Clinical trial NCT01125514: A Study to Investigate the Pharmacodynamic and Pharmacokinetic Interaction Between Aliskiren and Furosemide in Patients With Heart Failure
Official title: A Single-blind, Multiple Dose, Placebo-controlled, Double Dummy Study to Investigate the Pharmacodynamic and Pharmacokinetic Interaction Between Aliskiren and Furosemide in Patients With Heart Failure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Heart Failure
Keywords: Heart failure,
aliskiren,
furosemide,
diuretic efficacy,
interaction
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2010-05-18
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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/exclusion criteria may apply

Primary outcomes:
measure: Diuretic Efficacy Index 1 for Sodium Excretion
timeFrame: 0 to 4 hours
measure: Diuretic Efficacy Index 1 for Sodium Excretion
timeFrame: 0 to 24 hours
measure: Diuretic Efficacy Index 2 for Water Excretion
timeFrame: 0 to 4 hours
measure: Diuretic Efficacy Index 2 for Water Excretion
timeFrame: 0 to 24 hours
Secondary outcomes:
measure: Plasma Pharmacokinetics (PK) of Furosemide: Area Under the Plasma Concentration-time Curve (AUC)
timeFrame: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post dose
measure: Plasma Pharmacokinetics (PK) of Furosemide: Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax, ss)
timeFrame: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post dose
measure: Plasma Pharmacokinetics (PK) of Furosemide: Time to Reach the Maximum Concentration After Drug Administration (Tmax)
timeFrame: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post dose
measure: Plasma Pharmacokinetics (PK) of Furosemide: Average Steady State Plasma Concentration During Multiple Dosing (Cav,ss)
timeFrame: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post dose
measure: Plasma Pharmacokinetics (PK) of Furosemide: Lowest Plasma Concentration Observed During a Dosing Interval at Steady State (Cmin, ss)
timeFrame: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 24 hours post dose
measure: Urine Pharmacokinetics (PK) of Furosemide: Amount of Drug Excreted Into the Urine From Time Zero to 24 Hours After Administration (Ae0-24)
timeFrame: 0 to 4, 4 to 8, 8 to 12 and 12 to 24 hours post dose
measure: Urine Pharmacokinetics (PK) of Furosemide: Renal Clearance (CLR)
timeFrame: 0 to 4, 4 to 8, 8 to 12 and 12 to 24 hours post dose
measure: Creatinine Clearance
timeFrame: 0 to 4, 4 to 8, 8 to 12 and 12 to 24 hours post dose
measure: Urine Sodium and Potassium Excretion Per Treatment at 4 Hours Postdose
timeFrame: 4 hours postdose
measure: Urine Sodium and Potassium Excretion Per Treatment at 8 Hours Postdose
timeFrame: 8 hours postdose
measure: Urine Sodium and Potassium Excretion Per Treatment at 12 Hours Postdose
timeFrame: 12 hours postdose
measure: Urine Sodium and Potassium Excretion Per Treatment at 24 Hours Postdose
timeFrame: 24 hours postdose
measure: Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP)
timeFrame: 0.5 hour pre-dose, 0.5, 1, 2, 4, 8, 12 and 24 hours post dose.
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Vilnius
country: Lithuania
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: