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

Study Overview
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Brief Summary
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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

Detailed Description
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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.

Official Title
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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

Conditions
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Renal Failure

Intervention / Treatment
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* Drug: FUROSEMIDE
* Drug: FUROSEMIDE (HOE058)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Furosemide PO - IV<br>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<br>* Pharmaceutical form: Solution Route of administration: Intravenous<br>* Other names: Furosemide Special Injection;Drug: FUROSEMIDE (HOE058)<br>* Pharmaceutical form: Tablet Route of administration: Oral<br>* Other names: Lasix® Special;|
| Experimental: Furosemide IV - PO<br>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<br>* Pharmaceutical form: Solution Route of administration: Intravenous<br>* Other names: Furosemide Special Injection;Drug: FUROSEMIDE (HOE058)<br>* Pharmaceutical form: Tablet Route of administration: Oral<br>* Other names: Lasix® Special;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 |