Hypertension, Abdominal Obesity
Conditions
Keywords
Aliskiren, Renin-Angiotensin System (RAS), Hypertension, Abdominal obesity
Brief summary
Part 1 determined: aliskiren, amlodipine and angiotensin II concentrations in interstitial fluid of fat and skeletal muscle; aliskiren and angiotensin II concentrations, and renin activity and concentration in fat and skeletal muscle tissues (biopsies); aliskiren, amlodipine and angiotensin II concentrations, and renin activity and concentration in plasma. Part 2 investigated the potential for aliskiren to modulate renin-angiotensin-aldosterone system (RAAS) activity, and lipid/carbohydrate metabolism in adipose and skeletal muscle tissue in obese patients with hypertension in comparison to amlodipine.
Interventions
DRUGAliskiren
300 mg tablet once daily
DRUGAmlodipine
5 mg capsule once daily
Matching placebo of aliskiren 300 mg tablet
Matching placebo of amlodipine 5 mg capsule
Sponsors
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
PART 1: * Male and female patients 20 to 65 years of age with a diagnosis of hypertension and with abdominal obesity (waist circumference ≥ 102 cm in men and ≥ 88 cm in women) * For patients with a history of treated hypertension, mean sitting systolic blood pressure (msSBP)/ mean sitting diastolic blood pressure (msDBP) had to be ≥ 120/80 mmHg and ≤ 160/100 mm Hg. For patients with newly diagnosed, untreated hypertension msSBP/msDBP had to be ≥ 135/85 mmHg and ≤ 160/100 mm Hg * Pulse rate 40 - 90 bpm PART 2: * Male and female patients 18 to 65 years of age , with a diagnosis of hypertension and with abdominal obesity (waist circumference ≥ 102 cm in men and ≥ 88 cm in women) * Systolic and diastolic blood pressure and pulse rate were assessed after the patient had rested for at least five (5) minutes. Vital signs had to be within the following ranges: 1. Patients with history of treated hypertension: msSBP/msDBP ≥ 135/85 mmHg and \< 160/100 mmHg at baseline 2. Patients with newly diagnosed, untreated hypertension: msSBP/msDBP ≥ 135/85 mmHg and \< 160/100 mmHg at screening and baseline.
Exclusion criteria
PART 1 * Hypertension Grade 2 (msSBP ≥ 160 mmHg) or Grade 3 (msDBP ≥ 110 mmHg and/or msSBP ≥ 180 mmHg) WHO classification * Current treatment with three or more antihypertensive drugs. PART 2 * Hypertension Grade 2 (msSBP ≥ 160 and/or msDBP ≥ 100 mmHg). * Current treatment with three or more antihypertensive drugs. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 2: Plasma Renin Concentration (PRC) Levels During Double Blind Treatment Period | Day 98 | — |
| Part 1: Renin Concentrations From Plasma During Amlodipine Treatment Period | Day 98 | Renin concentrations from plasma were measured as plasma renin concentration (PRC), prorenin concentration and total renin concentration (renin + prorenin concentration). |
| Part 1: Renin Activity From Plasma During Aliskiren Treatment Period | Day 42 | Plasma Renin activity (PRC) was measured by a trapping PRA (tPRA) assay. |
| Part 1: Renin Activity From Plasma During Amlodipine Treatment Period | Day 98 | Plasma renin activity (PRC) was measured by a trapping PRA (tPRA) assay. |
| Part 2: Change From Baseline in Angiotensin II Levels in Interstitial Fluid of Fat and Skeletal Muscle (Microdialysis) During Double Blind Treatment Period | Placebo Baseline (Day 14), Active Treatment (Day 98) | Interstitial fluid was obtained from subcutaneous adipose and skeletal muscle tissues by microdialysis using the zero-flow method to determine Ang II concentration. |
| Part 2: Change From Baseline in Plasma Angiotensin II Levels During Double Blind Treatment Period | Placebo Baseline (Day 14), Active Treatment (Day 98) | 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). |
| Part 2: Plasma Renin Activity (PRA) Concentration During Double Blind Treatment Period | Day 98 | — |
| Part 1: Angiotensin II Levels in Plasma During Amlodipine Treatment Period | Day 98 | Interstitial fluid was obtained from subcutaneous adipose and skeletal muscle tissues by microdialysis using the zero-flow method to determine Ang II concentration. |
| Part 1: Aliskiren Concentrations From Interstitial Fluid (Microdialysis)at the End of Aliskiren Treatment Period | Day 42 | 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). |
| Part 1: Amlodipine Concentrations From Interstitial Fluid (Microdialysis) at the End of Amlodipine Treatment Period | Day 98 | 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). |
| Part 1: Angiotensin II Levels in Interstitial Fluid of Fat and Skeletal Muscle (Microdialysis) During Aliskiren Treatment Period | Day 42 | Interstitial fluid was obtained from subcutaneous adipose and skeletal muscle tissues by microdialysis using the zero-flow method to determine Ang II concentration. |
| Part 1: Angiotensin II Levels in Interstitial Fluid of Fat and Skeletal Muscle (Microdialysis) During Amlodipine Treatment Period | Day 98 | Interstitial fluid was obtained from subcutaneous adipose and skeletal muscle tissues by microdialysis using the zero-flow method to determine Ang II concentration. |
| Part 1: Aliskiren Concentrations From Tissue at the End of Aliskiren Treatment Period | Day 42 | 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). |
| Part 1: Angiotensin II Levels From Tissue During Aliskiren Treatment Period | Day 42 | Biopsies were taken from abdominal adipose and skeletal muscle tissue to determine Ang II concentration. |
| Part 1: Renin Activity and Concentrations From Adipose and Skeletal Tissues During Aliskiren Treatment Period | Day 42 | — |
| Part 1: Aliskiren Concentrations From Plasma at the End of Aliskiren Treatment Period | Day 42 | 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). |
| Part 1: Amlodipine Concentrations From Plasma at the End of Amlodipine Treatment Period | Day 98 | 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). |
| Part 1: Angiotensin II Levels in Plasma During Aliskiren Treatment Period | Day 42 | Interstitial fluid was obtained from subcutaneous adipose and skeletal muscle tissues by microdialysis using the zero-flow method to determine Ang II concentration. |
| Part 1: Renin Concentrations From Plasma During Aliskiren Treatment Period | Day 42 | Renin concentrations from plasma were measured as: plasma renin concentration (PRC), prorenin concentration and total renin concentration (renin + prorenin concentration). |
Secondary
| Measure | Time frame |
|---|---|
| Part 2: Change From Baseline in Official Blood Pressure | Placebo Baseline (Day 14), Active Treatment (Day 98) |
| Part 2: Renin Activity and Concentration of Aliskiren and Amlodipine in Fat and Skeletal Muscle Interstitial Fluid | Placebo Baseline (Day 14), Active Treatment (Day 98) |
| Part 2: Change From Baseline in Peripheral Insulin Sensitivity in Response to Insulin Modified Frequently Sampled Intravenous Glucose Test [IM-FSIGT]for Each Tissue (Adipose or Skeletal Muscle) | Placebo Baseline (Day 14), Active Treatment (Day 98) |
| Part 2: Change From Baseline in Mitochondrial Mass in Subcutaneous Fat and Skeletal Muscle (Tissue Biopsies) | Placebo Baseline (Day 14), Active Treatment (Day 98) |
| Part 2: Number of Participants With Reported Any Adverse Events, Serious Adverse Events and Death | 98 days |
| Part 2: Microdialysis Metabolic Analytes in Response to Insulin Modified Frequently Sampled Intravenous Glucose Test [IM-FSIGT]for Each Tissue (Adipose or Skeletal Muscle) | Day 14 and Day 98 |
Countries
Germany
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Placebo/Aliskiren/Amlodipine 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. | 10 |
| Part 2, Double Blind Period: Aliskiren Eligible randomized patients received aliskiren 300 mg tablet o.d. and amlodipine placebo capsule o.d. for 12 weeks | 8 |
| Part 2, Double Blind: Amlodipine Eligible randomized patients received amlodipine 5 mg o.d. and aliskiren placebo o.d. for 12 weeks | 8 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| 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 |
| Part 2: Placebo Run-in (2 Weeks) | Adverse Event | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | Part 1: Placebo/Aliskiren/Amlodipine | Part 2, Double Blind Period: Aliskiren | Part 2, Double Blind: Amlodipine | Total |
|---|---|---|---|---|
| Age, Continuous Part 1, Open Label | 46 years STANDARD_DEVIATION 7.5 | NA years | NA years | 46 years STANDARD_DEVIATION 7.5 |
| Age, Continuous Part 2, Double blind | NA years | 46.0 years STANDARD_DEVIATION 10.92 | 49.4 years STANDARD_DEVIATION 10.53 | 47.7 years STANDARD_DEVIATION 10.17 |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 2 Participants | 6 Participants |
| Sex: Female, Male Male | 8 Participants | 6 Participants | 6 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 10 | 3 / 10 | 1 / 36 | 2 / 8 | 3 / 8 |
| serious Total, serious adverse events | 1 / 10 | 0 / 10 | 1 / 36 | 0 / 8 | 0 / 8 |
Outcome results
Primary
Part 1: Aliskiren Concentrations From Interstitial Fluid (Microdialysis)at the End of Aliskiren Treatment Period
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).
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Placebo/Aliskiren/Amlodipine | 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: Placebo/Aliskiren/Amlodipine | 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
Part 1: Aliskiren Concentrations From Plasma at the End of Aliskiren Treatment Period
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).
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Placebo/Aliskiren/Amlodipine | Part 1: Aliskiren Concentrations From Plasma at the End of Aliskiren Treatment Period | 8.38 ng/mL | Standard Deviation 4.41 |
Primary
Part 1: Aliskiren Concentrations From Tissue at the End of Aliskiren Treatment Period
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).
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Placebo/Aliskiren/Amlodipine | 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: Placebo/Aliskiren/Amlodipine | 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
Part 1: Amlodipine Concentrations From Interstitial Fluid (Microdialysis) at the End of Amlodipine Treatment Period
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).
Time frame: Day 98
Population: Zero flow concentrations from microdialysates could not be derived by linear regression because of missing data due to inadequate sample volumes.
Primary
Part 1: Amlodipine Concentrations From Plasma at the End of Amlodipine Treatment Period
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).
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Placebo/Aliskiren/Amlodipine | Part 1: Amlodipine Concentrations From Plasma at the End of Amlodipine Treatment Period | 7.78 ng/mL | Standard Deviation 3.61 |
Primary
Part 1: Angiotensin II Levels From Tissue During Aliskiren Treatment Period
Biopsies were taken from abdominal adipose and skeletal muscle tissue to determine Ang II concentration.
Time frame: 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.
Primary
Part 1: Angiotensin II Levels in Interstitial Fluid of Fat and Skeletal Muscle (Microdialysis) During Aliskiren Treatment Period
Interstitial fluid was obtained from subcutaneous adipose and skeletal muscle tissues by microdialysis using the zero-flow method to determine Ang II concentration.
Time frame: Day 42
Population: Due to technical limitations, zero flow concentrations could not be derived for Ang II.
Primary
Part 1: Angiotensin II Levels in Interstitial Fluid of Fat and Skeletal Muscle (Microdialysis) During Amlodipine Treatment Period
Interstitial fluid was obtained from subcutaneous adipose and skeletal muscle tissues by microdialysis using the zero-flow method to determine Ang II concentration.
Time frame: Day 98
Population: Due to technical limitations, zero flow concentrations could not be derived for Ang II.
Primary
Part 1: Angiotensin II Levels in Plasma During Aliskiren Treatment Period
Interstitial fluid was obtained from subcutaneous adipose and skeletal muscle tissues by microdialysis using the zero-flow method to determine Ang II concentration.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part 1: Placebo/Aliskiren/Amlodipine | Part 1: Angiotensin II Levels in Plasma During Aliskiren Treatment Period | 0.534 fmol/mL |
Primary
Part 1: Angiotensin II Levels in Plasma During Amlodipine Treatment Period
Interstitial fluid was obtained from subcutaneous adipose and skeletal muscle tissues by microdialysis using the zero-flow method to determine Ang II concentration.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part 1: Placebo/Aliskiren/Amlodipine | Part 1: Angiotensin II Levels in Plasma During Amlodipine Treatment Period | 2.20 fmol/mL |
Primary
Part 1: Renin Activity and Concentrations From Adipose and Skeletal Tissues During Aliskiren Treatment Period
Time frame: 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.
Primary
Part 1: Renin Activity From Plasma During Aliskiren Treatment Period
Plasma Renin activity (PRC) was measured by a trapping PRA (tPRA) assay.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part 1: Placebo/Aliskiren/Amlodipine | Part 1: Renin Activity From Plasma During Aliskiren Treatment Period | 0.145 ng/nl/h |
Primary
Part 1: Renin Activity From Plasma During Amlodipine Treatment Period
Plasma renin activity (PRC) was measured by a trapping PRA (tPRA) assay.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part 1: Placebo/Aliskiren/Amlodipine | Part 1: Renin Activity From Plasma During Amlodipine Treatment Period | 0.670 ng/nl/h |
Primary
Part 1: Renin Concentrations From Plasma During Aliskiren Treatment Period
Renin concentrations from plasma were measured as: plasma renin concentration (PRC), prorenin concentration and total renin concentration (renin + prorenin concentration).
Time frame: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part 1: Placebo/Aliskiren/Amlodipine | Part 1: Renin Concentrations From Plasma During Aliskiren Treatment Period | Plasma Renin Concentration | 22.29 pg/mL |
| Part 1: Placebo/Aliskiren/Amlodipine | Part 1: Renin Concentrations From Plasma During Aliskiren Treatment Period | Total Renin Concentration | 89.9 pg/mL |
| Part 1: Placebo/Aliskiren/Amlodipine | Part 1: Renin Concentrations From Plasma During Aliskiren Treatment Period | Prorenin Concentration | 62.1 pg/mL |
Primary
Part 1: Renin Concentrations From Plasma During Amlodipine Treatment Period
Renin concentrations from plasma were measured as plasma renin concentration (PRC), prorenin concentration and total renin concentration (renin + prorenin concentration).
Time frame: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part 1: Placebo/Aliskiren/Amlodipine | Part 1: Renin Concentrations From Plasma During Amlodipine Treatment Period | Plasma Renin Concentration | 7.36 pg/mL |
| Part 1: Placebo/Aliskiren/Amlodipine | Part 1: Renin Concentrations From Plasma During Amlodipine Treatment Period | Total Renin Concentration | 66.3 pg/mL |
| Part 1: Placebo/Aliskiren/Amlodipine | Part 1: Renin Concentrations From Plasma During Amlodipine Treatment Period | Prorenin Concentration | 57.9 pg/mL |
Primary
Part 2: Change From Baseline in Angiotensin II Levels in Interstitial Fluid of Fat and Skeletal Muscle (Microdialysis) During Double Blind Treatment Period
Interstitial fluid was obtained from subcutaneous adipose and skeletal muscle tissues by microdialysis using the zero-flow method to determine Ang II concentration.
Time frame: 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.
Primary
Part 2: Change From Baseline in Plasma Angiotensin II Levels During Double Blind Treatment Period
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).
Time frame: 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.
Primary
Part 2: Plasma Renin Activity (PRA) Concentration During Double Blind Treatment Period
Time frame: 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.
Primary
Part 2: Plasma Renin Concentration (PRC) Levels During Double Blind Treatment Period
Time frame: 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.
Secondary
Part 2: Change From Baseline in Mitochondrial Mass in Subcutaneous Fat and Skeletal Muscle (Tissue Biopsies)
Time frame: 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.
Secondary
Part 2: Change From Baseline in Official Blood Pressure
Time frame: 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.
Secondary
Part 2: Change From Baseline in Peripheral Insulin Sensitivity in Response to Insulin Modified Frequently Sampled Intravenous Glucose Test [IM-FSIGT]for Each Tissue (Adipose or Skeletal Muscle)
Time frame: 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.
Secondary
Part 2: Microdialysis Metabolic Analytes in Response to Insulin Modified Frequently Sampled Intravenous Glucose Test [IM-FSIGT]for Each Tissue (Adipose or Skeletal Muscle)
Time frame: 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.
Secondary
Part 2: Number of Participants With Reported Any Adverse Events, Serious Adverse Events and Death
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: Placebo/Aliskiren/Amlodipine | Part 2: Number of Participants With Reported Any Adverse Events, Serious Adverse Events and Death | Serious Adverse Event | 1 Participants |
| Part 1: Placebo/Aliskiren/Amlodipine | Part 2: Number of Participants With Reported Any Adverse Events, Serious Adverse Events and Death | Adverse event | 9 Participants |
| Part 1: Placebo/Aliskiren/Amlodipine | Part 2: Number of Participants With Reported Any Adverse Events, Serious Adverse Events and Death | Death | 0 Participants |
| Amlodipine | Part 2: Number of Participants With Reported Any Adverse Events, Serious Adverse Events and Death | Serious Adverse Event | 0 Participants |
| Amlodipine | Part 2: Number of Participants With Reported Any Adverse Events, Serious Adverse Events and Death | Adverse event | 2 Participants |
| Amlodipine | Part 2: Number of Participants With Reported Any Adverse Events, Serious Adverse Events and Death | Death | 0 Participants |
| Amlodipine | Part 2: Number of Participants With Reported Any Adverse Events, Serious Adverse Events and Death | Adverse event | 3 Participants |
| Amlodipine | Part 2: Number of Participants With Reported Any Adverse Events, Serious Adverse Events and Death | Death | 0 Participants |
| Amlodipine | Part 2: Number of Participants With Reported Any Adverse Events, Serious Adverse Events and Death | Serious Adverse Event | 0 Participants |
Secondary
Part 2: Renin Activity and Concentration of Aliskiren and Amlodipine in Fat and Skeletal Muscle Interstitial Fluid
Time frame: 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.