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A Study to Investigate the Pharmacodynamic and Pharmacokinetic Interaction Between Aliskiren and Furosemide in Patients With Heart Failure

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ClinicalTrials.gov Identifier: NCT01125514
Recruitment Status : Completed
First Posted : May 18, 2010
Results First Posted : September 10, 2012
Last Update Posted : September 10, 2012
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: Single (Participant);   Primary Purpose: Treatment
Condition Heart Failure
Interventions Drug: Aliskiren 150 mg
Drug: Furosemide 60 mg
Drug: Placebo for Aliskiren
Drug: Aliskiren 300 mg
Enrollment 37
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Furosemide (Fu) /Fu+Aliskiren(Alis)150mg/fu+Alis 300mg
Hide Arm/Group Description

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.

Period Title: Treatment Period 1 (Day 1 - Day 7)
Started 37 [1]
Completed 35
Not Completed 2
Reason Not Completed
Adverse Event             1
Administrative problems             1
[1]
Randomized and safety population
Period Title: Treatment Period 2 (Day 8 - Day 17)
Started 35
Pharmacokinetic (PK) Analysis Set 33
Pharmacodynamics (PD) Analysis Set 33
Completed 32
Not Completed 3
Reason Not Completed
Adverse Event             3
Period Title: Treatment Period2(Day9-Day27) and Day 28
Started 32
Completed 28
Not Completed 4
Reason Not Completed
Adverse Event             2
Protocol Deviation             1
Withdrawal by Subject             1
Arm/Group Title Furosemide (Fu) /Fu+Aliskiren(Alis)150mg/fu+Alis 300mg
Hide Arm/Group Description

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.

Overall Number of Baseline Participants 37
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 37 participants
59.6  (11.90)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 37 participants
Female
3
   8.1%
Male
34
  91.9%
1.Primary Outcome
Title Diuretic Efficacy Index 1 for Sodium Excretion
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Furosemide 60 mg + Aliskiren Placebo Furosemide 60 mg+ Single Dose Aliskiren 150mg Furosemide 60 mg + Multiple Dose Aliskiren 150mg Furosemide 60 mg + Multiple Dose Aliskiren 300mg
Hide Arm/Group Description:
Patient received 60 mg furosemide at steady state + placebo to aliskiren from day 1 to day 7.
Patient received 60 mg furosemide at steady state + single dose aliskiren 150mg on day 8.
Patient received 60 mg furosemide at steady state + single dose aliskiren 150mg ( day 9 - day 17).
Patient received 60 mg furosemide at steady state + single dose aliskiren 300mg ( day 18 - day 27).
Overall Number of Participants Analyzed 33 32 31 28
Mean (Standard Deviation)
Unit of Measure: mmol/mg
10.185  (4.4568) 12.122  (6.2867) 13.453  (8.3524) 12.858  (6.1040)
2.Primary Outcome
Title Diuretic Efficacy Index 1 for Sodium Excretion
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Furosemide 60 mg + Aliskiren Placebo Furosemide 60 mg+ Single Dose Aliskiren 150mg Furosemide 60 mg + Multiple Dose Aliskiren 150mg Furosemide 60 mg + Multiple Dose Aliskiren 300mg
Hide Arm/Group Description:
Patient received 60 mg furosemide at steady state + placebo to aliskiren from day 1 to day 7.
Patient received 60 mg furosemide at steady state + single dose aliskiren 150mg on day 8.
Patient received 60 mg furosemide at steady state + single dose aliskiren 150mg ( day 9 - day 17).
Patient received 60 mg furosemide at steady state + single dose aliskiren 300mg ( day 18 - day 27).
Overall Number of Participants Analyzed 31 31 30 28
Mean (Standard Deviation)
Unit of Measure: mmol/mg
10.775  (5.2486) 13.264  (6.3535) 13.364  (6.1511) 14.747  (6.3531)
3.Primary Outcome
Title Diuretic Efficacy Index 2 for Water Excretion
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Furosemide 60 mg + Aliskiren Placebo Furosemide 60 mg + Single Dose Aliskiren 150mg Furosemide 60 mg + Multiple Dose Aliskiren 150mg Furosemide 60 mg + Multiple Dose Aliskiren 300mg
Hide Arm/Group Description:
Patient received 60 mg furosemide at steady state + placebo to aliskiren from day 1 to day 7.
Patient received 60 mg furosemide at steady state + single dose aliskiren 150mg on day 8.
Patient received 60 mg furosemide at steady state + single dose aliskiren 150mg ( day 9 - day 17).
Patient received 60 mg furosemide at steady state + single dose aliskiren 300mg ( day 18 - day 27).
Overall Number of Participants Analyzed 33 32 31 28
Mean (Standard Deviation)
Unit of Measure: mL/mg
90.402  (34.7866) 109.773  (50.2433) 119.239  (63.3655) 122.157  (58.8815)
4.Primary Outcome
Title Diuretic Efficacy Index 2 for Water Excretion
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Furosemide 60 mg + Aliskiren Placebo Furosemide 60 mg + Single Dose Aliskiren 150mg Furosemide 60 mg + Multiple Dose Aliskiren 150mg Furosemide 60 mg + Multiple Dose Aliskiren 300mg
Hide Arm/Group Description:
Patient received 60 mg furosemide at steady state + placebo to aliskiren from day 1 to day 7.
Patient received 60 mg furosemide at steady state + single dose aliskiren 150mg on day 8.
Patient received 60 mg furosemide at steady state + single dose aliskiren 150mg ( day 9 - day 17).
Patient received 60 mg furosemide at steady state + single dose aliskiren 300mg ( day 18 - day 27).
Overall Number of Participants Analyzed 31 32 30 28
Mean (Standard Deviation)
Unit of Measure: mL/mg
119.439  (46.2607) 151.859  (53.6734) 154.116  (40.5598) 175.112  (59.4236)
5.Secondary Outcome
Title Plasma Pharmacokinetics (PK) of Furosemide: Area Under the Plasma Concentration-time Curve (AUC)
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Furosemide 60 mg + Aliskiren Placebo Furosemide 60 mg + Single Dose Aliskiren 150mg Furosemide 60 mg + Multiple Dose Aliskiren 150mg Furosemide 60 mg + Multiple Dose Aliskiren 300mg
Hide Arm/Group Description:
Patient received 60 mg furosemide at steady state + placebo to aliskiren from day 1 to day 7.
Patient received 60 mg furosemide at steady state + single dose aliskiren 150mg on day 8.
Patient received 60 mg furosemide at steady state + single dose aliskiren 150mg ( day 9 - day 17).
Patient received 60 mg furosemide at steady state + single dose aliskiren 300mg ( day 18 - day 27).
Overall Number of Participants Analyzed 33 31 31 28
Mean (Standard Deviation)
Unit of Measure: h*ng/mL
AUCtau 5217  (1996.7) 4255  (1390.6) 4638  (1532.9) 4218  (1469.3)
AUC 5217  (1996.7) 4255  (1390.6) 4638  (1532.9) 4218  (1469.3)
AUClast 5154  (1999.2) 4207  (1387.5) 4535  (1531.6) 4130  (1525.4)
AUCinf 5420  (2005.2) 4559  (1387.4) 4783  (1611.7) 4381  (1578.3)
6.Secondary Outcome
Title Plasma Pharmacokinetics (PK) of Furosemide: Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax, ss)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Furosemide 60 mg + Aliskiren Placebo Furosemide 60 mg + Single Dose Aliskiren 150mg Furosemide 60 mg + Multiple Dose Aliskiren 150mg Furosemide 60 mg + Multiple Dose Aliskiren 300mg
Hide Arm/Group Description:
Patient received 60 mg furosemide at steady state + placebo to aliskiren from day 1 to day 7.
Patient received 60 mg furosemide at steady state + single dose aliskiren 150mg on day 8.
Patient received 60 mg furosemide at steady state + single dose aliskiren 150mg ( day 9 - day 17).
Patient received 60 mg furosemide at steady state + single dose aliskiren 300mg ( day 18 - day 27).
Overall Number of Participants Analyzed 33 31 31 28
Mean (Standard Deviation)
Unit of Measure: ng/mL
1702  (708.66) 1326  (518.15) 1317  (542.73) 1180  (404.92)
7.Secondary Outcome
Title Plasma Pharmacokinetics (PK) of Furosemide: Time to Reach the Maximum Concentration After Drug Administration (Tmax)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Furosemide 60 mg + Aliskiren Placebo Furosemide 60 mg + Single Dose Aliskiren 150mg Furosemide 60 mg + Multiple Dose Aliskiren 150mg Furosemide 60 mg + Multiple Dose Aliskiren 300mg
Hide Arm/Group Description:
Patient received 60 mg furosemide at steady state + placebo to aliskiren from day 1 to day 7.
Patient received 60 mg furosemide at steady state + single dose aliskiren 150mg on day 8.
Patient received 60 mg furosemide at steady state + single dose aliskiren 150mg ( day 9 - day 17).
Patient received 60 mg furosemide at steady state + single dose aliskiren 300mg ( day 18 - day 27).
Overall Number of Participants Analyzed 33 31 31 28
Median (Full Range)
Unit of Measure: Hours
1.500
(1.00 to 3.00)
1.500
(0.500 to 3.00)
1.500
(1.00 to 4.00)
2.00
(0.500 to 3.00)
8.Secondary Outcome
Title Plasma Pharmacokinetics (PK) of Furosemide: Average Steady State Plasma Concentration During Multiple Dosing (Cav,ss)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects with evaluable pharmacokinetic parameter data with no exclusion flags and no major protocol deviations.
Arm/Group Title Furosemide 60 mg + Aliskiren Placebo Furosemide 60 mg + Single Dose Aliskiren 150mg Furosemide 60 mg + Multiple Dose Aliskiren 150mg Furosemide 60 mg + Multiple Dose Aliskiren 300mg
Hide Arm/Group Description:
Patient received 60 mg furosemide at steady state + placebo to aliskiren from day 1 to day 7.
Patient received 60 mg furosemide at steady state + single dose aliskiren 150mg on day 8.
Patient received 60 mg furosemide at steady state + single dose aliskiren 150mg ( day 9 - day 17).
Patient received 60 mg furosemide at steady state + single dose aliskiren 300mg ( day 18 - day 27).
Overall Number of Participants Analyzed 33 31 31 28
Mean (Standard Deviation)
Unit of Measure: ng/mL
217.4  (83.196) 177.3  (57.942) 193.2  (63.872) 175.8  (61.219)
9.Secondary Outcome
Title Plasma Pharmacokinetics (PK) of Furosemide: Lowest Plasma Concentration Observed During a Dosing Interval at Steady State (Cmin, ss)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Furosemide 60 mg + Aliskiren Placebo Furosemide 60 mg + Single Dose Aliskiren 150mg Furosemide 60 mg+ Multiple Dose Aliskiren 150mg Furosemide 60 mg + Multiple Dose Aliskiren 300mg
Hide Arm/Group Description:
Patient received 60 mg furosemide at steady state + placebo to aliskiren from day 1 to day 7.
Patient received 60 mg furosemide at steady state + single dose aliskiren 150mg on day 8.
Patient received 60 mg furosemide at steady state + single dose aliskiren 150mg ( day 9 - day 17).
Patient received 60 mg furosemide at steady state + single dose aliskiren 300mg ( day 18 - day 27).
Overall Number of Participants Analyzed 33 31 31 28
Mean (Standard Deviation)
Unit of Measure: ng/mL
20.42  (25.558) 20.03  (23.780) 19.80  (29.258) 16.70  (20.868)
10.Secondary Outcome
Title Urine Pharmacokinetics (PK) of Furosemide: Amount of Drug Excreted Into the Urine From Time Zero to 24 Hours After Administration (Ae0-24)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Furosemide 60 mg + Aliskiren Placebo Furosemide 60 mg + Single Dose Aliskiren 150mg Furosemide 60 mg + Multiple Dose Aliskiren 150mg Furosemide 60 mg+ Multiple Dose Aliskiren 300mg
Hide Arm/Group Description:
Patient received 60 mg furosemide at steady state + placebo to aliskiren from day 1 to day 7.
Patient received 60 mg furosemide at steady state + single dose aliskiren 150mg on day 8.
Patient received 60 mg furosemide at steady state + single dose aliskiren 150mg ( day 9 - day 17).
Patient received 60 mg furosemide at steady state + single dose aliskiren 300mg ( day 18 - day 27).
Overall Number of Participants Analyzed 31 31 30 28
Mean (Standard Deviation)
Unit of Measure: mg
18.61  (5.9012) 15.08  (3.9613) 14.98  (4.5264) 13.63  (4.5134)
11.Secondary Outcome
Title Urine Pharmacokinetics (PK) of Furosemide: Renal Clearance (CLR)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Furosemide 60 mg + Aliskiren Placebo Furosemide 60 mg + Single Dose Aliskiren 150mg Furosemide 60 mg + Multiple Dose Aliskiren 150mg Furosemide 60 mg + Multiple Dose Aliskiren 300mg
Hide Arm/Group Description:
Patient received 60 mg furosemide at steady state + placebo to aliskiren from day 1 to day 7.
Patient received 60 mg furosemide at steady state + single dose aliskiren 150mg on day 8.
Patient received 60 mg furosemide at steady state + single dose aliskiren 150mg ( day 9 - day 17).
Patient received 60 mg furosemide at steady state + single dose aliskiren 300mg ( day 18 - day 27).
Overall Number of Participants Analyzed 31 31 30 28
Mean (Standard Deviation)
Unit of Measure: L/h
3.808  (1.3567) 3.841  (1.4321) 3.519  (1.3592) 3.561  (1.4458)
12.Secondary Outcome
Title Creatinine Clearance
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Furosemide 60 mg + Aliskiren Placebo Furosemide 60 mg + Single Dose Aliskiren 150mg Furosemide 60 mg + Multiple Dose Aliskiren 150mg Furosemide 60 mg + Multiple Dose Aliskiren 300mg
Hide Arm/Group Description:
Patient received 60 mg furosemide at steady state + placebo to aliskiren from day 1 to day 7.
Patient received 60 mg furosemide at steady state + single dose aliskiren 150mg on day 8.
Patient received 60 mg furosemide at steady state + single dose aliskiren 150mg ( day 9 - day 17).
Patient received 60 mg furosemide at steady state + single dose aliskiren 300mg ( day 18 - day 27).
Overall Number of Participants Analyzed 32 32 29 28
Mean (Standard Deviation)
Unit of Measure: mL/min
104.745  (38.2884) 109.657  (30.0667) 103.841  (28.2845) 105.304  (25.4076)
13.Secondary Outcome
Title Urine Sodium and Potassium Excretion Per Treatment at 4 Hours Postdose
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Furosemide 60 mg + Aliskiren Placebo Furosemide 60 mg + Single Dose Aliskiren 150mg Furosemide 60 mg + Multiple Dose Aliskiren 150mg Furosemide 60 mg + Multiple Dose Aliskiren 300mg
Hide Arm/Group Description:
Patient received 60 mg furosemide at steady state + placebo to aliskiren from day 1 to day 7.
Patient received 60 mg furosemide at steady state + single dose aliskiren 150mg on day 8.
Patient received 60 mg furosemide at steady state + single dose aliskiren 150mg ( day 9 - day 17).
Patient received 60 mg furosemide at steady state + single dose aliskiren 300mg ( day 18 - day 27).
Overall Number of Participants Analyzed 33 32 31 28
Mean (Standard Deviation)
Unit of Measure: mmol
Sodium excretion 113.992  (47.5976) 104.031  (49.5036) 98.691  (55.0495) 93.341  (43.9419)
Potassium excretion 24.555  (11.9749) 19.403  (10.5975) 23.046  (8.6829) 21.037  (7.9355)
14.Secondary Outcome
Title Urine Sodium and Potassium Excretion Per Treatment at 8 Hours Postdose
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Furosemide 60 mg + Aliskiren Placebo Furosemide 60 mg + Single Dose Aliskiren 150mg Furosemide 60 mg + Multiple Dose Aliskiren 150mg Furosemide 60 mg + Multiple Dose Aliskiren 300mg
Hide Arm/Group Description:
Patient received 60 mg furosemide at steady state + placebo to aliskiren from day 1 to day 7.
Patient received 60 mg furosemide at steady state + single dose aliskiren 150mg on day 8.
Patient received 60 mg furosemide at steady state + single dose aliskiren 150mg ( day 9 - day 17).
Patient received 60 mg furosemide at steady state + single dose aliskiren 300mg ( day 18 - day 27).
Overall Number of Participants Analyzed 33 31 31 28
Mean (Standard Deviation)
Unit of Measure: mmol
Sodium excretion 129.990  (49.2835) 123.835  (56.2734) 125.677  (58.6125) 119.776  (59.0523)
Potassium excretion 33.474  (12.2417) 28.068  (12.5292) 36.120  (14.4509) 32.498  (9.6174)
15.Secondary Outcome
Title Urine Sodium and Potassium Excretion Per Treatment at 12 Hours Postdose
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Furosemide 60 mg + Aliskiren Placebo Furosemide 60 mg + Single Dose Aliskiren 150mg Furosemide 60 mg + Multiple Dose Aliskiren 150mg Furosemide 60 mg + Multiple Dose Aliskiren 300mg
Hide Arm/Group Description:
Patient received 60 mg furosemide at steady state + placebo to aliskiren from day 1 to day 7.
Patient received 60 mg furosemide at steady state + single dose aliskiren 150mg on day 8.
Patient received 60 mg furosemide at steady state + single dose aliskiren 150mg ( day 9 - day 17).
Patient received 60 mg furosemide at steady state + single dose aliskiren 300mg ( day 18 - day 27).
Overall Number of Participants Analyzed 32 32 31 27
Mean (Standard Deviation)
Unit of Measure: mmol
Sodium excretion 151.254  (57.6190) 142.476  (59.1617) 144.839  (63.6708) 140.887  (68.4341)
Potassium excretion 45.013  (17.3416) 37.827  (16.0087) 46.770  (17.4395) 44.137  (11.0631)
16.Secondary Outcome
Title Urine Sodium and Potassium Excretion Per Treatment at 24 Hours Postdose
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Furosemide 60 mg + Aliskiren Placebo Furosemide 60 mg + Single Dose Aliskiren 150mg Furosemide 60 mg + Multiple Dose Aliskiren 150mg Furosemide 60 mg + Multiple Dose Aliskiren 300mg
Hide Arm/Group Description:
Patient received 60 mg furosemide at steady state + placebo to aliskiren from day 1 to day 7.
Patient received 60 mg furosemide at steady state + single dose aliskiren 150mg on day 8.
Patient received 60 mg furosemide at steady state + single dose aliskiren 150mg ( day 9 - day 17).
Patient received 60 mg furosemide at steady state + single dose aliskiren 300mg ( day 18 - day 27).
Overall Number of Participants Analyzed 31 31 30 28
Mean (Standard Deviation)
Unit of Measure: mmol
Sodium excretion 185.426  (69.9537) 187.256  (69.1028) 188.886  (73.8708) 192.176  (76.0983)
Potassium excretion 57.323  (20.0607) 53.107  (21.3416) 62.715  (20.4014) 61.012  (13.6072)
17.Secondary Outcome
Title Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP)
Hide Description 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set include subjects that received study drug.
Arm/Group Title Furosemide 60 mg + Aliskiren Placebo Furosemide 60 mg + Multiple Dose Aliskiren 150mg Furosemide go mg + Multiple Dose Aliskiren 300mg
Hide Arm/Group Description:
Patient received 60 mg furosemide at steady state + placebo to aliskiren from day 1 to day 7.
Patient received 60 mg furosemide at steady state + single dose aliskiren 150mg ( day 9 - day 17).
Patient received 60 mg furosemide at steady state + single dose aliskiren 300mg ( day 18 - day 27).
Overall Number of Participants Analyzed 37 35 32
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
0.5 predose (msSBP) 118.26  (1.62) 117.09  (1.70) 116.63  (1.80)
0.5 hour predose (msDBP) 71.70  (0.98) 71.41  (1.04) 71.39  (1.10)
0.5 hour Postdose (msSBP) 114.78  (1.64) 113.19  (1.70) 114.31  (1.80)
0.5 hour Postdose (msDBP) 70.94  (1.00) 69.04  (1.04) 69.86  (1.10)
1 hour Postdose (msSBP) 115.15  (1.64) 112.22  (1.70) 112.16  (1.80)
1 hour Postdose (msDBP) 71.22  (1.00) 69.04  (1.04) 68.96  (1.10)
2 hour Postdose (msSBP) 113.61  (1.64) 109.22  (1.70) 109.63  (1.80)
2 hour Postdose (msDBP) 68.39  (1.10) 67.50  (1.04) 68.39  (1.10)
4 hour Postdose (msSBP) 106.50  (1.64) 101.84  (1.70) 101.06  (1.80)
4 hour Postdose (msDBP) 63.85  (1.00) 62.32  (1.04) 59.07  (1.10)
8 hour Postdose (msSBP) 110.75  (1.66) 112.09  (1.70) 109.95  (1.80)
8 hour Postdose (msDBP) 66.33  (1.01) 66.94  (1.04) 66.46  (1.10)
12 hour Postdose (msSBP) 116.99  (1.66) 116.90  (1.70) 115.16  (1.80)
12 hour Postdose (msdBP) 67.86  (1.01) 68.79  (1.04) 68.50  (1.10)
24 hour Postdose (msSBP) 115.49  (1.66) 116.69  (1.72) 118.41  (1.80)
24 hour Postdose (msDBP) 71.24  (1.01) 71.66  (1.05) 72.32  (1.10)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title 60 mg Furosemide + 150 mg Placebo + 300 mg Placebo 60 mg Furosemide + 150 mg Aliskiren + 300 mg Placebo 60 mg Furosemide + 300 mg Aliskiren + 150 mg Placebo
Hide Arm/Group Description 60 mg furosemide + 150 mg placebo + 300 mg placebo 60 mg furosemide + 150 mg aliskiren + 300 mg placebo 60 mg furosemide + 300 mg aliskiren + 150 mg placebo
All-Cause Mortality
60 mg Furosemide + 150 mg Placebo + 300 mg Placebo 60 mg Furosemide + 150 mg Aliskiren + 300 mg Placebo 60 mg Furosemide + 300 mg Aliskiren + 150 mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
60 mg Furosemide + 150 mg Placebo + 300 mg Placebo 60 mg Furosemide + 150 mg Aliskiren + 300 mg Placebo 60 mg Furosemide + 300 mg Aliskiren + 150 mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/37 (5.41%)   0/33 (0.00%)   0/31 (0.00%) 
Injury, poisoning and procedural complications       
Rib fracture  1  1/37 (2.70%)  0/33 (0.00%)  0/31 (0.00%) 
Metabolism and nutrition disorders       
Gout  1  1/37 (2.70%)  0/33 (0.00%)  0/31 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Haemothorax  1  1/37 (2.70%)  0/33 (0.00%)  0/31 (0.00%) 
Pneumothorax  1  1/37 (2.70%)  0/33 (0.00%)  0/31 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
60 mg Furosemide + 150 mg Placebo + 300 mg Placebo 60 mg Furosemide + 150 mg Aliskiren + 300 mg Placebo 60 mg Furosemide + 300 mg Aliskiren + 150 mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/37 (0.00%)   0/33 (0.00%)   0/31 (0.00%) 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
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Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01125514     History of Changes
Other Study ID Numbers: CSPP100A2255
First Submitted: May 17, 2010
First Posted: May 18, 2010
Results First Submitted: August 9, 2012
Results First Posted: September 10, 2012
Last Update Posted: September 10, 2012