Trial Outcomes & Findings for Effects of Aliskiren and Amlodipine on the Renin-Angiotensin System (RAS) and Lipid/Carbohydrate Metabolism in Obese Patients With Hypertension (NCT NCT00498433)

NCT ID: NCT00498433

Last Updated: 2014-09-10

Results Overview

Interstitial fluid was obtained from subcutaneous adipose and skeletal muscle tissues by microdialysis using the zero-flow method. Interstitial fluid was collected for measurements of drug concentrations on the last day of the aliskiren treatment periods (Day 42).

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 46 participants
• Primary outcome timeframe: Day 42
• Results posted on: 2014-09-10

Participant Flow

Total 46 patients entered into the study; 10 patients in part 1 received study drug. 36 patients enrolled into part 2 and and 16 patients received study drug.

Participant milestones

Measure	Placebo Part 1, Period 1: After a 1-2 weeks initial washout period, all eligible patients underwent a two week placebo run-in phase. Part 2, Period 1: After confirming study eligibility based on inclusion and exclusion criteria, patients underwent a two week single-blind placebo run-in phase.	Aliskiren Part 1 , Period 2: All eligible patients received 4 week treatment of 300 mg aliskiren o.d.. Part 2, Double Blind Period: Eligible randomized patients received aliskiren 300 mg tablet o.d. and amlodipine placebo capsule o.d. for 12 weeks	Amlodipine Part 1, Period 3: All patients received 5 mg amlodipine o.d.. The length of the amlodipine period varied from 4 to 7 weeks. Part 2, Double Blind Period: Eligible randomized patients received amlodipine 5 mg o.d. and aliskiren placebo o.d. for 12 weeks
Part 1, Period 1:Placebo Run-in(2 Weeks) STARTED	10	0	0
Part 1, Period 1:Placebo Run-in(2 Weeks) COMPLETED	10	0	0
Part 1, Period 1:Placebo Run-in(2 Weeks) NOT COMPLETED	0	0	0
Part 1, Period 2: Aliskiren (4 Weeks) STARTED	0	10	0
Part 1, Period 2: Aliskiren (4 Weeks) COMPLETED	0	10	0
Part 1, Period 2: Aliskiren (4 Weeks) NOT COMPLETED	0	0	0
Part 1, Period 3: Amlodipine (4-8 Weeks) STARTED	0	0	10
Part 1, Period 3: Amlodipine (4-8 Weeks) COMPLETED	0	0	10
Part 1, Period 3: Amlodipine (4-8 Weeks) NOT COMPLETED	0	0	0
Part 2: Placebo Run-in (2 Weeks) STARTED	36	0	0
Part 2: Placebo Run-in (2 Weeks) COMPLETED	16	0	0
Part 2: Placebo Run-in (2 Weeks) NOT COMPLETED	20	0	0
Part 2: Double Blind (12 Weeks) STARTED	0	8	8
Part 2: Double Blind (12 Weeks) COMPLETED	0	8	8
Part 2: Double Blind (12 Weeks) NOT COMPLETED	0	0	0

Reasons for withdrawal

Measure	Placebo Part 1, Period 1: After a 1-2 weeks initial washout period, all eligible patients underwent a two week placebo run-in phase. Part 2, Period 1: After confirming study eligibility based on inclusion and exclusion criteria, patients underwent a two week single-blind placebo run-in phase.	Aliskiren Part 1 , Period 2: All eligible patients received 4 week treatment of 300 mg aliskiren o.d.. Part 2, Double Blind Period: Eligible randomized patients received aliskiren 300 mg tablet o.d. and amlodipine placebo capsule o.d. for 12 weeks	Amlodipine Part 1, Period 3: All patients received 5 mg amlodipine o.d.. The length of the amlodipine period varied from 4 to 7 weeks. Part 2, Double Blind Period: Eligible randomized patients received amlodipine 5 mg o.d. and aliskiren placebo o.d. for 12 weeks
Part 2: Placebo Run-in (2 Weeks) Adverse Event	2	0	0
Part 2: Placebo Run-in (2 Weeks) Abnormal laboratory value	2	0	0
Part 2: Placebo Run-in (2 Weeks) Abnormal test procedure	15	0	0
Part 2: Placebo Run-in (2 Weeks) Administrative problems	1	0	0

Baseline Characteristics

Effects of Aliskiren and Amlodipine on the Renin-Angiotensin System (RAS) and Lipid/Carbohydrate Metabolism in Obese Patients With Hypertension

Baseline characteristics by cohort

Measure	Part 1: Placebo/Aliskiren/Amlodipine n=10 Participants Part 1, Period 1: After a 1-2 weeks initial washout period, all eligible patients underwent a two week placebo run-in phase. Part 1 , Period 2: All eligible patients received 4 week treatment of 300 mg aliskiren o.d.. Part 1, Period 3: All patients received 5 mg amlodipine o.d.. The length of the amlodipine period varied from 4 to 7 weeks.	Part 2, Double Blind Period: Aliskiren n=8 Participants Eligible randomized patients received aliskiren 300 mg tablet o.d. and amlodipine placebo capsule o.d. for 12 weeks	Part 2, Double Blind: Amlodipine n=8 Participants Eligible randomized patients received amlodipine 5 mg o.d. and aliskiren placebo o.d. for 12 weeks	Total n=26 Participants Total of all reporting groups
Age, Continuous Part 1, Open Label	46 years STANDARD_DEVIATION 7.5 • n=5 Participants	NA years STANDARD_DEVIATION NA • n=7 Participants	NA years STANDARD_DEVIATION NA • n=5 Participants	46 years STANDARD_DEVIATION 7.5 • n=4 Participants
Age, Continuous Part 2, Double blind	NA years STANDARD_DEVIATION NA • n=5 Participants	46.0 years STANDARD_DEVIATION 10.92 • n=7 Participants	49.4 years STANDARD_DEVIATION 10.53 • n=5 Participants	47.7 years STANDARD_DEVIATION 10.17 • n=4 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	20 Participants n=4 Participants

PRIMARY outcome

Timeframe: Day 42

Population: All patients who received at least one dose of study drug and had at least one post-baseline assessment of pharmacokinetics (PK)/ pharmacodynamics (PD) data were included in the data analysis.

Interstitial fluid was obtained from subcutaneous adipose and skeletal muscle tissues by microdialysis using the zero-flow method. Interstitial fluid was collected for measurements of drug concentrations on the last day of the aliskiren treatment periods (Day 42).

Outcome measures

Measure	Part 1: Placebo/Aliskiren/Amlodipine n=10 Participants Part 1, Period 1: After a 1-2 weeks initial washout period, all eligible patients underwent a two week placebo run-in phase. Part 1 , Period 2: All eligible patients received 4 week treatment of 300 mg aliskiren o.d.. Part 1, Period 3: All patients received 5 mg amlodipine o.d.. The length of the amlodipine period varied from 4 to 7 weeks.	Amlodipine Part 2, Double Blind Period: Eligible randomized patients received amlodipine 5 mg o.d. and aliskiren placebo o.d. for 12 weeks	Amlodipine Part 2, Double Blind: Eligible randomized patients of this arm received amlodipine 5 mg o.d. and aliskiren placebo o.d. for 12 weeks
Part 1: Aliskiren Concentrations From Interstitial Fluid (Microdialysis)at the End of Aliskiren Treatment Period Adipose tissue	2.38 ng/mL Standard Deviation 2.11	—	—
Part 1: Aliskiren Concentrations From Interstitial Fluid (Microdialysis)at the End of Aliskiren Treatment Period Skeletal muscle	7.05 ng/mL Standard Deviation 4.24	—	—

PRIMARY outcome

Timeframe: Day 98

Population: Zero flow concentrations from microdialysates could not be derived by linear regression because of missing data due to inadequate sample volumes.

Interstitial fluid was obtained from subcutaneous adipose and skeletal muscle tissues by microdialysis using the zero-flow method. Interstitial fluid was collected for measurements of drug concentration on the last day of the amlodipine treatment periods (Day 98).

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Day 42

Population: Due to technical limitations, zero flow concentrations could not be derived for Ang II.

Interstitial fluid was obtained from subcutaneous adipose and skeletal muscle tissues by microdialysis using the zero-flow method to determine Ang II concentration.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Day 98

Population: Due to technical limitations, zero flow concentrations could not be derived for Ang II.

Interstitial fluid was obtained from subcutaneous adipose and skeletal muscle tissues by microdialysis using the zero-flow method to determine Ang II concentration.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Day 42

Population: All patients who received at least one dose of study drug and had at least one post-baseline assessment of pharmacokinetics data were included in the data analysis.

Biopsies were taken from abdominal adipose and skeletal muscle tissue to determine aliskiren concentration. Tissue biopsy samples for drug concentrations analyses were taken on the last day of the aliskiren treatment periods (Day 42).

Outcome measures

Measure	Part 1: Placebo/Aliskiren/Amlodipine n=9 Participants Part 1, Period 1: After a 1-2 weeks initial washout period, all eligible patients underwent a two week placebo run-in phase. Part 1 , Period 2: All eligible patients received 4 week treatment of 300 mg aliskiren o.d.. Part 1, Period 3: All patients received 5 mg amlodipine o.d.. The length of the amlodipine period varied from 4 to 7 weeks.	Amlodipine Part 2, Double Blind Period: Eligible randomized patients received amlodipine 5 mg o.d. and aliskiren placebo o.d. for 12 weeks	Amlodipine Part 2, Double Blind: Eligible randomized patients of this arm received amlodipine 5 mg o.d. and aliskiren placebo o.d. for 12 weeks
Part 1: Aliskiren Concentrations From Tissue at the End of Aliskiren Treatment Period Adipose tissue (n=6)	29.05 ng/g Standard Deviation 16.71	—	—
Part 1: Aliskiren Concentrations From Tissue at the End of Aliskiren Treatment Period Skeletal muscle (n=9)	107.32 ng/g Standard Deviation 68.64	—	—

PRIMARY outcome

Timeframe: Day 42

Population: More than 50% of the biopsy samples over all time points were either below lower limit of quantification (LLOQ) or not received.

Biopsies were taken from abdominal adipose and skeletal muscle tissue to determine Ang II concentration.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Day 42

Population: Renin activity and concentration from adipose tissue and skeletal muscles were all below lower limitation of quantification (LLOQ) at all time points.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Day 42

Population: All patients who received at least one dose of study drug and had at least one post-baseline assessment of pharmacokinetics data were included in the data analysis.

Plasma samples were obtained for measurement of aliskiren or amlodipine concentrations. All blood samples were taken by an indwelling cannula inserted in a forearm vein or direct venipuncture. The plasma samples for drug concentrations analyses were taken on the last day of the aliskiren treatment periods (Day 42).

Outcome measures

Measure	Part 1: Placebo/Aliskiren/Amlodipine n=10 Participants Part 1, Period 1: After a 1-2 weeks initial washout period, all eligible patients underwent a two week placebo run-in phase. Part 1 , Period 2: All eligible patients received 4 week treatment of 300 mg aliskiren o.d.. Part 1, Period 3: All patients received 5 mg amlodipine o.d.. The length of the amlodipine period varied from 4 to 7 weeks.	Amlodipine Part 2, Double Blind Period: Eligible randomized patients received amlodipine 5 mg o.d. and aliskiren placebo o.d. for 12 weeks	Amlodipine Part 2, Double Blind: Eligible randomized patients of this arm received amlodipine 5 mg o.d. and aliskiren placebo o.d. for 12 weeks
Part 1: Aliskiren Concentrations From Plasma at the End of Aliskiren Treatment Period	8.38 ng/mL Standard Deviation 4.41	—	—

PRIMARY outcome

Timeframe: Day 98

Population: All patients who received at least one dose of study drug and had at least one post-baseline assessment of pharmacokinetics data were included in the data analysis.

Plasma samples were obtained for measurement of aliskiren or amlodipine concentrations. All blood samples were taken by an indwelling cannula inserted in a forearm vein or direct venipuncture. The plasma samples for drug concentrations analyses were taken on the last day of the amlodipine treatment periods (Day 98).

Outcome measures

Measure	Part 1: Placebo/Aliskiren/Amlodipine n=10 Participants Part 1, Period 1: After a 1-2 weeks initial washout period, all eligible patients underwent a two week placebo run-in phase. Part 1 , Period 2: All eligible patients received 4 week treatment of 300 mg aliskiren o.d.. Part 1, Period 3: All patients received 5 mg amlodipine o.d.. The length of the amlodipine period varied from 4 to 7 weeks.	Amlodipine Part 2, Double Blind Period: Eligible randomized patients received amlodipine 5 mg o.d. and aliskiren placebo o.d. for 12 weeks	Amlodipine Part 2, Double Blind: Eligible randomized patients of this arm received amlodipine 5 mg o.d. and aliskiren placebo o.d. for 12 weeks
Part 1: Amlodipine Concentrations From Plasma at the End of Amlodipine Treatment Period	7.78 ng/mL Standard Deviation 3.61	—	—

PRIMARY outcome

Timeframe: Day 42

Population: All patients who received at least one dose of study drug and had at least one post-baseline assessment of pharmacodynamic data were included in the data analysis.

Interstitial fluid was obtained from subcutaneous adipose and skeletal muscle tissues by microdialysis using the zero-flow method to determine Ang II concentration.

Outcome measures

Measure	Part 1: Placebo/Aliskiren/Amlodipine n=10 Participants Part 1, Period 1: After a 1-2 weeks initial washout period, all eligible patients underwent a two week placebo run-in phase. Part 1 , Period 2: All eligible patients received 4 week treatment of 300 mg aliskiren o.d.. Part 1, Period 3: All patients received 5 mg amlodipine o.d.. The length of the amlodipine period varied from 4 to 7 weeks.	Amlodipine Part 2, Double Blind Period: Eligible randomized patients received amlodipine 5 mg o.d. and aliskiren placebo o.d. for 12 weeks	Amlodipine Part 2, Double Blind: Eligible randomized patients of this arm received amlodipine 5 mg o.d. and aliskiren placebo o.d. for 12 weeks
Part 1: Angiotensin II Levels in Plasma During Aliskiren Treatment Period	0.534 fmol/mL Interval 0.223 to 1.28	—	—

PRIMARY outcome

Timeframe: Day 98

Population: All patients who received at least one dose of study drug and had at least one post-baseline assessment of pharmacodynamic data were included in the data analysis.

Interstitial fluid was obtained from subcutaneous adipose and skeletal muscle tissues by microdialysis using the zero-flow method to determine Ang II concentration.

Outcome measures

Measure	Part 1: Placebo/Aliskiren/Amlodipine n=10 Participants Part 1, Period 1: After a 1-2 weeks initial washout period, all eligible patients underwent a two week placebo run-in phase. Part 1 , Period 2: All eligible patients received 4 week treatment of 300 mg aliskiren o.d.. Part 1, Period 3: All patients received 5 mg amlodipine o.d.. The length of the amlodipine period varied from 4 to 7 weeks.	Amlodipine Part 2, Double Blind Period: Eligible randomized patients received amlodipine 5 mg o.d. and aliskiren placebo o.d. for 12 weeks	Amlodipine Part 2, Double Blind: Eligible randomized patients of this arm received amlodipine 5 mg o.d. and aliskiren placebo o.d. for 12 weeks
Part 1: Angiotensin II Levels in Plasma During Amlodipine Treatment Period	2.20 fmol/mL Interval 0.88 to 5.51	—	—

PRIMARY outcome

Timeframe: Day 42

Population: All patients who received at least one dose of study drug and had at least one post-baseline assessment of pharmacodynamic data were included in the data analysis.

Renin concentrations from plasma were measured as: plasma renin concentration (PRC), prorenin concentration and total renin concentration (renin + prorenin concentration).

Outcome measures

Measure	Part 1: Placebo/Aliskiren/Amlodipine n=10 Participants Part 1, Period 1: After a 1-2 weeks initial washout period, all eligible patients underwent a two week placebo run-in phase. Part 1 , Period 2: All eligible patients received 4 week treatment of 300 mg aliskiren o.d.. Part 1, Period 3: All patients received 5 mg amlodipine o.d.. The length of the amlodipine period varied from 4 to 7 weeks.	Amlodipine Part 2, Double Blind Period: Eligible randomized patients received amlodipine 5 mg o.d. and aliskiren placebo o.d. for 12 weeks	Amlodipine Part 2, Double Blind: Eligible randomized patients of this arm received amlodipine 5 mg o.d. and aliskiren placebo o.d. for 12 weeks
Part 1: Renin Concentrations From Plasma During Aliskiren Treatment Period Plasma Renin Concentration	22.29 pg/mL Interval 8.98 to 55.32	—	—
Part 1: Renin Concentrations From Plasma During Aliskiren Treatment Period Total Renin Concentration	89.9 pg/mL Interval 52.4 to 154.2	—	—
Part 1: Renin Concentrations From Plasma During Aliskiren Treatment Period Prorenin Concentration	62.1 pg/mL Interval 40.2 to 96.0	—	—

PRIMARY outcome

Timeframe: Day 98

Population: All patients who received at least one dose of study drug and had at least one post-baseline assessment of pharmacodynamic data were included in the data analysis.

Renin concentrations from plasma were measured as plasma renin concentration (PRC), prorenin concentration and total renin concentration (renin + prorenin concentration).

Outcome measures

Measure	Part 1: Placebo/Aliskiren/Amlodipine n=10 Participants Part 1, Period 1: After a 1-2 weeks initial washout period, all eligible patients underwent a two week placebo run-in phase. Part 1 , Period 2: All eligible patients received 4 week treatment of 300 mg aliskiren o.d.. Part 1, Period 3: All patients received 5 mg amlodipine o.d.. The length of the amlodipine period varied from 4 to 7 weeks.	Amlodipine Part 2, Double Blind Period: Eligible randomized patients received amlodipine 5 mg o.d. and aliskiren placebo o.d. for 12 weeks	Amlodipine Part 2, Double Blind: Eligible randomized patients of this arm received amlodipine 5 mg o.d. and aliskiren placebo o.d. for 12 weeks
Part 1: Renin Concentrations From Plasma During Amlodipine Treatment Period Plasma Renin Concentration	7.36 pg/mL Interval 4.24 to 12.8	—	—
Part 1: Renin Concentrations From Plasma During Amlodipine Treatment Period Total Renin Concentration	66.3 pg/mL Interval 49.8 to 88.2	—	—
Part 1: Renin Concentrations From Plasma During Amlodipine Treatment Period Prorenin Concentration	57.9 pg/mL Interval 44.1 to 76.1	—	—

PRIMARY outcome

Timeframe: Day 42

Population: All patients who received at least one dose of study drug and had at least one post-baseline assessment of pharmacodynamic data were included in the data analysis.

Plasma Renin activity (PRC) was measured by a trapping PRA (tPRA) assay.

Outcome measures

Measure	Part 1: Placebo/Aliskiren/Amlodipine n=10 Participants Part 1, Period 1: After a 1-2 weeks initial washout period, all eligible patients underwent a two week placebo run-in phase. Part 1 , Period 2: All eligible patients received 4 week treatment of 300 mg aliskiren o.d.. Part 1, Period 3: All patients received 5 mg amlodipine o.d.. The length of the amlodipine period varied from 4 to 7 weeks.	Amlodipine Part 2, Double Blind Period: Eligible randomized patients received amlodipine 5 mg o.d. and aliskiren placebo o.d. for 12 weeks	Amlodipine Part 2, Double Blind: Eligible randomized patients of this arm received amlodipine 5 mg o.d. and aliskiren placebo o.d. for 12 weeks
Part 1: Renin Activity From Plasma During Aliskiren Treatment Period	0.145 ng/nl/h Interval 0.055 to 0.386	—	—

PRIMARY outcome

Timeframe: Day 98

Population: All patients who received at least one dose of study drug and had at least one post-baseline assessment of pharmacodynamic data were included in the data analysis.

Plasma renin activity (PRC) was measured by a trapping PRA (tPRA) assay.

Outcome measures

Measure	Part 1: Placebo/Aliskiren/Amlodipine n=10 Participants Part 1, Period 1: After a 1-2 weeks initial washout period, all eligible patients underwent a two week placebo run-in phase. Part 1 , Period 2: All eligible patients received 4 week treatment of 300 mg aliskiren o.d.. Part 1, Period 3: All patients received 5 mg amlodipine o.d.. The length of the amlodipine period varied from 4 to 7 weeks.	Amlodipine Part 2, Double Blind Period: Eligible randomized patients received amlodipine 5 mg o.d. and aliskiren placebo o.d. for 12 weeks	Amlodipine Part 2, Double Blind: Eligible randomized patients of this arm received amlodipine 5 mg o.d. and aliskiren placebo o.d. for 12 weeks
Part 1: Renin Activity From Plasma During Amlodipine Treatment Period	0.670 ng/nl/h Interval 0.269 to 1.672	—	—

PRIMARY outcome

Timeframe: Placebo Baseline (Day 14), Active Treatment (Day 98)

Population: Total 40 completed subjects needed to have a power of 80% in detecting a significant difference between treatment groups. Due to early termination, the study was limited by a small sample size; hence, the planned analysis was not done.

Interstitial fluid was obtained from subcutaneous adipose and skeletal muscle tissues by microdialysis using the zero-flow method to determine Ang II concentration.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Placebo Baseline (Day 14), Active Treatment (Day 98)

Population: Total 40 completed subjects needed to have a power of 80% in detecting a significant difference between treatment groups. Due to early termination, the study was limited by a small sample size; hence, the planned analysis was not done.

Plasma Ang II was measured prior to and 1 hour after the Insulin modified-frequently sampled intravenous glucose tolerance test (IM-FSIGT) during placebo treatment (Days 14) and active treatment(Day 98).

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Day 98

Population: Total 40 completed subjects needed to have a power of 80% in detecting a significant difference between treatment groups. Due to early termination, the study was limited by a small sample size; hence, the planned analysis was not done.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Day 98

Population: Total 40 completed subjects needed to have a power of 80% in detecting a significant difference between treatment groups. Due to early termination, the study was limited by a small sample size; hence, the planned analysis was not done.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 14 and Day 98

Population: Total 40 completed subjects needed to have a power of 80% in detecting a significant difference between treatment groups. Due to early termination, the study was limited by a small sample size; hence, the planned analysis was not done.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Placebo Baseline (Day 14), Active Treatment (Day 98)

Population: Total 40 completed subjects needed to have a power of 80% in detecting a significant difference between treatment groups. Due to early termination, the study was limited by a small sample size; hence, the planned analysis was not done.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Placebo Baseline (Day 14), Active Treatment (Day 98)

Population: Total 40 completed subjects needed to have a power of 80% in detecting a significant difference between treatment groups. Due to early termination, the study was limited by a small sample size; hence, the planned analysis was not done.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Placebo Baseline (Day 14), Active Treatment (Day 98)

Population: Total 40 completed subjects needed to have a power of 80% in detecting a significant difference between treatment groups. Due to early termination, the study was limited by a small sample size; hence, the planned analysis was not done.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Placebo Baseline (Day 14), Active Treatment (Day 98)

Population: Total 40 completed subjects needed to have a power of 80% in detecting a significant difference between treatment groups. Due to early termination, the study was limited by a small sample size; hence, the planned analysis was not done.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 98 days

Population: The safety population consisted of all patients who received at least one dose of study drug with at least one post-baseline safety assessment. Patients were analyzed according to treatment received.

Outcome measures

Measure	Part 1: Placebo/Aliskiren/Amlodipine n=36 Participants Part 1, Period 1: After a 1-2 weeks initial washout period, all eligible patients underwent a two week placebo run-in phase. Part 1 , Period 2: All eligible patients received 4 week treatment of 300 mg aliskiren o.d.. Part 1, Period 3: All patients received 5 mg amlodipine o.d.. The length of the amlodipine period varied from 4 to 7 weeks.	Amlodipine n=8 Participants Part 2, Double Blind Period: Eligible randomized patients received amlodipine 5 mg o.d. and aliskiren placebo o.d. for 12 weeks	Amlodipine n=8 Participants Part 2, Double Blind: Eligible randomized patients of this arm received amlodipine 5 mg o.d. and aliskiren placebo o.d. for 12 weeks
Part 2: Number of Participants With Reported Any Adverse Events, Serious Adverse Events and Death Adverse event	9 Participants	2 Participants	3 Participants
Part 2: Number of Participants With Reported Any Adverse Events, Serious Adverse Events and Death Serious Adverse Event	1 Participants	0 Participants	0 Participants
Part 2: Number of Participants With Reported Any Adverse Events, Serious Adverse Events and Death Death	0 Participants	0 Participants	0 Participants

Adverse Events

Part 1: Aliskiren

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Part 1: Amlodipine

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Part 2: Placebo run-in Period

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Part 2: Aliskiren

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Part 2: Amlodipine

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Measure	Part 1: Aliskiren n=10 participants at risk All eligible patients received 4 week treatment of 300 mg aliskiren o.d..	Part 1: Amlodipine n=10 participants at risk All patients received 5 mg amlodipine o.d.. The length of the amlodipine period varied from 4 to 7 weeks.	Part 2: Placebo run-in Period n=36 participants at risk After confirming study eligibility based on inclusion and exclusion criteria, patients will undergo a two week single-blind placebo run-in phase.	Part 2: Aliskiren n=8 participants at risk Eligible randomized patients of this arm received aliskiren 300 mg tablet o.d. and amlodipine placebo capsule o.d. for 12 weeks	Part 2: Amlodipine n=8 participants at risk Double Blind Period: Eligible randomized patients of this arm received amlodipine 5 mg o.d. and aliskiren placebo o.d. for 12 weeks
Musculoskeletal and connective tissue disorders MUSCLE HAEMORRHAGE	10.0% 1/10 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/10 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/36 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/8 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/8 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.
Vascular disorders HYPERTENSIVE CRISIS	0.00% 0/10 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/10 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	2.8% 1/36 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/8 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/8 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.

Other adverse events

Measure	Part 1: Aliskiren n=10 participants at risk All eligible patients received 4 week treatment of 300 mg aliskiren o.d..	Part 1: Amlodipine n=10 participants at risk All patients received 5 mg amlodipine o.d.. The length of the amlodipine period varied from 4 to 7 weeks.	Part 2: Placebo run-in Period n=36 participants at risk After confirming study eligibility based on inclusion and exclusion criteria, patients will undergo a two week single-blind placebo run-in phase.	Part 2: Aliskiren n=8 participants at risk Eligible randomized patients of this arm received aliskiren 300 mg tablet o.d. and amlodipine placebo capsule o.d. for 12 weeks	Part 2: Amlodipine n=8 participants at risk Double Blind Period: Eligible randomized patients of this arm received amlodipine 5 mg o.d. and aliskiren placebo o.d. for 12 weeks
Gastrointestinal disorders DIARRHOEA	0.00% 0/10 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	10.0% 1/10 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/36 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/8 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	12.5% 1/8 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.
Gastrointestinal disorders DRY MOUTH	0.00% 0/10 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/10 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/36 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	12.5% 1/8 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/8 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.
General disorders IRRITABILITY	0.00% 0/10 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/10 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/36 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	12.5% 1/8 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/8 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.
Infections and infestations NASOPHARYNGITIS	20.0% 2/10 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	20.0% 2/10 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/36 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/8 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/8 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.
Infections and infestations RHINITIS	10.0% 1/10 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/10 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/36 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/8 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/8 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.
Injury, poisoning and procedural complications CONTUSION	0.00% 0/10 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/10 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/36 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/8 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	12.5% 1/8 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.
Injury, poisoning and procedural complications MUSCLE STRAIN	10.0% 1/10 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/10 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/36 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/8 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/8 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.
Injury, poisoning and procedural complications POST PROCEDURAL HAEMATOMA	10.0% 1/10 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/10 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/36 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/8 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/8 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.
Investigations WEIGHT INCREASED	0.00% 0/10 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/10 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/36 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	12.5% 1/8 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/8 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.
Nervous system disorders HEADACHE	10.0% 1/10 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/10 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	2.8% 1/36 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	12.5% 1/8 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/8 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.
Nervous system disorders PARAESTHESIA	0.00% 0/10 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/10 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/36 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	12.5% 1/8 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/8 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.
Psychiatric disorders INSOMNIA	0.00% 0/10 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/10 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/36 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	12.5% 1/8 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/8 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.
Renal and urinary disorders DYSURIA	0.00% 0/10 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/10 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/36 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/8 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	12.5% 1/8 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.
Reproductive system and breast disorders ERECTILE DYSFUNCTION	0.00% 0/10 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/10 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/36 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	12.5% 1/8 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/8 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.
Respiratory, thoracic and mediastinal disorders COUGH	20.0% 2/10 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	10.0% 1/10 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/36 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/8 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/8 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.
Skin and subcutaneous tissue disorders PSORIASIS	0.00% 0/10 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/10 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/36 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	0.00% 0/8 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.	12.5% 1/8 The Safety Population consisted of all patients that received at least one dose of study drug with at least one post-baseline safety assessment. In Part 1 of the study, no events were reported in period 1 when patients received placebo.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Results disclosure agreements

• Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
• Publication restrictions are in place

Restriction type: OTHER