| Primary | Venous Angiotensin II Levels After 12 Weeks of Treatment | Peripheral venous blood was collected after 30 minutes of rest in the sitting position for analysis of biomarkers. Geometric mean ratio to baseline at Week 12 for Venous angiotensin II levels was calculated in patients with decompensated systolic heart failure (SHF) and left ventricular ejection fraction ≤40% at 0 hour pre-dose, 3 hours and 24 hours post-dose. | Pharmacodynamic (PD) Analysis Set: Subjects with any available PD data and no major protocol deviations with impact on PD data. Only patients with a value at both baseline and post-dose are included. In each category "n" indicates patients with observations at that time point. | Posted | | Geometric Mean | 95% Confidence Interval | ratio | | Baseline. 12 Weeks (Day 84, period 2) | | | | ID | Title | Description |
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| OG000 | Aliskiren | In open label run-in phase (period 1), patients started with ramipril 2.5 mg or 5.0 mg capsule once daily (o.d) depending on previous treatment with RAAS blockers and up-titrated to ramipril 10 mg capsule o.d by end of period 1. In double blind phase (Period 2), patients received aliskiren (150 mg once daily) up titrated to 300 mg once daily after 1 week of treatment following a clinical safety patient assessment at the study site and matching placebo of ramipril capsules. | | OG001 | Ramipril | In open label run-in phase (period 1), patients started with ramipril 2.5 mg or 5.0 mg capsule once daily (o.d) depending on previous treatment with RAAS blockers and up-titrated to ramipril 10 mg capsule o.d by end of period 1. In double blind phase (Period 2), patients received ramipril 10 mg capsule o.d and matching placebo of aliskiren tablet. | | OG002 | Aliskiren Plus Ramipril | In open label run-in phase (period 1), patients started with ramipril 2.5 mg or 5.0 mg capsule once daily (o.d) depending on previous treatment with RAAS blockers and up-titrated to ramipril 10 mg capsule o.d by end of period 1. In double blind phase (period 2), patients received ramipril (10 mg once daily capsule) and aliskiren (150 mg once daily tablet) up titrated to 300 mg once daily after 1 week of treatment following a clinical safety patient assessment at the study site. |
| | | Title | Denominators | Categories |
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| 0 Hour pre-dose (n=40, 38, 37) | | | Title | Measurements |
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| - OG0000.91(0.52 to 1.59)
- OG0011.08(0.64 to 1.81)
- OG0020.66(0.37 to 1.18)
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| | 3 hour post-dose (n=40, 38, 38) |
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| Secondary | Biomarker Plasma Renin Concentration (PRC)After 12 Weeks of Treatment | Peripheral venous blood was collected after 30 minutes of rest in the sitting position for analysis of biomarkers. Geometric Mean Ratio to baseline at 12 weeks for PRC was calculated at 0 hour pre-dose. | Pharmacodynamic (PD) Analysis Set: Subjects with any available PD data and no major protocol deviations with impact on PD data. Only patients with a value at both baseline and post-dose are included. | Posted | | Geometric Mean | 95% Confidence Interval | ratio | | Baseline, 12 weeks (84 days, period 2) | | | | ID | Title | Description |
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| OG000 | Aliskiren | In open label run-in phase (period 1), patients started with ramipril 2.5 mg or 5.0 mg capsule once daily (o.d) depending on previous treatment with RAAS blockers and up-titrated to ramipril 10 mg capsule o.d by end of period 1. In double blind phase (Period 2), patients received aliskiren (150 mg once daily) up titrated to 300 mg once daily after 1 week of treatment following a clinical safety patient assessment at the study site and matching placebo of ramipril capsules. | | OG001 | Ramipril | In open label run-in phase (period 1), patients started with ramipril 2.5 mg or 5.0 mg capsule once daily (o.d) depending on previous treatment with RAAS blockers and up-titrated to ramipril 10 mg capsule o.d by end of period 1. In double blind phase (Period 2), patients received ramipril 10 mg capsule o.d and matching placebo of aliskiren tablet. |
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| Secondary | Biomarker Trapping Plasma Renin Activity (tPRA) After 12 Weeks of Treatment | Peripheral venous blood was collected after 30 minutes of rest in the sitting position for analysis of biomarkers. Geometric Mean Ratio to baseline at Week 12 for tPRA was calculated at 0 hour pre-dose, 3 hour and 24 hour post-dose. | Pharmacodynamic (PD) Analysis Set: Subjects with any available PD data and no major protocol deviations with impact on PD data. Only patients with a value at both baseline and post-dose are included. In each category "n" indicates patients with observations at that time point. | Posted | | Geometric Mean | 95% Confidence Interval | ratio | | Baseline,12 weeks (84 days, Period 2) | | | | ID | Title | Description |
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| OG000 | Aliskiren | In open label run-in phase (period 1), patients started with ramipril 2.5 mg or 5.0 mg capsule once daily (o.d) depending on previous treatment with RAAS blockers and up-titrated to ramipril 10 mg capsule o.d by end of period 1. In double blind phase (Period 2), patients received aliskiren (150 mg once daily) up titrated to 300 mg once daily after 1 week of treatment following a clinical safety patient assessment at the study site and matching placebo of ramipril capsules. | | OG001 | Ramipril | In open label run-in phase (period 1), patients started with ramipril 2.5 mg or 5.0 mg capsule once daily (o.d) depending on previous treatment with RAAS blockers and up-titrated to ramipril 10 mg capsule o.d by end of period 1. In double blind phase (Period 2), patients received ramipril 10 mg capsule o.d and matching placebo of aliskiren tablet. |
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| Secondary | Biomarker B-type Natriuretic Peptide (BNP) After 12 Weeks of Treatment | Peripheral venous blood was collected after 30 minutes of rest in the sitting position for analysis of biomarkers. Geometric Mean Ratio to baseline at Week 12 for BNP was calculated at 0 hours pre-dose. | Pharmacodynamic (PD) Analysis Set: Subjects with any available PD data and no major protocol deviations with impact on PD data. Only patients with a value at both baseline and post-dose are included. | Posted | | Geometric Mean | 95% Confidence Interval | ratio | | Baseline, 12 weeks (Day 84 period 2) | | | | ID | Title | Description |
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| OG000 | Aliskiren | In open label run-in phase (period 1), patients started with ramipril 2.5 mg or 5.0 mg capsule once daily (o.d) depending on previous treatment with RAAS blockers and up-titrated to ramipril 10 mg capsule o.d by end of period 1. In double blind phase (Period 2), patients received aliskiren (150 mg once daily) up titrated to 300 mg once daily after 1 week of treatment following a clinical safety patient assessment at the study site and matching placebo of ramipril capsules. | | OG001 | Ramipril | In open label run-in phase (period 1), patients started with ramipril 2.5 mg or 5.0 mg capsule once daily (o.d) depending on previous treatment with RAAS blockers and up-titrated to ramipril 10 mg capsule o.d by end of period 1. In double blind phase (Period 2), patients received ramipril 10 mg capsule o.d and matching placebo of aliskiren tablet. |
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| Secondary | Biomarker Urinary Aldosterone After 12 Weeks of Treatment | 24 hour urine collections were performed. Geometric Mean Ratio to baseline at Week 12 for Urinary aldosterone was calculated 24 hours post-dose. | Pharmacodynamic (PD) Analysis Set: Subjects with any available PD data and no major protocol deviations with impact on PD data. Only patients with a value at both baseline and post-dose are included. | Posted | | Geometric Mean | 95% Confidence Interval | ratio | | Baseline,12 weeks (Day 84 period 2) | | | | ID | Title | Description |
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| OG000 | Aliskiren | In open label run-in phase (period 1), patients started with ramipril 2.5 mg or 5.0 mg capsule once daily (o.d) depending on previous treatment with RAAS blockers and up-titrated to ramipril 10 mg capsule o.d by end of period 1. In double blind phase (Period 2), patients received aliskiren (150 mg once daily) up titrated to 300 mg once daily after 1 week of treatment following a clinical safety patient assessment at the study site and matching placebo of ramipril capsules. | | OG001 | Ramipril | In open label run-in phase (period 1), patients started with ramipril 2.5 mg or 5.0 mg capsule once daily (o.d) depending on previous treatment with RAAS blockers and up-titrated to ramipril 10 mg capsule o.d by end of period 1. In double blind phase (Period 2), patients received ramipril 10 mg capsule o.d and matching placebo of aliskiren tablet. | |
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| Secondary | Pharmacokinetic of Aliskiren: Time to Reach the Maximum Concentration (Tmax) After Drug Administration | Blood samples (2 mL) for the determination of aliskiren concentration in plasma were collected using an indwelling cannula inserted in a forearm vein. Samples were collected at week 12 (day 84): pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose. | All subjects with evaluable PK parameter data and no major protocol deviations with impact on PK data were included in the PK data analysis. | Posted | | Median | Full Range | Hour | | 12 weeks | | | | ID | Title | Description |
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| OG000 | Aliskiren | In open label run-in phase (period 1), patients started with ramipril 2.5 mg or 5.0 mg capsule once daily (o.d) depending on previous treatment with RAAS blockers and up-titrated to ramipril 10 mg capsule o.d by end of period 1. In double blind phase (Period 2), patients received aliskiren (150 mg once daily) up titrated to 300 mg once daily after 1 week of treatment following a clinical safety patient assessment at the study site and matching placebo of ramipril capsules. |
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| Secondary | Pharmacokinetic of Aliskiren: The Observed Maximum Plasma Concentration (Cmax) Following Drug Administration | Blood samples (2 mL) for the determination of aliskiren concentration in plasma were collected using an indwelling cannula inserted in a forearm vein. Samples were collected at week 12 (day 84): pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose. | All subjects with evaluable PK parameter data and no major protocol deviations with impact on PK data were included in the PK data analysis. | Posted | | Mean | Standard Deviation | ng/mL | | 12 weeks | | | | ID | Title | Description |
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| OG000 | Aliskiren | In open label run-in phase (period 1), patients started with ramipril 2.5 mg or 5.0 mg capsule once daily (o.d) depending on previous treatment with RAAS blockers and up-titrated to ramipril 10 mg capsule o.d by end of period 1. In double blind phase (Period 2), patients received aliskiren (150 mg once daily) up titrated to 300 mg once daily after 1 week of treatment following a clinical safety patient assessment at the study site and matching placebo of ramipril capsules. |
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| Secondary | Pharmacokinetic of Aliskiren: The Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau(AUCtau) | Blood samples (2 mL) for the determination of aliskiren concentration in plasma were collected using an indwelling cannula inserted in a forearm vein. Samples were collected at week 12 (day 84): pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose. | All subjects with evaluable PK parameter data and no major protocol deviations with impact on PK data were included in the PK data analysis. | Posted | | Mean | Standard Deviation | hr*ng/mL | | 12 weeks | | | | ID | Title | Description |
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| OG000 | Aliskiren | In open label run-in phase (period 1), patients started with ramipril 2.5 mg or 5.0 mg capsule once daily (o.d) depending on previous treatment with RAAS blockers and up-titrated to ramipril 10 mg capsule o.d by end of period 1. In double blind phase (Period 2), patients received aliskiren (150 mg once daily) up titrated to 300 mg once daily after 1 week of treatment following a clinical safety patient assessment at the study site and matching placebo of ramipril capsules. |
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| Secondary | Pharmacokinetic of Aliskiren: The Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) | Blood samples (2 mL) for the determination of aliskiren concentration in plasma were collected using an indwelling cannula inserted in a forearm vein. Samples were collected at week 12 (day 84): pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose. | All subjects with evaluable PK parameter data and no major protocol deviations with impact on PK data were included in the PK data analysis. | Posted | | Mean | Standard Deviation | hr*ng/mL | | 12 weeks | | | | ID | Title | Description |
|---|
| OG000 | Aliskiren | In open label run-in phase (period 1), patients started with ramipril 2.5 mg or 5.0 mg capsule once daily (o.d) depending on previous treatment with RAAS blockers and up-titrated to ramipril 10 mg capsule o.d by end of period 1. In double blind phase (Period 2), patients received aliskiren (150 mg once daily) up titrated to 300 mg once daily after 1 week of treatment following a clinical safety patient assessment at the study site and matching placebo of ramipril capsules. |
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| Secondary | Pharmacokinetic of Aliskiren: The Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) | Blood samples (2 mL) for the determination of aliskiren concentration in plasma were collected using an indwelling cannula inserted in a forearm vein. Samples were collected at week 12 (day 84): pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose. | All subjects with evaluable PK parameter data and no major protocol deviations with impact on PK data were included in the PK data analysis. | Posted | | Mean | Standard Deviation | hr*ng/mL | | 12 weeks | | | | ID | Title | Description |
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| OG000 | Aliskiren | In open label run-in phase (period 1), patients started with ramipril 2.5 mg or 5.0 mg capsule once daily (o.d) depending on previous treatment with RAAS blockers and up-titrated to ramipril 10 mg capsule o.d by end of period 1. In double blind phase (Period 2), patients received aliskiren (150 mg once daily) up titrated to 300 mg once daily after 1 week of treatment following a clinical safety patient assessment at the study site and matching placebo of ramipril capsules. |
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| Secondary | Pharmacokinetic of Aliskiren: The Terminal Elimination Half-life (T½) | Blood samples (2 mL) for the determination of aliskiren concentration in plasma were collected using an indwelling cannula inserted in a forearm vein. Samples were collected at week 12 (day 84): pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose. | All subjects with evaluable PK parameter data and no major protocol deviations with impact on PK data were included in the PK data analysis. | Posted | | Mean | Standard Deviation | hour | | 12 weeks | | | | ID | Title | Description |
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| OG000 | Aliskiren | In open label run-in phase (period 1), patients started with ramipril 2.5 mg or 5.0 mg capsule once daily (o.d) depending on previous treatment with RAAS blockers and up-titrated to ramipril 10 mg capsule o.d by end of period 1. In double blind phase (Period 2), patients received aliskiren (150 mg once daily) up titrated to 300 mg once daily after 1 week of treatment following a clinical safety patient assessment at the study site and matching placebo of ramipril capsules. |
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