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

NCT01125514 | Completed Phase 2 Results

• 1 other identifier: CSPP100A2255
• Study Type: interventional
• Target: 37
• Locations: 2 countries
• Sites: 2

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.

Conditions

Heart Failure

Keywords

Heart failure,; aliskiren,; furosemide,; diuretic efficacy,; interaction

Outcome Measures

Primary Outcomes (4)

• 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.

  0 to 4 hours

• 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.

  0 to 24 hours

• 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.

  0 to 4 hours

• 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.

  0 to 24 hours

Secondary Outcomes (13)

• 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

• 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

• 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

• 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

• 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

Study Arms (3)

Furosemide 60 mg

EXPERIMENTAL

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.

Drug: Furosemide 60 mg; Drug: Placebo for Aliskiren

Furosemide 60 mg + Aliskiren 150 mg

EXPERIMENTAL

Treatment Period 2 (Day 8 to day 17): Patients received 60 mg furosemide, 150 mg aliskiren and 300 mg placebo once daily.

Drug: Aliskiren 150 mg; Drug: Furosemide 60 mg; Drug: Placebo for Aliskiren

Furosemide 60 mg + Aliskiren 300 mg

EXPERIMENTAL

Treatment Period 3 (Day 18 to day 27): Patients received 60 mg furosemide, 300 mg aliskiren and 150 mg placebo of aliskiren once daily.

Drug: Furosemide 60 mg; Drug: Placebo for Aliskiren; Drug: Aliskiren 300 mg

Interventions

Aliskiren 150 mg DRUG

Aliskiren 150 mg tablet

Furosemide 60 mg + Aliskiren 150 mg

Furosemide 60 mg DRUG

Furosemide 60 mg commercially-available tablets

Furosemide 60 mg; Furosemide 60 mg + Aliskiren 150 mg; Furosemide 60 mg + Aliskiren 300 mg

Placebo for Aliskiren DRUG

Matching placebo for aliskiren 150 mg and 300 mg

Furosemide 60 mg; Furosemide 60 mg + Aliskiren 150 mg; Furosemide 60 mg + Aliskiren 300 mg

Aliskiren 300 mg DRUG

Aliskiren 300 mg tablet

Furosemide 60 mg + Aliskiren 300 mg

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (2)

Novartis Investigative Site

Berlin, Germany

Location

Novartis Investigative Site

Vilnius, Lithuania

Location

MeSH Terms

Conditions

Heart Failure

Interventions

aliskiren; Furosemide

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Sulfanilamides; Sulfonamides; Amides; Organic Chemicals; Aniline Compounds; Amines; Sulfones; Sulfur Compounds

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2010
• First Posted: May 18, 2010
• Study Start: May 1, 2010
• Primary Completion: August 1, 2011
• Study Completion: August 1, 2011
• Last Updated: September 10, 2012
• Results First Posted: September 10, 2012

Record last verified: 2012-08

Locations

LI (1); DE (1)