclosure of trial results in their entirety.
Publication restrictions are in place

Restriction type: OTHER