Phase 2
Completed N=37
A Study to Investigate the Pharmacodynamic and Pharmacokinetic Interaction Between Aliskiren and Furosemide in Patients With Heart Failure
Source: ClinicalTrials.gov NCT01125514 ↗Enrolled (actual)
37
Serious AEs
2.0%
Results posted
Sep 2012
Primary outcomePrimary: Diuretic Efficacy Index 1 for Sodium Excretion — 10.185; 12.122; 13.453; 12.858 mmol/mg
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Diuretic Efficacy Index 1 for Sodium Excretion |
10.775; 13.264; 13.364; 14.747 | — |
| PRIMARY Diuretic Efficacy Index 1 for Sodium Excretion |
10.775; 13.264; 13.364; 14.747 | — |
| PRIMARY Diuretic Efficacy Index 2 for Water Excretion |
119.439; 151.859; 154.116; 175.112 | — |
| PRIMARY Diuretic Efficacy Index 2 for Water Excretion |
119.439; 151.859; 154.116; 175.112 | — |
| SECONDARY Plasma Pharmacokinetics (PK) of Furosemide: Area Under the Plasma Concentration-time Curve (AUC) |
5217; 4255; 4638; 4218; 5217; 4255 | — |
| SECONDARY Plasma Pharmacokinetics (PK) of Furosemide: Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax, ss) |
1702; 1326; 1317; 1180 | — |
| SECONDARY Plasma Pharmacokinetics (PK) of Furosemide: Time to Reach the Maximum Concentration After Drug Administration (Tmax) |
1.500; 1.500; 1.500; 2.00 | — |
| SECONDARY Plasma Pharmacokinetics (PK) of Furosemide: Average Steady State Plasma Concentration During Multiple Dosing (Cav,ss) |
217.4; 177.3; 193.2; 175.8 | — |
| SECONDARY Plasma Pharmacokinetics (PK) of Furosemide: Lowest Plasma Concentration Observed During a Dosing Interval at Steady State (Cmin, ss) |
20.42; 20.03; 19.80; 16.70 | — |
| SECONDARY Urine Pharmacokinetics (PK) of Furosemide: Amount of Drug Excreted Into the Urine From Time Zero to 24 Hours After Administration (Ae0-24) |
18.61; 15.08; 14.98; 13.63 | — |
| SECONDARY Urine Pharmacokinetics (PK) of Furosemide: Renal Clearance (CLR) |
3.808; 3.841; 3.519; 3.561 | — |
| SECONDARY Creatinine Clearance |
104.745; 109.657; 103.841; 105.304 | — |
| SECONDARY Urine Sodium and Potassium Excretion Per Treatment at 4 Hours Postdose |
113.992; 104.031; 98.691; 93.341; 24.555; 19.403 | — |
| SECONDARY Urine Sodium and Potassium Excretion Per Treatment at 8 Hours Postdose |
129.990; 123.835; 125.677; 119.776; 33.474; 28.068 | — |
| SECONDARY Urine Sodium and Potassium Excretion Per Treatment at 12 Hours Postdose |
151.254; 142.476; 144.839; 140.887; 45.013; 37.827 | — |
| SECONDARY Urine Sodium and Potassium Excretion Per Treatment at 24 Hours Postdose |
185.426; 187.256; 188.886; 192.176; 57.323; 53.107 | — |
| SECONDARY Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) |
118.26; 117.09; 116.63; 71.70; 71.41; 71.39 | — |
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
Data sourced from ClinicalTrials.gov (NCT01125514). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.