Pharmacokinetic Profile and Pharmacodynamic Characteristics of a Furosemide High Dosage Formulation in Patients With Chronic Renal Failure Undergoing Peritoneal Dialysis

Pharmacokinetic Profile and Pharmacodynamic Characteristics of a Furosemide High Dosage Formulation (PRLasix® Special, Tablets 500 mg) in Patients With Chronic Renal Failure Undergoing Peritoneal Dialysis

Primary Objective:

• To determine the absolute bioavailability of furosemide 500 mg (Lasix® Special) oral formulation in patients with chronic renal failure undergoing peritoneal dialysis.

Secondary Objectives:

• To determine the pharmacokinetic profiles of furosemide 500 mg (Lasix® Special) oral formulation and 250 mg IV formulation
• To compare the pharmacodynamic characteristics of furosemide 500 mg (Lasix® Special) oral formulation and 250 mg IV formulation

Study Overview

• Status: Completed
• Conditions: Renal Failure
• Intervention / Treatment: Drug: FUROSEMIDE; Drug: FUROSEMIDE (HOE058)

Detailed Description

• Screening: 7 to 10 days
• Treatment period: 14 days (Period 1: 7 days; Period 2: 7 days)
• End of study: 7 days after the last dosing,
• Total duration from screening per subject: 22 to 25 days.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Montreal, Canada, H1T 2M4
    • Investigational Site Number 124002

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria :

• Male or female, 18 years old or older, with chronic renal failure undergoing peritoneal dialysis for at least 3 months.
• Women of childbearing age should have a negative pregnancy test before administration of the study drug

Exclusion criteria:

• Contra-indications to furosemide, including:

  • Hypersensitivity to furosemide or to sulphonamide-derived drugs or to any ingredient in the formulation or component of the container.
  • Glomerular filtration rate below 5 mL/min
  • Glomerular filtration rate above 20 mL/min
  • Severe liver disease
  • Patients with renal failure accompanied by hepatic coma and precoma
  • Renal failure due to poisoning with nephrotoxic or hepatotoxic substances
  • Severe hyponatremia, hypokalemia, hypovolemia, dehydration or hypotension
  • Nursing women
• Pregnancy
• Treatment with any diuretic, which cannot be discontinued with the required washout period before the first drug administration
• Existence of any surgical or medical condition, which, in the judgment of the clinical investigator, might interfere with absorption, distribution, metabolism or excretion of drugs.
• Psychiatric or cognitive disturbance or illness, or recreational drug/alcohol use that, in the opinion of the principal investigator, would affect patient safety and/or compliance.
• Treatment with the following inhibitors of secretion at the renal level: clarithromycin, erythromycin, itraconazole, cyclosporin, ketoconazole, quinidine, and verapamil, which cannot be discontinued during the course of the study.

Interfering substance:Subjects must abstain from alcohol and beverages containing stimulating xanthine derivates (e.g. coffee and tea) during the entire study period.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Furosemide PO - IV; Oral furosemide allocated at the beginning of Period 1, then cross-over to IV furosemide (a minimum 7-day diuretic free washout period required between the two periods)	Drug: FUROSEMIDE; Pharmaceutical form: Solution Route of administration: Intravenous; Other Names: Furosemide Special Injection; Drug: FUROSEMIDE (HOE058); Pharmaceutical form: Tablet Route of administration: Oral; Other Names: Lasix® Special
Experimental: Furosemide IV - PO; IV furosemide allocated at the beginning of Period 1, then cross-over to oral furosemide (a minimum 7-day diuretic free washout period required between the two periods)	Drug: FUROSEMIDE; Pharmaceutical form: Solution Route of administration: Intravenous; Other Names: Furosemide Special Injection; Drug: FUROSEMIDE (HOE058); Pharmaceutical form: Tablet Route of administration: Oral; Other Names: Lasix® Special

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Absolute bioavailability (F) of a single 500-mg oral tablet	Day 1, 4, 8, 11

Secondary Outcome Measures

Outcome Measure	Time Frame
To determine the pharmacokinetic parameters of furosemide (po and iv) measured by Cmax (maximum (peak) plasma drug concentration) after single dose administration	Day 1, 4, 8, 11
To determine the pharmacokinetic parameters of furosemide (po and iv) measured by Tmax (time to reach peak or maximum concentration) following drug administration	Day 1, 4, 8, 11
To determine the pharmacokinetic parameters of furosemide (po and iv) measured by AUCT 0-72 (area under curve from the time zero to 72h)	Day 1, 4, 8, 11
To determine pharmacodynamic characteristics of furosemide (po and iv) including the excretion against time of urinary volume, urinary excretion, urea and creatinine	0, 6, 12, 24 h

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: October 30, 2012
• First Submitted That Met QC Criteria: November 7, 2012
• First Posted (Estimate): November 12, 2012

Study Record Updates

• Last Update Posted (Estimate): February 12, 2013
• Last Update Submitted That Met QC Criteria: February 11, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Renal Insufficiency; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Sodium Potassium Chloride Symporter Inhibitors; Furosemide
• Other Study ID Numbers: FUROSL06121; U1111-1127-0839 (Other Identifier: UTN)