Heart Failure
Conditions
Keywords
Heart failure,, aliskiren,, furosemide,, diuretic efficacy,, interaction
Brief summary
This study assessed the interaction between single and multiple doses of aliskiren (150 mg and 300 mg) and furosemide (60 mg) in patients with heart failure.
Interventions
DRUGAliskiren 150 mg
Aliskiren 150 mg tablet
DRUGFurosemide 60 mg
Furosemide 60 mg commercially-available tablets
Matching placebo for aliskiren 150 mg and 300 mg
DRUGAliskiren 300 mg
Aliskiren 300 mg tablet
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Systolic or diastolic heart failure, diagnosed with either NYHA functional class II to III at least 3 months prior to screening and on stable medication for at least 12 weeks. * Patients must have met either of the criteria at screening: * Documented left ventricular ejection fraction (LVEF) greater than 20% but lower than 40% OR * Patients with a documented LVEF greater than 40% and with a history of NT-pro-BNP\> 400pg/mL (or BNP \> 100pg/mL) within 12 months of screening.
Exclusion criteria
* Treatment with Angiotensin Receptor Blockers (ARBs), aldosterone receptor antagonists and diuretics (other than furosemide) within 3 weeks of first dose and during the study. Beta blockers were permitted provided the dose was stable for at least 3 weeks before the first dose and remains so throughout the study. * Hypertrophic cardiomyopathy (HCMP). * If a subject is currently treated with furosemide, the dose must be stable for at least 3 weeks before the first dose and the dose must not exceed 60 mg daily * Stable heart failure requiring treatment with both an ACE inhibitor and an ARB or Current acute decompensated heart failure. * Mean sitting systolic blood pressure ≥160 mmHg and/or mean sitting diastolic blood pressure ≥ 100mmHg and/or secondary forms of hypertension. * Persistent sitting systolic blood pressure \<90 mmHg. * History of angioedema. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Diuretic Efficacy Index 1 for Sodium Excretion | 0 to 4 hours | Efficacy of furosemide for sodium excretion (efficacy index 1) was defined by dividing urinary sodium excretion by the urinary excretion of furosemide. Diuretic index 1 for sodium was calculated for the for the total 0 to 4 hour urine collection. |
| Diuretic Efficacy Index 2 for Water Excretion | 0 to 4 hours | Efficacy of furosemide for water excretion (efficacy index 2) was defined by dividing urine volume by the urinary excretion of furosemide.Diuretic index 2 for water was calculated for the 0 to 4 hour fraction urine collection. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Pharmacokinetics (PK) of Furosemide: Time to Reach the Maximum Concentration After Drug Administration (Tmax) | pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post dose | Tmax was directly determined from the raw plasma concentration-time data. |
| Plasma Pharmacokinetics (PK) of Furosemide: Average Steady State Plasma Concentration During Multiple Dosing (Cav,ss) | pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post dose | The average steady-state drug concentration in the plasma, blood, serum, or other body fluids during multiple dosing \[amount x volume-1\]. This was estimated as AUCτ/τ |
| Plasma Pharmacokinetics (PK) of Furosemide: Lowest Plasma Concentration Observed During a Dosing Interval at Steady State (Cmin, ss) | pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 24 hours post dose | The minimum observed steady-state drug concentration in the plasma, blood, serum, or other body fluids at the end of the dosing interval during multiple dosing \[amount x volume-1\] |
| Urine Pharmacokinetics (PK) of Furosemide: Amount of Drug Excreted Into the Urine From Time Zero to 24 Hours After Administration (Ae0-24) | 0 to 4, 4 to 8, 8 to 12 and 12 to 24 hours post dose | The area under the plasma (or serum or blood) concentration-time curve from time zero to 24 h \[mass × time × volume-1\] |
| Urine Pharmacokinetics (PK) of Furosemide: Renal Clearance (CLR) | 0 to 4, 4 to 8, 8 to 12 and 12 to 24 hours post dose | The renal clearance of drug \[volume x time-1\] |
| Plasma Pharmacokinetics (PK) of Furosemide: Area Under the Plasma Concentration-time Curve (AUC) | pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post dose | Pharmacokinetic (PK) parameters were determined from the plasma concentration time profile of furosemide using a non-compartmental method: AUCtau: Area under the plasma concentration-time curve from time zero to the end of the dosing interval AUC (0-24): Area under the plasma concentration-time curve from time zero to 24 hours AUClast: Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration. AUClast was calculated as the sum of linear trapezoids using non-compartmental analysis. AUCinf: Area under the plasma concentration-time curve from time zero to infinity. AUCinf was calculated by adding AUClast and the value obtained from dividing the last measurable plasma concentration by λz, where λz was determined from automated linear regression of the last three time points with non-zero concentrations in the terminal phase of the log-transformed concentration-time profile |
| Urine Sodium and Potassium Excretion Per Treatment at 4 Hours Postdose | 4 hours postdose | Urine was collected 4 hours postdose in all treatment groups for sodium and potassium analysis. Each patient was required to void their bladder before drug administration and at the end 4 hours. |
| Urine Sodium and Potassium Excretion Per Treatment at 8 Hours Postdose | 8 hours postdose | Urine was collected 8 hours postdose in all treatment groups for sodium and potassium analysis. Each patient was required to void their bladder before drug administration and at the end 8 hours. |
| Urine Sodium and Potassium Excretion Per Treatment at 12 Hours Postdose | 12 hours postdose | Urine was collected 12 hours postdose in all treatment groups for sodium and potassium analysis. Each patient was required to void their bladder before drug administration and at the end 12 hours. |
| Urine Sodium and Potassium Excretion Per Treatment at 24 Hours Postdose | 24 hours postdose | Urine was collected 24 hours postdose in all treatment groups for sodium and potassium analysis. Each patient was required to void their bladder before drug administration and at the end 24 hours. |
| Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 0.5 hour pre-dose, 0.5, 1, 2, 4, 8, 12 and 24 hours post dose. | Sitting blood pressure was measured three times at 1 to 2-minute intervals. The mean of the three sitting blood pressure measurements was used as the average of the sitting office blood pressure. The msSBP and msDBP data were analyzed using a mixed effect model with fixed effects from treatment and treatment\*time; random effect from patients and predose as covariate. |
| Creatinine Clearance | 0 to 4, 4 to 8, 8 to 12 and 12 to 24 hours post dose | Creatinine clearance= (Urine creatinine/Serum creatinine) x (Urine volume/(24\*60)). |
| Plasma Pharmacokinetics (PK) of Furosemide: Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax, ss) | pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post dose | Cmax,ss was directly determined from the raw plasma concentration-time data. |
Countries
Germany, Lithuania
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Furosemide (Fu) /Fu+Aliskiren(Alis)150mg/fu+Alis 300mg Treatment period 1 (Day 1 to Day 7): All eligible patients received 60 mg furosemide, 150 mg placebo of aliskiren, and 300 mg placebo aliskiren once daily.
Treatment Period 2 (Day 8 to day 17): Patients received 60 mg furosemide, 150 mg aliskiren and 300 mg placebo once daily.
Treatment Period 3 (Day 18 to day 27): Patients received 60 mg furosemide, 300 mg aliskiren and 150 mg placebo of aliskiren once daily.
Day 28, no study treatment. | 37 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Treatment Period 1 (Day 1 - Day 7) | Administrative problems | 1 |
| Treatment Period 1 (Day 1 - Day 7) | Adverse Event | 1 |
| Treatment Period 2 (Day 8 - Day 17) | Adverse Event | 3 |
| Treatment Period2(Day9-Day27) and Day 28 | Adverse Event | 2 |
| Treatment Period2(Day9-Day27) and Day 28 | Protocol Deviation | 1 |
| Treatment Period2(Day9-Day27) and Day 28 | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Furosemide (Fu) /Fu+Aliskiren(Alis)150mg/fu+Alis 300mg |
|---|---|
| Age Continuous | 59.6 years STANDARD_DEVIATION 11.9 |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 37 | 0 / 33 | 0 / 31 |
| serious Total, serious adverse events | 2 / 37 | 0 / 33 | 0 / 31 |
Outcome results
Primary
Diuretic Efficacy Index 1 for Sodium Excretion
Efficacy of furosemide for sodium excretion (efficacy index 1) was defined by dividing urinary sodium excretion by the urinary excretion of furosemide. Diuretic index 1 for sodium was calculated for the for the total 0 to 4 hour urine collection.
Time frame: 0 to 4 hours
Population: All patients who received at least one dose of study drug and had evaluable pharmacodynamic (PD) data with no major protocol deviation in at least one period were included in the PD analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Furosemide 60 mg + Aliskiren Placebo | Diuretic Efficacy Index 1 for Sodium Excretion | 10.185 mmol/mg | Standard Deviation 4.4568 |
| Furosemide 60 mg+ Single Dose Aliskiren 150mg | Diuretic Efficacy Index 1 for Sodium Excretion | 12.122 mmol/mg | Standard Deviation 6.2867 |
| Furosemide 60 mg + Multiple Dose Aliskiren 150mg | Diuretic Efficacy Index 1 for Sodium Excretion | 13.453 mmol/mg | Standard Deviation 8.3524 |
| Furosemide 60 mg + Multiple Dose Aliskiren 300mg | Diuretic Efficacy Index 1 for Sodium Excretion | 12.858 mmol/mg | Standard Deviation 6.104 |
Primary
Diuretic Efficacy Index 1 for Sodium Excretion
Efficacy of furosemide for sodium excretion (efficacy index 1) was defined by dividing urinary sodium excretion by the urinary excretion of furosemide. Diuretic index 1 for sodium was calculated for the for the total 0 to 24 hour urine collection.
Time frame: 0 to 24 hours
Population: All patients who received at least one dose of study drug and had evaluable pharmacodynamic (PD) data with no major protocol deviation in at least one period were included in the PD analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Furosemide 60 mg + Aliskiren Placebo | Diuretic Efficacy Index 1 for Sodium Excretion | 10.775 mmol/mg | Standard Deviation 5.2486 |
| Furosemide 60 mg+ Single Dose Aliskiren 150mg | Diuretic Efficacy Index 1 for Sodium Excretion | 13.264 mmol/mg | Standard Deviation 6.3535 |
| Furosemide 60 mg + Multiple Dose Aliskiren 150mg | Diuretic Efficacy Index 1 for Sodium Excretion | 13.364 mmol/mg | Standard Deviation 6.1511 |
| Furosemide 60 mg + Multiple Dose Aliskiren 300mg | Diuretic Efficacy Index 1 for Sodium Excretion | 14.747 mmol/mg | Standard Deviation 6.3531 |
Primary
Diuretic Efficacy Index 2 for Water Excretion
Efficacy of furosemide for water excretion (efficacy index 2) was defined by dividing urine volume by the urinary excretion of furosemide.Diuretic index 2 for water was calculated for the 0 to 4 hour fraction and for the total 0 to 24 hour urine collection.
Time frame: 0 to 24 hours
Population: All patients who received at least one dose of study drug and had evaluable PD data with no major protocol deviation in at least one period were included in the PD analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Furosemide 60 mg + Aliskiren Placebo | Diuretic Efficacy Index 2 for Water Excretion | 119.439 mL/mg | Standard Deviation 46.2607 |
| Furosemide 60 mg+ Single Dose Aliskiren 150mg | Diuretic Efficacy Index 2 for Water Excretion | 151.859 mL/mg | Standard Deviation 53.6734 |
| Furosemide 60 mg + Multiple Dose Aliskiren 150mg | Diuretic Efficacy Index 2 for Water Excretion | 154.116 mL/mg | Standard Deviation 40.5598 |
| Furosemide 60 mg + Multiple Dose Aliskiren 300mg | Diuretic Efficacy Index 2 for Water Excretion | 175.112 mL/mg | Standard Deviation 59.4236 |
Primary
Diuretic Efficacy Index 2 for Water Excretion
Efficacy of furosemide for water excretion (efficacy index 2) was defined by dividing urine volume by the urinary excretion of furosemide.Diuretic index 2 for water was calculated for the 0 to 4 hour fraction urine collection.
Time frame: 0 to 4 hours
Population: All patients who received at least one dose of study drug and had evaluable PD data with no major protocol deviation in at least one period were included in the PD analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Furosemide 60 mg + Aliskiren Placebo | Diuretic Efficacy Index 2 for Water Excretion | 90.402 mL/mg | Standard Deviation 34.7866 |
| Furosemide 60 mg+ Single Dose Aliskiren 150mg | Diuretic Efficacy Index 2 for Water Excretion | 109.773 mL/mg | Standard Deviation 50.2433 |
| Furosemide 60 mg + Multiple Dose Aliskiren 150mg | Diuretic Efficacy Index 2 for Water Excretion | 119.239 mL/mg | Standard Deviation 63.3655 |
| Furosemide 60 mg + Multiple Dose Aliskiren 300mg | Diuretic Efficacy Index 2 for Water Excretion | 122.157 mL/mg | Standard Deviation 58.8815 |
Secondary
Creatinine Clearance
Creatinine clearance= (Urine creatinine/Serum creatinine) x (Urine volume/(24\*60)).
Time frame: 0 to 4, 4 to 8, 8 to 12 and 12 to 24 hours post dose
Population: All patients who received at least one dose of study drug and had evaluable PD data with no major protocol deviation in at least one period were included in the PD analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Furosemide 60 mg + Aliskiren Placebo | Creatinine Clearance | 104.745 mL/min | Standard Deviation 38.2884 |
| Furosemide 60 mg+ Single Dose Aliskiren 150mg | Creatinine Clearance | 109.657 mL/min | Standard Deviation 30.0667 |
| Furosemide 60 mg + Multiple Dose Aliskiren 150mg | Creatinine Clearance | 103.841 mL/min | Standard Deviation 28.2845 |
| Furosemide 60 mg + Multiple Dose Aliskiren 300mg | Creatinine Clearance | 105.304 mL/min | Standard Deviation 25.4076 |
Secondary
Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP)
Sitting blood pressure was measured three times at 1 to 2-minute intervals. The mean of the three sitting blood pressure measurements was used as the average of the sitting office blood pressure. The msSBP and msDBP data were analyzed using a mixed effect model with fixed effects from treatment and treatment\*time; random effect from patients and predose as covariate.
Time frame: 0.5 hour pre-dose, 0.5, 1, 2, 4, 8, 12 and 24 hours post dose.
Population: Safety analysis set include subjects that received study drug.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Furosemide 60 mg + Aliskiren Placebo | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 8 hour Postdose (msDBP) | 66.33 mmHg | Standard Error 1.01 |
| Furosemide 60 mg + Aliskiren Placebo | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 2 hour Postdose (msSBP) | 113.61 mmHg | Standard Error 1.64 |
| Furosemide 60 mg + Aliskiren Placebo | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 0.5 hour Postdose (msSBP) | 114.78 mmHg | Standard Error 1.64 |
| Furosemide 60 mg + Aliskiren Placebo | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 8 hour Postdose (msSBP) | 110.75 mmHg | Standard Error 1.66 |
| Furosemide 60 mg + Aliskiren Placebo | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 2 hour Postdose (msDBP) | 68.39 mmHg | Standard Error 1.1 |
| Furosemide 60 mg + Aliskiren Placebo | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 24 hour Postdose (msSBP) | 115.49 mmHg | Standard Error 1.66 |
| Furosemide 60 mg + Aliskiren Placebo | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 4 hour Postdose (msSBP) | 106.50 mmHg | Standard Error 1.64 |
| Furosemide 60 mg + Aliskiren Placebo | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 0.5 hour Postdose (msDBP) | 70.94 mmHg | Standard Error 1 |
| Furosemide 60 mg + Aliskiren Placebo | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 4 hour Postdose (msDBP) | 63.85 mmHg | Standard Error 1 |
| Furosemide 60 mg + Aliskiren Placebo | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 0.5 hour predose (msDBP) | 71.70 mmHg | Standard Error 0.98 |
| Furosemide 60 mg + Aliskiren Placebo | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 12 hour Postdose (msdBP) | 67.86 mmHg | Standard Error 1.01 |
| Furosemide 60 mg + Aliskiren Placebo | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 1 hour Postdose (msSBP) | 115.15 mmHg | Standard Error 1.64 |
| Furosemide 60 mg + Aliskiren Placebo | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 24 hour Postdose (msDBP) | 71.24 mmHg | Standard Error 1.01 |
| Furosemide 60 mg + Aliskiren Placebo | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 12 hour Postdose (msSBP) | 116.99 mmHg | Standard Error 1.66 |
| Furosemide 60 mg + Aliskiren Placebo | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 1 hour Postdose (msDBP) | 71.22 mmHg | Standard Error 1 |
| Furosemide 60 mg + Aliskiren Placebo | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 0.5 predose (msSBP) | 118.26 mmHg | Standard Error 1.62 |
| Furosemide 60 mg+ Single Dose Aliskiren 150mg | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 24 hour Postdose (msSBP) | 116.69 mmHg | Standard Error 1.72 |
| Furosemide 60 mg+ Single Dose Aliskiren 150mg | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 0.5 predose (msSBP) | 117.09 mmHg | Standard Error 1.7 |
| Furosemide 60 mg+ Single Dose Aliskiren 150mg | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 0.5 hour predose (msDBP) | 71.41 mmHg | Standard Error 1.04 |
| Furosemide 60 mg+ Single Dose Aliskiren 150mg | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 0.5 hour Postdose (msDBP) | 69.04 mmHg | Standard Error 1.04 |
| Furosemide 60 mg+ Single Dose Aliskiren 150mg | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 1 hour Postdose (msSBP) | 112.22 mmHg | Standard Error 1.7 |
| Furosemide 60 mg+ Single Dose Aliskiren 150mg | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 1 hour Postdose (msDBP) | 69.04 mmHg | Standard Error 1.04 |
| Furosemide 60 mg+ Single Dose Aliskiren 150mg | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 2 hour Postdose (msSBP) | 109.22 mmHg | Standard Error 1.7 |
| Furosemide 60 mg+ Single Dose Aliskiren 150mg | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 2 hour Postdose (msDBP) | 67.50 mmHg | Standard Error 1.04 |
| Furosemide 60 mg+ Single Dose Aliskiren 150mg | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 4 hour Postdose (msSBP) | 101.84 mmHg | Standard Error 1.7 |
| Furosemide 60 mg+ Single Dose Aliskiren 150mg | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 4 hour Postdose (msDBP) | 62.32 mmHg | Standard Error 1.04 |
| Furosemide 60 mg+ Single Dose Aliskiren 150mg | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 8 hour Postdose (msSBP) | 112.09 mmHg | Standard Error 1.7 |
| Furosemide 60 mg+ Single Dose Aliskiren 150mg | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 8 hour Postdose (msDBP) | 66.94 mmHg | Standard Error 1.04 |
| Furosemide 60 mg+ Single Dose Aliskiren 150mg | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 12 hour Postdose (msSBP) | 116.90 mmHg | Standard Error 1.7 |
| Furosemide 60 mg+ Single Dose Aliskiren 150mg | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 12 hour Postdose (msdBP) | 68.79 mmHg | Standard Error 1.04 |
| Furosemide 60 mg+ Single Dose Aliskiren 150mg | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 24 hour Postdose (msDBP) | 71.66 mmHg | Standard Error 1.05 |
| Furosemide 60 mg+ Single Dose Aliskiren 150mg | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 0.5 hour Postdose (msSBP) | 113.19 mmHg | Standard Error 1.7 |
| Furosemide 60 mg + Multiple Dose Aliskiren 150mg | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 2 hour Postdose (msDBP) | 68.39 mmHg | Standard Error 1.1 |
| Furosemide 60 mg + Multiple Dose Aliskiren 150mg | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 8 hour Postdose (msDBP) | 66.46 mmHg | Standard Error 1.1 |
| Furosemide 60 mg + Multiple Dose Aliskiren 150mg | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 1 hour Postdose (msSBP) | 112.16 mmHg | Standard Error 1.8 |
| Furosemide 60 mg + Multiple Dose Aliskiren 150mg | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 24 hour Postdose (msDBP) | 72.32 mmHg | Standard Error 1.1 |
| Furosemide 60 mg + Multiple Dose Aliskiren 150mg | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 12 hour Postdose (msSBP) | 115.16 mmHg | Standard Error 1.8 |
| Furosemide 60 mg + Multiple Dose Aliskiren 150mg | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 0.5 hour Postdose (msDBP) | 69.86 mmHg | Standard Error 1.1 |
| Furosemide 60 mg + Multiple Dose Aliskiren 150mg | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 0.5 predose (msSBP) | 116.63 mmHg | Standard Error 1.8 |
| Furosemide 60 mg + Multiple Dose Aliskiren 150mg | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 12 hour Postdose (msdBP) | 68.50 mmHg | Standard Error 1.1 |
| Furosemide 60 mg + Multiple Dose Aliskiren 150mg | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 0.5 hour Postdose (msSBP) | 114.31 mmHg | Standard Error 1.8 |
| Furosemide 60 mg + Multiple Dose Aliskiren 150mg | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 4 hour Postdose (msSBP) | 101.06 mmHg | Standard Error 1.8 |
| Furosemide 60 mg + Multiple Dose Aliskiren 150mg | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 0.5 hour predose (msDBP) | 71.39 mmHg | Standard Error 1.1 |
| Furosemide 60 mg + Multiple Dose Aliskiren 150mg | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 4 hour Postdose (msDBP) | 59.07 mmHg | Standard Error 1.1 |
| Furosemide 60 mg + Multiple Dose Aliskiren 150mg | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 2 hour Postdose (msSBP) | 109.63 mmHg | Standard Error 1.8 |
| Furosemide 60 mg + Multiple Dose Aliskiren 150mg | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 24 hour Postdose (msSBP) | 118.41 mmHg | Standard Error 1.8 |
| Furosemide 60 mg + Multiple Dose Aliskiren 150mg | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 8 hour Postdose (msSBP) | 109.95 mmHg | Standard Error 1.8 |
| Furosemide 60 mg + Multiple Dose Aliskiren 150mg | Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) | 1 hour Postdose (msDBP) | 68.96 mmHg | Standard Error 1.1 |
Secondary
Plasma Pharmacokinetics (PK) of Furosemide: Area Under the Plasma Concentration-time Curve (AUC)
Pharmacokinetic (PK) parameters were determined from the plasma concentration time profile of furosemide using a non-compartmental method: AUCtau: Area under the plasma concentration-time curve from time zero to the end of the dosing interval AUC (0-24): Area under the plasma concentration-time curve from time zero to 24 hours AUClast: Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration. AUClast was calculated as the sum of linear trapezoids using non-compartmental analysis. AUCinf: Area under the plasma concentration-time curve from time zero to infinity. AUCinf was calculated by adding AUClast and the value obtained from dividing the last measurable plasma concentration by λz, where λz was determined from automated linear regression of the last three time points with non-zero concentrations in the terminal phase of the log-transformed concentration-time profile
Time frame: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post dose
Population: All patients who received at least one dose of study drug and had evaluable Pharmacokinetic (PK) data with no major protocol deviation in at least one period were included in the PK analysis set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Furosemide 60 mg + Aliskiren Placebo | Plasma Pharmacokinetics (PK) of Furosemide: Area Under the Plasma Concentration-time Curve (AUC) | AUCtau | 5217 h*ng/mL | Standard Deviation 1996.7 |
| Furosemide 60 mg + Aliskiren Placebo | Plasma Pharmacokinetics (PK) of Furosemide: Area Under the Plasma Concentration-time Curve (AUC) | AUC | 5217 h*ng/mL | Standard Deviation 1996.7 |
| Furosemide 60 mg + Aliskiren Placebo | Plasma Pharmacokinetics (PK) of Furosemide: Area Under the Plasma Concentration-time Curve (AUC) | AUClast | 5154 h*ng/mL | Standard Deviation 1999.2 |
| Furosemide 60 mg + Aliskiren Placebo | Plasma Pharmacokinetics (PK) of Furosemide: Area Under the Plasma Concentration-time Curve (AUC) | AUCinf | 5420 h*ng/mL | Standard Deviation 2005.2 |
| Furosemide 60 mg+ Single Dose Aliskiren 150mg | Plasma Pharmacokinetics (PK) of Furosemide: Area Under the Plasma Concentration-time Curve (AUC) | AUC | 4255 h*ng/mL | Standard Deviation 1390.6 |
| Furosemide 60 mg+ Single Dose Aliskiren 150mg | Plasma Pharmacokinetics (PK) of Furosemide: Area Under the Plasma Concentration-time Curve (AUC) | AUClast | 4207 h*ng/mL | Standard Deviation 1387.5 |
| Furosemide 60 mg+ Single Dose Aliskiren 150mg | Plasma Pharmacokinetics (PK) of Furosemide: Area Under the Plasma Concentration-time Curve (AUC) | AUCinf | 4559 h*ng/mL | Standard Deviation 1387.4 |
| Furosemide 60 mg+ Single Dose Aliskiren 150mg | Plasma Pharmacokinetics (PK) of Furosemide: Area Under the Plasma Concentration-time Curve (AUC) | AUCtau | 4255 h*ng/mL | Standard Deviation 1390.6 |
| Furosemide 60 mg + Multiple Dose Aliskiren 150mg | Plasma Pharmacokinetics (PK) of Furosemide: Area Under the Plasma Concentration-time Curve (AUC) | AUClast | 4535 h*ng/mL | Standard Deviation 1531.6 |
| Furosemide 60 mg + Multiple Dose Aliskiren 150mg | Plasma Pharmacokinetics (PK) of Furosemide: Area Under the Plasma Concentration-time Curve (AUC) | AUC | 4638 h*ng/mL | Standard Deviation 1532.9 |
| Furosemide 60 mg + Multiple Dose Aliskiren 150mg | Plasma Pharmacokinetics (PK) of Furosemide: Area Under the Plasma Concentration-time Curve (AUC) | AUCinf | 4783 h*ng/mL | Standard Deviation 1611.7 |
| Furosemide 60 mg + Multiple Dose Aliskiren 150mg | Plasma Pharmacokinetics (PK) of Furosemide: Area Under the Plasma Concentration-time Curve (AUC) | AUCtau | 4638 h*ng/mL | Standard Deviation 1532.9 |
| Furosemide 60 mg + Multiple Dose Aliskiren 300mg | Plasma Pharmacokinetics (PK) of Furosemide: Area Under the Plasma Concentration-time Curve (AUC) | AUCinf | 4381 h*ng/mL | Standard Deviation 1578.3 |
| Furosemide 60 mg + Multiple Dose Aliskiren 300mg | Plasma Pharmacokinetics (PK) of Furosemide: Area Under the Plasma Concentration-time Curve (AUC) | AUC | 4218 h*ng/mL | Standard Deviation 1469.3 |
| Furosemide 60 mg + Multiple Dose Aliskiren 300mg | Plasma Pharmacokinetics (PK) of Furosemide: Area Under the Plasma Concentration-time Curve (AUC) | AUCtau | 4218 h*ng/mL | Standard Deviation 1469.3 |
| Furosemide 60 mg + Multiple Dose Aliskiren 300mg | Plasma Pharmacokinetics (PK) of Furosemide: Area Under the Plasma Concentration-time Curve (AUC) | AUClast | 4130 h*ng/mL | Standard Deviation 1525.4 |
Secondary
Plasma Pharmacokinetics (PK) of Furosemide: Average Steady State Plasma Concentration During Multiple Dosing (Cav,ss)
The average steady-state drug concentration in the plasma, blood, serum, or other body fluids during multiple dosing \[amount x volume-1\]. This was estimated as AUCτ/τ
Time frame: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post dose
Population: All subjects with evaluable pharmacokinetic parameter data with no exclusion flags and no major protocol deviations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Furosemide 60 mg + Aliskiren Placebo | Plasma Pharmacokinetics (PK) of Furosemide: Average Steady State Plasma Concentration During Multiple Dosing (Cav,ss) | 217.4 ng/mL | Standard Deviation 83.196 |
| Furosemide 60 mg+ Single Dose Aliskiren 150mg | Plasma Pharmacokinetics (PK) of Furosemide: Average Steady State Plasma Concentration During Multiple Dosing (Cav,ss) | 177.3 ng/mL | Standard Deviation 57.942 |
| Furosemide 60 mg + Multiple Dose Aliskiren 150mg | Plasma Pharmacokinetics (PK) of Furosemide: Average Steady State Plasma Concentration During Multiple Dosing (Cav,ss) | 193.2 ng/mL | Standard Deviation 63.872 |
| Furosemide 60 mg + Multiple Dose Aliskiren 300mg | Plasma Pharmacokinetics (PK) of Furosemide: Average Steady State Plasma Concentration During Multiple Dosing (Cav,ss) | 175.8 ng/mL | Standard Deviation 61.219 |
Secondary
Plasma Pharmacokinetics (PK) of Furosemide: Lowest Plasma Concentration Observed During a Dosing Interval at Steady State (Cmin, ss)
The minimum observed steady-state drug concentration in the plasma, blood, serum, or other body fluids at the end of the dosing interval during multiple dosing \[amount x volume-1\]
Time frame: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 24 hours post dose
Population: All patients who received at least one dose of study drug and had evaluable PK data with no major protocol deviation in at least one period were included in the PK analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Furosemide 60 mg + Aliskiren Placebo | Plasma Pharmacokinetics (PK) of Furosemide: Lowest Plasma Concentration Observed During a Dosing Interval at Steady State (Cmin, ss) | 20.42 ng/mL | Standard Deviation 25.558 |
| Furosemide 60 mg+ Single Dose Aliskiren 150mg | Plasma Pharmacokinetics (PK) of Furosemide: Lowest Plasma Concentration Observed During a Dosing Interval at Steady State (Cmin, ss) | 20.03 ng/mL | Standard Deviation 23.78 |
| Furosemide 60 mg + Multiple Dose Aliskiren 150mg | Plasma Pharmacokinetics (PK) of Furosemide: Lowest Plasma Concentration Observed During a Dosing Interval at Steady State (Cmin, ss) | 19.80 ng/mL | Standard Deviation 29.258 |
| Furosemide 60 mg + Multiple Dose Aliskiren 300mg | Plasma Pharmacokinetics (PK) of Furosemide: Lowest Plasma Concentration Observed During a Dosing Interval at Steady State (Cmin, ss) | 16.70 ng/mL | Standard Deviation 20.868 |
Secondary
Plasma Pharmacokinetics (PK) of Furosemide: Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax, ss)
Cmax,ss was directly determined from the raw plasma concentration-time data.
Time frame: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post dose
Population: All patients who received at least one dose of study drug and had evaluable pharmacokinetic (PK) data with no major protocol deviation in at least one period were included in the PK analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Furosemide 60 mg + Aliskiren Placebo | Plasma Pharmacokinetics (PK) of Furosemide: Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax, ss) | 1702 ng/mL | Standard Deviation 708.66 |
| Furosemide 60 mg+ Single Dose Aliskiren 150mg | Plasma Pharmacokinetics (PK) of Furosemide: Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax, ss) | 1326 ng/mL | Standard Deviation 518.15 |
| Furosemide 60 mg + Multiple Dose Aliskiren 150mg | Plasma Pharmacokinetics (PK) of Furosemide: Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax, ss) | 1317 ng/mL | Standard Deviation 542.73 |
| Furosemide 60 mg + Multiple Dose Aliskiren 300mg | Plasma Pharmacokinetics (PK) of Furosemide: Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax, ss) | 1180 ng/mL | Standard Deviation 404.92 |
Secondary
Plasma Pharmacokinetics (PK) of Furosemide: Time to Reach the Maximum Concentration After Drug Administration (Tmax)
Tmax was directly determined from the raw plasma concentration-time data.
Time frame: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post dose
Population: All patients who received at least one dose of study drug and had evaluable PK data with no major protocol deviation in at least one period were included in the PK analysis set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Furosemide 60 mg + Aliskiren Placebo | Plasma Pharmacokinetics (PK) of Furosemide: Time to Reach the Maximum Concentration After Drug Administration (Tmax) | 1.500 Hours |
| Furosemide 60 mg+ Single Dose Aliskiren 150mg | Plasma Pharmacokinetics (PK) of Furosemide: Time to Reach the Maximum Concentration After Drug Administration (Tmax) | 1.500 Hours |
| Furosemide 60 mg + Multiple Dose Aliskiren 150mg | Plasma Pharmacokinetics (PK) of Furosemide: Time to Reach the Maximum Concentration After Drug Administration (Tmax) | 1.500 Hours |
| Furosemide 60 mg + Multiple Dose Aliskiren 300mg | Plasma Pharmacokinetics (PK) of Furosemide: Time to Reach the Maximum Concentration After Drug Administration (Tmax) | 2.00 Hours |
Secondary
Urine Pharmacokinetics (PK) of Furosemide: Amount of Drug Excreted Into the Urine From Time Zero to 24 Hours After Administration (Ae0-24)
The area under the plasma (or serum or blood) concentration-time curve from time zero to 24 h \[mass × time × volume-1\]
Time frame: 0 to 4, 4 to 8, 8 to 12 and 12 to 24 hours post dose
Population: All patients who received at least one dose of study drug and had evaluable PK data with no major protocol deviation in at least one period were included in the PK analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Furosemide 60 mg + Aliskiren Placebo | Urine Pharmacokinetics (PK) of Furosemide: Amount of Drug Excreted Into the Urine From Time Zero to 24 Hours After Administration (Ae0-24) | 18.61 mg | Standard Deviation 5.9012 |
| Furosemide 60 mg+ Single Dose Aliskiren 150mg | Urine Pharmacokinetics (PK) of Furosemide: Amount of Drug Excreted Into the Urine From Time Zero to 24 Hours After Administration (Ae0-24) | 15.08 mg | Standard Deviation 3.9613 |
| Furosemide 60 mg + Multiple Dose Aliskiren 150mg | Urine Pharmacokinetics (PK) of Furosemide: Amount of Drug Excreted Into the Urine From Time Zero to 24 Hours After Administration (Ae0-24) | 14.98 mg | Standard Deviation 4.5264 |
| Furosemide 60 mg + Multiple Dose Aliskiren 300mg | Urine Pharmacokinetics (PK) of Furosemide: Amount of Drug Excreted Into the Urine From Time Zero to 24 Hours After Administration (Ae0-24) | 13.63 mg | Standard Deviation 4.5134 |
Secondary
Urine Pharmacokinetics (PK) of Furosemide: Renal Clearance (CLR)
The renal clearance of drug \[volume x time-1\]
Time frame: 0 to 4, 4 to 8, 8 to 12 and 12 to 24 hours post dose
Population: All patients who received at least one dose of study drug and had evaluable pharmacodynamic (PD) data with no major protocol deviation in at least one period were included in the PD analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Furosemide 60 mg + Aliskiren Placebo | Urine Pharmacokinetics (PK) of Furosemide: Renal Clearance (CLR) | 3.808 L/h | Standard Deviation 1.3567 |
| Furosemide 60 mg+ Single Dose Aliskiren 150mg | Urine Pharmacokinetics (PK) of Furosemide: Renal Clearance (CLR) | 3.841 L/h | Standard Deviation 1.4321 |
| Furosemide 60 mg + Multiple Dose Aliskiren 150mg | Urine Pharmacokinetics (PK) of Furosemide: Renal Clearance (CLR) | 3.519 L/h | Standard Deviation 1.3592 |
| Furosemide 60 mg + Multiple Dose Aliskiren 300mg | Urine Pharmacokinetics (PK) of Furosemide: Renal Clearance (CLR) | 3.561 L/h | Standard Deviation 1.4458 |
Secondary
Urine Sodium and Potassium Excretion Per Treatment at 12 Hours Postdose
Urine was collected 12 hours postdose in all treatment groups for sodium and potassium analysis. Each patient was required to void their bladder before drug administration and at the end 12 hours.
Time frame: 12 hours postdose
Population: All patients who received at least one dose of study drug and had evaluable pharmacodynamics (PD)data with no major protocol deviation in at least one period were included in the PD analysis set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Furosemide 60 mg + Aliskiren Placebo | Urine Sodium and Potassium Excretion Per Treatment at 12 Hours Postdose | Potassium excretion | 45.013 mmol | Standard Deviation 17.3416 |
| Furosemide 60 mg + Aliskiren Placebo | Urine Sodium and Potassium Excretion Per Treatment at 12 Hours Postdose | Sodium excretion | 151.254 mmol | Standard Deviation 57.619 |
| Furosemide 60 mg+ Single Dose Aliskiren 150mg | Urine Sodium and Potassium Excretion Per Treatment at 12 Hours Postdose | Sodium excretion | 142.476 mmol | Standard Deviation 59.1617 |
| Furosemide 60 mg+ Single Dose Aliskiren 150mg | Urine Sodium and Potassium Excretion Per Treatment at 12 Hours Postdose | Potassium excretion | 37.827 mmol | Standard Deviation 16.0087 |
| Furosemide 60 mg + Multiple Dose Aliskiren 150mg | Urine Sodium and Potassium Excretion Per Treatment at 12 Hours Postdose | Sodium excretion | 144.839 mmol | Standard Deviation 63.6708 |
| Furosemide 60 mg + Multiple Dose Aliskiren 150mg | Urine Sodium and Potassium Excretion Per Treatment at 12 Hours Postdose | Potassium excretion | 46.770 mmol | Standard Deviation 17.4395 |
| Furosemide 60 mg + Multiple Dose Aliskiren 300mg | Urine Sodium and Potassium Excretion Per Treatment at 12 Hours Postdose | Potassium excretion | 44.137 mmol | Standard Deviation 11.0631 |
| Furosemide 60 mg + Multiple Dose Aliskiren 300mg | Urine Sodium and Potassium Excretion Per Treatment at 12 Hours Postdose | Sodium excretion | 140.887 mmol | Standard Deviation 68.4341 |
Secondary
Urine Sodium and Potassium Excretion Per Treatment at 24 Hours Postdose
Urine was collected 24 hours postdose in all treatment groups for sodium and potassium analysis. Each patient was required to void their bladder before drug administration and at the end 24 hours.
Time frame: 24 hours postdose
Population: All patients who received at least one dose of study drug and had evaluable pharmacodynamics (PD)data with no major protocol deviation in at least one period were included in the PD analysis set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Furosemide 60 mg + Aliskiren Placebo | Urine Sodium and Potassium Excretion Per Treatment at 24 Hours Postdose | Sodium excretion | 185.426 mmol | Standard Deviation 69.9537 |
| Furosemide 60 mg + Aliskiren Placebo | Urine Sodium and Potassium Excretion Per Treatment at 24 Hours Postdose | Potassium excretion | 57.323 mmol | Standard Deviation 20.0607 |
| Furosemide 60 mg+ Single Dose Aliskiren 150mg | Urine Sodium and Potassium Excretion Per Treatment at 24 Hours Postdose | Potassium excretion | 53.107 mmol | Standard Deviation 21.3416 |
| Furosemide 60 mg+ Single Dose Aliskiren 150mg | Urine Sodium and Potassium Excretion Per Treatment at 24 Hours Postdose | Sodium excretion | 187.256 mmol | Standard Deviation 69.1028 |
| Furosemide 60 mg + Multiple Dose Aliskiren 150mg | Urine Sodium and Potassium Excretion Per Treatment at 24 Hours Postdose | Sodium excretion | 188.886 mmol | Standard Deviation 73.8708 |
| Furosemide 60 mg + Multiple Dose Aliskiren 150mg | Urine Sodium and Potassium Excretion Per Treatment at 24 Hours Postdose | Potassium excretion | 62.715 mmol | Standard Deviation 20.4014 |
| Furosemide 60 mg + Multiple Dose Aliskiren 300mg | Urine Sodium and Potassium Excretion Per Treatment at 24 Hours Postdose | Sodium excretion | 192.176 mmol | Standard Deviation 76.0983 |
| Furosemide 60 mg + Multiple Dose Aliskiren 300mg | Urine Sodium and Potassium Excretion Per Treatment at 24 Hours Postdose | Potassium excretion | 61.012 mmol | Standard Deviation 13.6072 |
Secondary
Urine Sodium and Potassium Excretion Per Treatment at 4 Hours Postdose
Urine was collected 4 hours postdose in all treatment groups for sodium and potassium analysis. Each patient was required to void their bladder before drug administration and at the end 4 hours.
Time frame: 4 hours postdose
Population: All patients who received at least one dose of study drug and had evaluable pharmacodynamics (PD)data with no major protocol deviation in at least one period were included in the PD analysis set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Furosemide 60 mg + Aliskiren Placebo | Urine Sodium and Potassium Excretion Per Treatment at 4 Hours Postdose | Potassium excretion | 24.555 mmol | Standard Deviation 11.9749 |
| Furosemide 60 mg + Aliskiren Placebo | Urine Sodium and Potassium Excretion Per Treatment at 4 Hours Postdose | Sodium excretion | 113.992 mmol | Standard Deviation 47.5976 |
| Furosemide 60 mg+ Single Dose Aliskiren 150mg | Urine Sodium and Potassium Excretion Per Treatment at 4 Hours Postdose | Potassium excretion | 19.403 mmol | Standard Deviation 10.5975 |
| Furosemide 60 mg+ Single Dose Aliskiren 150mg | Urine Sodium and Potassium Excretion Per Treatment at 4 Hours Postdose | Sodium excretion | 104.031 mmol | Standard Deviation 49.5036 |
| Furosemide 60 mg + Multiple Dose Aliskiren 150mg | Urine Sodium and Potassium Excretion Per Treatment at 4 Hours Postdose | Sodium excretion | 98.691 mmol | Standard Deviation 55.0495 |
| Furosemide 60 mg + Multiple Dose Aliskiren 150mg | Urine Sodium and Potassium Excretion Per Treatment at 4 Hours Postdose | Potassium excretion | 23.046 mmol | Standard Deviation 8.6829 |
| Furosemide 60 mg + Multiple Dose Aliskiren 300mg | Urine Sodium and Potassium Excretion Per Treatment at 4 Hours Postdose | Potassium excretion | 21.037 mmol | Standard Deviation 7.9355 |
| Furosemide 60 mg + Multiple Dose Aliskiren 300mg | Urine Sodium and Potassium Excretion Per Treatment at 4 Hours Postdose | Sodium excretion | 93.341 mmol | Standard Deviation 43.9419 |
Secondary
Urine Sodium and Potassium Excretion Per Treatment at 8 Hours Postdose
Urine was collected 8 hours postdose in all treatment groups for sodium and potassium analysis. Each patient was required to void their bladder before drug administration and at the end 8 hours.
Time frame: 8 hours postdose
Population: All patients who received at least one dose of study drug and had evaluable pharmacodynamics (PD)data with no major protocol deviation in at least one period were included in the PD analysis set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Furosemide 60 mg + Aliskiren Placebo | Urine Sodium and Potassium Excretion Per Treatment at 8 Hours Postdose | Sodium excretion | 129.990 mmol | Standard Deviation 49.2835 |
| Furosemide 60 mg + Aliskiren Placebo | Urine Sodium and Potassium Excretion Per Treatment at 8 Hours Postdose | Potassium excretion | 33.474 mmol | Standard Deviation 12.2417 |
| Furosemide 60 mg+ Single Dose Aliskiren 150mg | Urine Sodium and Potassium Excretion Per Treatment at 8 Hours Postdose | Potassium excretion | 28.068 mmol | Standard Deviation 12.5292 |
| Furosemide 60 mg+ Single Dose Aliskiren 150mg | Urine Sodium and Potassium Excretion Per Treatment at 8 Hours Postdose | Sodium excretion | 123.835 mmol | Standard Deviation 56.2734 |
| Furosemide 60 mg + Multiple Dose Aliskiren 150mg | Urine Sodium and Potassium Excretion Per Treatment at 8 Hours Postdose | Potassium excretion | 36.120 mmol | Standard Deviation 14.4509 |
| Furosemide 60 mg + Multiple Dose Aliskiren 150mg | Urine Sodium and Potassium Excretion Per Treatment at 8 Hours Postdose | Sodium excretion | 125.677 mmol | Standard Deviation 58.6125 |
| Furosemide 60 mg + Multiple Dose Aliskiren 300mg | Urine Sodium and Potassium Excretion Per Treatment at 8 Hours Postdose | Potassium excretion | 32.498 mmol | Standard Deviation 9.6174 |
| Furosemide 60 mg + Multiple Dose Aliskiren 300mg | Urine Sodium and Potassium Excretion Per Treatment at 8 Hours Postdose | Sodium excretion | 119.776 mmol | Standard Deviation 59.0523 |