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The study objective was to assess the effect of single and multiple doses of aliskiren on renal plasma flow, glomerular filtration rate and to compare the effects of single and multiple doses of aliskiren versus captopril or irbesartan on renal blood flow, glomerular filtration rate, and retinal blood flow in patients with type 2 diabetes mellitus.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Aliskiren | Experimental | On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received aliskiren 300 mg tablets orally once a day for 14 days. |
|
| Irbesartan | Active Comparator | On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received irbesartan 300 mg tablets orally once a day for 14 days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Aliskiren | Drug | Aliskiren 300 mg tablets |
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| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Renal Plasma Flow (RPF) After a Single Dose of Aliskiren or Irbesartan | Renal plasma flow (RPF) was measured by the clearance of para-aminohippurate (PAH) by autoanalyzer methods. The measure of the single dose effect (SDE) for aliskiren and irbesartan was calculated as Day 2 peak - Day 2 baseline RPF. Baseline RPF was determined as the median of the -10 minute, -5 minute predose and predose (0 hour) values. Peak RPF was obtained using a moving average concept. | Day 2: Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) and 1, 2, 3, 4 and 5 hours post-dose. |
| Change From Baseline to Steady State Trough in Renal Plasma Flow (RPF) After Aliskiren or Irbesartan | Renal plasma flow (RPF) was measured by the clearance of para-aminohippurate (PAH) by autoanalyzer methods. This multiple dose effect at steady state (MDE_SS) was calculated as Day 15 baseline - Day 2 baseline. Baseline RPF was determined as the median of the -10 minute, -5 minute predose and predose (0 hour) values. | Day 2 and Day 15 at Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) . |
| Change From Baseline to Steady State Peak in Renal Plasma Flow (RPF) After Aliskiren or Irbesartan | Renal plasma flow (RPF) was measured by the clearance of para-aminohippurate (PAH) by autoanalyzer methods. This maximum multiple dose effect (MDE_Max) was calculated as Day 15 peak - Day 2 baseline. Baseline RPF was determined as the median of the -10 minute, -5 minute predose and predose (0 hour) values. Peak RPF was obtained using a moving average concept. | Day 2: Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) and Day 15: 1, 2, 3, 4 and 5 hours post-dose. |
| Change From Single Dose Peak to Steady State Peak in Renal Plasma Flow (RPF) After Aliskiren or Irbesartan | Renal plasma flow (RPF) was measured by the clearance of para-aminohippurate (PAH) by autoanalyzer methods. Accumulation of peak effect from single dose to multiple dose (MDE_Acc) was calculated as Day 15 peak - Day 2 peak. Peak RPF was obtained using a moving average concept. |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Renal Plasma Flow (RPF) After a Single Dose of Captopril | Renal plasma flow (RPF) was measured by the clearance of para-aminohippurate (PAH) by autoanalyzer methods. The measure of the single dose effect (SDE) for captopril was calculated as Day 1 peak - Day 1 baseline RPF. Baseline RPF was determined as the median of the -10 minute, -5 minute predose and predose (0 hour) values. Peak RPF was obtained using a moving average concept. |
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Inclusion Criteria:
Exclusion Criteria:
Other protocol-defined inclusion/exclusion criteria may apply.
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| Name | Affiliation | Role |
|---|---|---|
| Novartis | Novartis investigator site | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigator Site | Boston | Massachusetts | 02115 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22002336 | Derived | Hollenberg NK, Fisher ND, Nussberger J, Moukarbel GV, Barkoudah E, Danser AH. Renal responses to three types of renin-angiotensin system blockers in patients with diabetes mellitus on a high-salt diet: a need for higher doses in diabetic patients? J Hypertens. 2011 Dec;29(12):2454-61. doi: 10.1097/HJH.0b013e32834c627a. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Aliskiren | On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received aliskiren 300 mg tablets orally once a day for 14 days. |
| FG001 | Irbesartan | On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received irbesartan 300 mg tablets orally once a day for 14 days. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Aliskiren | On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received aliskiren 300 mg tablets orally once a day for 14 days. |
| BG001 | Irbesartan |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Secondary | Change From Baseline in Renal Plasma Flow (RPF) After a Single Dose of Captopril | Renal plasma flow (RPF) was measured by the clearance of para-aminohippurate (PAH) by autoanalyzer methods. The measure of the single dose effect (SDE) for captopril was calculated as Day 1 peak - Day 1 baseline RPF. Baseline RPF was determined as the median of the -10 minute, -5 minute predose and predose (0 hour) values. Peak RPF was obtained using a moving average concept. | Pharmacodynamics (PD) analysis set consisted of all patients with available PD data and no major protocol deviations with impact on PD data. | Posted | Mean | Standard Deviation | mL/min/1.73m^2 | Day 1: Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) and 1, 2, 3, 4 and 5 hours post-dose. |
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Study duration (14 days) and 30-days follow-up period.
All patients that received at least one dose of study drug were included in the safety analysis set.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Captopril 25 mg | On Day 1 participants received a single oral dose of 25 mg captopril. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| CHEST PAIN | General disorders | MedDRA | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 862-778-8300 |
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| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| D007674 | Kidney Diseases |
| D006973 | Hypertension |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| C446481 | aliskiren |
| D000077405 | Irbesartan |
| D002216 | Captopril |
| ID | Term |
|---|---|
| D001713 | Biphenyl Compounds |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
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| Irbesartan | Drug | Irbesartan 300 mg tablets |
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| Captopril | Drug | Captopril 25 mg tablet |
|
| Day 2 and Day 15: 1, 2, 3, 4 and 5 hours post-dose. |
| Day 1: Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) and 1, 2, 3, 4 and 5 hours post-dose. |
| Change From Baseline in Glomerular Filtration Rate (GFR) After a Single Dose of Captopril | Glomerular filtration rate (GFR) was measured by the clearance of inulin by autoanalyzer methods. The measure of the single dose effect (SDE) for captopril was calculated as Day 1 peak - Day 1 baseline GFR. Baseline GFR was determined as the median of the -10 minute, -5 minute predose and predose (0 hour) values. Peak GFR was obtained using a moving average concept. | Day 1: Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) and 1, 2, 3, 4 and 5 hours post-dose. |
| Change From Baseline in Glomerular Filtration Rate (GFR) After a Single Dose of Aliskiren or Irbesartan | Glomerular filtration rate (GFR) was measured by the clearance of inulin by autoanalyzer methods. The measure of the single dose effect (SDE) for aliskiren and irbesartan was calculated as Day 2 peak - Day 2 baseline GFR. Baseline GFR was determined as the median of the -10 minute, -5 minute predose and predose (0 hour) values. Peak GFR was obtained using a moving average concept. | Day 2: Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) and 1, 2, 3, 4 and 5 hours post-dose. |
| Change From Baseline to Steady State Trough in Glomerular Filtration Rate (GFR) After Aliskiren or Irbesartan | Glomerular filtration rate (GFR) was measured by the clearance of inulin by autoanalyzer methods. This multiple dose effect at steady state (MDE_SS) was calculated as Day 15 baseline - Day 2 baseline GFR. Baseline GFR was determined as the median of the -10 minute, -5 minute predose and predose (0 hour) values. | Day 2 and Day 15 at Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) . |
| Change From Baseline to Steady State Peak in Glomerular Filtration Rate (GFR) After Aliskiren or Irbesartan | Glomerular filtration rate (GFR) was measured by the clearance of inulin by autoanalyzer methods. This maximum multiple dose effect (MDE_Max) was calculated as Day 15 peak - Day 2 baseline GFR. Baseline GFR was determined as the median of the -10 minute, -5 minute predose and predose (0 hour) values. Peak GFR was obtained using a moving average concept. | Day 2: Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) and Day 15: 1, 2, 3, 4 and 5 hours post-dose. |
| Change From Single Dose Peak to Steady State Peak in Glomerular Filtration Rate (GFR) After Aliskiren or Irbesartan | Glomerular filtration rate (GFR) was measured by the clearance of inulin by autoanalyzer methods. Accumulation of peak effect from single dose to multiple dose (MDE_Acc) was calculated as Day 15 peak - Day 2 peak GFR. Peak GFR was obtained using a moving average concept. | Day 2 and Day 15: 1, 2, 3, 4 and 5 hours post-dose. |
| Change in Plasma Renin Concentration (PRC) After Captopril, Aliskiren or Irbesartan | The following plasma renin concentration effects were assessed: The single dose effect (SDE) for captopril, expressed as the ratio to pre-dose measurement on Day 1, = Day 1, 5 hour / Day 1 Baseline. SDE for aliskiren and irbesartan = Day 2, 5 hour / Day 2 Baseline. Steady state trough effect (multiple dose effect at steady state; MDE_SS) = Day 15 Baseline / Day 2 Baseline. Steady State peak effect (maximum multiple dose effect; MDE_Max) = Day 15, 5 hour / Day 2 Baseline. Accumulation of peak effect from single dose to multiple dose (MDE_Acc) = Day 15, 5 hour / Day 2, 5 hour. | Predose (Baseline) and 5 hours post dose on Days 1, 2 and 15. |
| Change in Plasma Pro-renin Concentration After Captopril, Aliskiren or Irbesartan | The following plasma pro-renin concentration effects were assessed: The single dose effect (SDE) for captopril, expressed as the ratio to pre-dose measurement on Day 1, = Day 1, 5 hour / Day 1 Baseline. SDE for aliskiren and irbesartan = Day 2, 5 hour / Day 2 Baseline. Steady state trough effect (multiple dose effect at steady state; MDE_SS) = Day 15 Baseline / Day 2 Baseline. Steady State peak effect (maximum multiple dose effect; MDE_Max) = Day 15, 5 hour / Day 2 Baseline. Accumulation of peak effect from single dose to multiple dose (MDE_Acc) = Day 15, 5 hour / Day 2, 5 hour. | Predose (Baseline) and 5 hours post dose on Days 1, 2 and 15. |
| Change in Plasma Renin Activity (PRA) After Captopril, Aliskiren or Irbesartan | PRA was measured by the trapping method and the following effects assessed: The single dose effect (SDE) for captopril, expressed as the ratio to pre-dose measurement on Day 1, = Day 1, 5 hour / Day 1 baseline. SDE for aliskiren and irbesartan = Day 2, 5 hour / Day 2 baseline. Steady state trough effect (multiple dose effect at steady state; MDE_SS) = Day 15 baseline / Day 2 baseline. Steady State peak effect (maximum multiple dose effect; MDE_Max) = Day 15, 5 hour / Day 2 baseline. Accumulation of peak effect from single dose to multiple dose (MDE_Acc) = Day 15, 5 hour / Day 2, 5 hour. | Predose and 5 hours post dose on Days 1, 2 and 15. |
| Change in Plasma Angiotensin I After Captopril, Aliskiren or Irbesartan | The following angiotensin I effects were assessed: The single dose effect (SDE) for captopril, expressed as the ratio to pre-dose measurement on Day 1, = Day 1, 5 hour / Day 1 Baseline. SDE for aliskiren and irbesartan = Day 2, 5 hour / Day 2 Baseline. Steady state trough effect (multiple dose effect at steady state; MDE_SS) = Day 15 Baseline / Day 2 Baseline. Steady State peak effect (maximum multiple dose effect; MDE_Max) = Day 15, 5 hour / Day 2 Baseline. Accumulation of peak effect from single dose to multiple dose (MDE_Acc) = Day 15, 5 hour / Day 2, 5 hour. | Predose (Baseline) and 5 hours post dose on Days 1, 2 and 15. |
| Change in Plasma Angiotensin II After Captopril, Aliskiren or Irbesartan | The following angiotensin II effects were assessed: The single dose effect (SDE) for captopril, expressed as the ratio to pre-dose measurement on Day 1, = Day 1, 5 hour / Day 1 Baseline. SDE for aliskiren and irbesartan = Day 2, 5 hour / Day 2 Baseline. Steady state trough effect (multiple dose effect at steady state; MDE_SS) = Day 15 Baseline / Day 2 Baseline. Steady State peak effect (maximum multiple dose effect; MDE_Max) = Day 15, 5 hour / Day 2 Baseline. Accumulation of peak effect from single dose to multiple dose (MDE_Acc) = Day 15, 5 hour / Day 2, 5 hour. | Predose (Baseline) and 5 hours post dose on Days 1, 2 and 15. |
| Change in Serum Aldosterone After Captopril, Aliskiren or Irbesartan | The following serum aldosterone effects were assessed: The single dose effect (SDE) for captopril, expressed as the ratio to pre-dose measurement on Day 1, = Day 1, 5 hour / Day 1 Baseline. SDE for aliskiren and irbesartan = Day 2, 5 hour / Day 2 Baseline. Steady state trough effect (multiple dose effect at steady state; MDE_SS) = Day 15 Baseline / Day 2 Baseline. Steady State peak effect (maximum multiple dose effect; MDE_Max) = Day 15, 5 hour / Day 2 Baseline. Accumulation of peak effect from single dose to multiple dose (MDE_Acc) = Day 15, 5 hour / Day 2, 5 hour. | Predose (Baseline) and 5 hours post dose on Days 1, 2 and 15. |
| Change From Baseline in Retinal Blood Flow After Aliskiren or Irbesartan | Retinal blood flow was assessed using the laser Doppler technique. The blood flow in the superior temporal retinal artery in one of the eyes of each study participant was determined. The Single dose effect of aliskiren or irbesartan was measured as the change/difference between Day 2 and baseline measurements. The Multiple dose effect of aliskiren or irbesartan wsas measured as the change/difference between Day 15 and Day 2 measurements | Baseline (Day 1), Day 2 and Day 15. |
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received irbesartan 300 mg tablets orally once a day for 14 days.
| BG002 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| OG001 | Irbesartan | On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received irbesartan 300 mg tablets orally once a day for 14 days. |
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| Secondary | Change From Baseline in Glomerular Filtration Rate (GFR) After a Single Dose of Captopril | Glomerular filtration rate (GFR) was measured by the clearance of inulin by autoanalyzer methods. The measure of the single dose effect (SDE) for captopril was calculated as Day 1 peak - Day 1 baseline GFR. Baseline GFR was determined as the median of the -10 minute, -5 minute predose and predose (0 hour) values. Peak GFR was obtained using a moving average concept. | Pharmacodynamics (PD) analysis set consisted of all patients with available PD data and no major protocol deviations with impact on PD data. Analysis includes patients for whom data were available. | Posted | Mean | Standard Deviation | mL/min/1.73m^2 | Day 1: Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) and 1, 2, 3, 4 and 5 hours post-dose. |
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| Primary | Change From Baseline in Renal Plasma Flow (RPF) After a Single Dose of Aliskiren or Irbesartan | Renal plasma flow (RPF) was measured by the clearance of para-aminohippurate (PAH) by autoanalyzer methods. The measure of the single dose effect (SDE) for aliskiren and irbesartan was calculated as Day 2 peak - Day 2 baseline RPF. Baseline RPF was determined as the median of the -10 minute, -5 minute predose and predose (0 hour) values. Peak RPF was obtained using a moving average concept. | Pharmacodynamics (PD) analysis set consisted of all patients with available PD data and no major protocol deviations with impact on PD data. | Posted | Mean | Standard Deviation | mL/min/1.73m^2 | Day 2: Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) and 1, 2, 3, 4 and 5 hours post-dose. |
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| Primary | Change From Baseline to Steady State Trough in Renal Plasma Flow (RPF) After Aliskiren or Irbesartan | Renal plasma flow (RPF) was measured by the clearance of para-aminohippurate (PAH) by autoanalyzer methods. This multiple dose effect at steady state (MDE_SS) was calculated as Day 15 baseline - Day 2 baseline. Baseline RPF was determined as the median of the -10 minute, -5 minute predose and predose (0 hour) values. | Pharmacodynamics (PD) analysis set consisted of all patients with available PD data and no major protocol deviations with impact on PD data. Analysis includes patients for whom data were available. | Posted | Mean | Standard Deviation | mL/min/1.73m^2 | Day 2 and Day 15 at Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) . |
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| Primary | Change From Baseline to Steady State Peak in Renal Plasma Flow (RPF) After Aliskiren or Irbesartan | Renal plasma flow (RPF) was measured by the clearance of para-aminohippurate (PAH) by autoanalyzer methods. This maximum multiple dose effect (MDE_Max) was calculated as Day 15 peak - Day 2 baseline. Baseline RPF was determined as the median of the -10 minute, -5 minute predose and predose (0 hour) values. Peak RPF was obtained using a moving average concept. | Pharmacodynamics (PD) analysis set consisted of all patients with available PD data and no major protocol deviations with impact on PD data. Analysis includes patients for whom data were available. | Posted | Mean | Standard Deviation | mL/min/1.73m^2 | Day 2: Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) and Day 15: 1, 2, 3, 4 and 5 hours post-dose. |
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| Primary | Change From Single Dose Peak to Steady State Peak in Renal Plasma Flow (RPF) After Aliskiren or Irbesartan | Renal plasma flow (RPF) was measured by the clearance of para-aminohippurate (PAH) by autoanalyzer methods. Accumulation of peak effect from single dose to multiple dose (MDE_Acc) was calculated as Day 15 peak - Day 2 peak. Peak RPF was obtained using a moving average concept. | Pharmacodynamics (PD) analysis set consisted of all patients with available PD data and no major protocol deviations with impact on PD data. Analysis includes patients for whom data were available. | Posted | Mean | Standard Deviation | mL/min/1.73m^2 | Day 2 and Day 15: 1, 2, 3, 4 and 5 hours post-dose. |
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| Secondary | Change From Baseline in Glomerular Filtration Rate (GFR) After a Single Dose of Aliskiren or Irbesartan | Glomerular filtration rate (GFR) was measured by the clearance of inulin by autoanalyzer methods. The measure of the single dose effect (SDE) for aliskiren and irbesartan was calculated as Day 2 peak - Day 2 baseline GFR. Baseline GFR was determined as the median of the -10 minute, -5 minute predose and predose (0 hour) values. Peak GFR was obtained using a moving average concept. | Pharmacodynamics (PD) analysis set consisted of all patients with available PD data and no major protocol deviations with impact on PD data. Analysis includes patients for whom data were available. | Posted | Mean | Standard Deviation | mL/min/1.73m^2 | Day 2: Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) and 1, 2, 3, 4 and 5 hours post-dose. |
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| Secondary | Change From Baseline to Steady State Trough in Glomerular Filtration Rate (GFR) After Aliskiren or Irbesartan | Glomerular filtration rate (GFR) was measured by the clearance of inulin by autoanalyzer methods. This multiple dose effect at steady state (MDE_SS) was calculated as Day 15 baseline - Day 2 baseline GFR. Baseline GFR was determined as the median of the -10 minute, -5 minute predose and predose (0 hour) values. | Pharmacodynamics (PD) analysis set consisted of all patients with available PD data and no major protocol deviations with impact on PD data. Analysis includes patients for whom data were available. | Posted | Mean | Standard Deviation | mL/min/1.73m^2 | Day 2 and Day 15 at Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) . |
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| Secondary | Change From Baseline to Steady State Peak in Glomerular Filtration Rate (GFR) After Aliskiren or Irbesartan | Glomerular filtration rate (GFR) was measured by the clearance of inulin by autoanalyzer methods. This maximum multiple dose effect (MDE_Max) was calculated as Day 15 peak - Day 2 baseline GFR. Baseline GFR was determined as the median of the -10 minute, -5 minute predose and predose (0 hour) values. Peak GFR was obtained using a moving average concept. | Pharmacodynamics (PD) analysis set consisted of all patients with available PD data and no major protocol deviations with impact on PD data. Analysis includes patients for whom data were available. | Posted | Mean | Standard Deviation | mL/min/1.73m^2 | Day 2: Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) and Day 15: 1, 2, 3, 4 and 5 hours post-dose. |
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| Secondary | Change From Single Dose Peak to Steady State Peak in Glomerular Filtration Rate (GFR) After Aliskiren or Irbesartan | Glomerular filtration rate (GFR) was measured by the clearance of inulin by autoanalyzer methods. Accumulation of peak effect from single dose to multiple dose (MDE_Acc) was calculated as Day 15 peak - Day 2 peak GFR. Peak GFR was obtained using a moving average concept. | Pharmacodynamics (PD) analysis set consisted of all patients with available PD data and no major protocol deviations with impact on PD data. Analysis includes patients for whom data were available. | Posted | Mean | Standard Deviation | mL/min/1.73m^2 | Day 2 and Day 15: 1, 2, 3, 4 and 5 hours post-dose. |
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| Secondary | Change in Plasma Renin Concentration (PRC) After Captopril, Aliskiren or Irbesartan | The following plasma renin concentration effects were assessed: The single dose effect (SDE) for captopril, expressed as the ratio to pre-dose measurement on Day 1, = Day 1, 5 hour / Day 1 Baseline. SDE for aliskiren and irbesartan = Day 2, 5 hour / Day 2 Baseline. Steady state trough effect (multiple dose effect at steady state; MDE_SS) = Day 15 Baseline / Day 2 Baseline. Steady State peak effect (maximum multiple dose effect; MDE_Max) = Day 15, 5 hour / Day 2 Baseline. Accumulation of peak effect from single dose to multiple dose (MDE_Acc) = Day 15, 5 hour / Day 2, 5 hour. | PD analysis set. The number of patients with data available included in each analysis is indicated by 'N' [Aliskiren, Irbesartan]. | Posted | Geometric Mean | 95% Confidence Interval | ratio | Predose (Baseline) and 5 hours post dose on Days 1, 2 and 15. |
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| Secondary | Change in Plasma Pro-renin Concentration After Captopril, Aliskiren or Irbesartan | The following plasma pro-renin concentration effects were assessed: The single dose effect (SDE) for captopril, expressed as the ratio to pre-dose measurement on Day 1, = Day 1, 5 hour / Day 1 Baseline. SDE for aliskiren and irbesartan = Day 2, 5 hour / Day 2 Baseline. Steady state trough effect (multiple dose effect at steady state; MDE_SS) = Day 15 Baseline / Day 2 Baseline. Steady State peak effect (maximum multiple dose effect; MDE_Max) = Day 15, 5 hour / Day 2 Baseline. Accumulation of peak effect from single dose to multiple dose (MDE_Acc) = Day 15, 5 hour / Day 2, 5 hour. | PD analysis set. The number of patients with data available included in each analysis is indicated by 'N' [Aliskiren, Irbesartan]. | Posted | Geometric Mean | 95% Confidence Interval | ratio | Predose (Baseline) and 5 hours post dose on Days 1, 2 and 15. |
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| Secondary | Change in Plasma Renin Activity (PRA) After Captopril, Aliskiren or Irbesartan | PRA was measured by the trapping method and the following effects assessed: The single dose effect (SDE) for captopril, expressed as the ratio to pre-dose measurement on Day 1, = Day 1, 5 hour / Day 1 baseline. SDE for aliskiren and irbesartan = Day 2, 5 hour / Day 2 baseline. Steady state trough effect (multiple dose effect at steady state; MDE_SS) = Day 15 baseline / Day 2 baseline. Steady State peak effect (maximum multiple dose effect; MDE_Max) = Day 15, 5 hour / Day 2 baseline. Accumulation of peak effect from single dose to multiple dose (MDE_Acc) = Day 15, 5 hour / Day 2, 5 hour. | PD analysis set. The number of patients with data available included in each analysis is indicated by 'N' [Aliskiren, Irbesartan]. | Posted | Geometric Mean | 95% Confidence Interval | ratio | Predose and 5 hours post dose on Days 1, 2 and 15. |
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| Secondary | Change in Plasma Angiotensin I After Captopril, Aliskiren or Irbesartan | The following angiotensin I effects were assessed: The single dose effect (SDE) for captopril, expressed as the ratio to pre-dose measurement on Day 1, = Day 1, 5 hour / Day 1 Baseline. SDE for aliskiren and irbesartan = Day 2, 5 hour / Day 2 Baseline. Steady state trough effect (multiple dose effect at steady state; MDE_SS) = Day 15 Baseline / Day 2 Baseline. Steady State peak effect (maximum multiple dose effect; MDE_Max) = Day 15, 5 hour / Day 2 Baseline. Accumulation of peak effect from single dose to multiple dose (MDE_Acc) = Day 15, 5 hour / Day 2, 5 hour. | PD analysis set. The number of patients with data available included in each analysis is indicated by 'N' [Aliskiren, Irbesartan]. | Posted | Geometric Mean | 95% Confidence Interval | ratio | Predose (Baseline) and 5 hours post dose on Days 1, 2 and 15. |
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| Secondary | Change in Plasma Angiotensin II After Captopril, Aliskiren or Irbesartan | The following angiotensin II effects were assessed: The single dose effect (SDE) for captopril, expressed as the ratio to pre-dose measurement on Day 1, = Day 1, 5 hour / Day 1 Baseline. SDE for aliskiren and irbesartan = Day 2, 5 hour / Day 2 Baseline. Steady state trough effect (multiple dose effect at steady state; MDE_SS) = Day 15 Baseline / Day 2 Baseline. Steady State peak effect (maximum multiple dose effect; MDE_Max) = Day 15, 5 hour / Day 2 Baseline. Accumulation of peak effect from single dose to multiple dose (MDE_Acc) = Day 15, 5 hour / Day 2, 5 hour. | PD analysis set. The number of patients with data available included in each analysis is indicated by 'N' [Aliskiren, Irbesartan]. | Posted | Geometric Mean | 95% Confidence Interval | ratio | Predose (Baseline) and 5 hours post dose on Days 1, 2 and 15. |
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| Secondary | Change in Serum Aldosterone After Captopril, Aliskiren or Irbesartan | The following serum aldosterone effects were assessed: The single dose effect (SDE) for captopril, expressed as the ratio to pre-dose measurement on Day 1, = Day 1, 5 hour / Day 1 Baseline. SDE for aliskiren and irbesartan = Day 2, 5 hour / Day 2 Baseline. Steady state trough effect (multiple dose effect at steady state; MDE_SS) = Day 15 Baseline / Day 2 Baseline. Steady State peak effect (maximum multiple dose effect; MDE_Max) = Day 15, 5 hour / Day 2 Baseline. Accumulation of peak effect from single dose to multiple dose (MDE_Acc) = Day 15, 5 hour / Day 2, 5 hour. | PD analysis set. The number of patients with data available included in each analysis is indicated by 'N' [Aliskiren, Irbesartan]. | Posted | Geometric Mean | 95% Confidence Interval | ratio | Predose (Baseline) and 5 hours post dose on Days 1, 2 and 15. |
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| Secondary | Change From Baseline in Retinal Blood Flow After Aliskiren or Irbesartan | Retinal blood flow was assessed using the laser Doppler technique. The blood flow in the superior temporal retinal artery in one of the eyes of each study participant was determined. The Single dose effect of aliskiren or irbesartan was measured as the change/difference between Day 2 and baseline measurements. The Multiple dose effect of aliskiren or irbesartan wsas measured as the change/difference between Day 15 and Day 2 measurements | PD analysis set. This assessment was only conducted at sites with available Canon Laser Blood Flowmeter. The number of patients with data available included in each analysis is indicated by 'N' [Aliskiren, Irbesartan]. | Posted | Mean | Standard Deviation | µL/min | Baseline (Day 1), Day 2 and Day 15. |
|
|
|
| 0 |
| 45 |
| 2 |
| 45 |
| EG001 | Aliskiren 300 mg | Starting on Day 2 participants received aliskiren 300 mg tablets orally once a day for 14 days. | 0 | 22 | 5 | 22 |
| EG002 | Irbesartan 300 mg | Starting on Day 2 participants received irbesartan 300 mg tablets orally once a day for 14 days. | 0 | 21 | 5 | 21 |
| BLOOD PRESSURE INCREASED | Investigations | MedDRA | Systematic Assessment |
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| DIZZINESS | Nervous system disorders | MedDRA | Systematic Assessment |
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| HEADACHE | Nervous system disorders | MedDRA | Systematic Assessment |
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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.
| D004700 | Endocrine System Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |
| D013141 | Spiro Compounds |
| D013777 | Tetrazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011083 | Polycyclic Compounds |
| D011392 | Proline |
| D007098 | Imino Acids |
| D000598 | Amino Acids, Cyclic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| Steady State Trough Effect [N= 21, 19] |
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| Steady State Peak Effect [N=21, 19] |
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| Accumulation of Peak Effect [N= 21, 18] |
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| Steady State Trough Effect [N= 21, 19] |
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| Steady State Peak Effect [N=21, 19] |
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| Accumulation of Peak Effect [N= 21, 18] |
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| Steady State Trough Effect [N= 21, 19] |
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| Steady State Peak Effect [N=21, 18] |
|
| Accumulation of Peak Effect [N= 21, 18] |
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| Steady State Trough Effect [N= 21, 19] |
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| Steady State Peak Effect [N=21, 18] |
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| Accumulation of Peak Effect [N= 21, 18] |
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| Steady State Trough Effect [N= 21, 19] |
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| Steady State Peak Effect [N=21, 18] |
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| Accumulation of Peak Effect [N= 21, 18] |
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| Steady State Trough Effect [N= 21, 19] |
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| Steady State Peak Effect [N= 21, 18] |
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| Accumulation of Peak Effect [N= 21, 18] |
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