Study to Assess Bemiparin Pharmacokinetics in Renal Insufficiency and in the Elderly

Clinical Trial to Assess Bemiparin Pharmacokinetics at Therapeutic (115 IU/kg) and Prophylactic Doses (3500 IU) Administered Subcutaneously in Single or Multiple Doses in Renal Insufficiency and in the Elderly

Open pharmacokinetic study with 5 parallel groups and two treatment phases (bemiparin 3,500 IU multiple dose and bemiparin 115 IU/kg single dose). The bemiparin pharmacokinetic profile will be assessed by measuring its effects on the coagulation cascade. Plasma anti-Xa activity (measured using chromogenic amidolytic assay) in IU per milliliter will be the primary endpoint to assess the pharmacokinetic profile of bemiparin.

Study Overview

• Status: Completed
• Conditions: Renal Insufficiency
• Intervention / Treatment: Drug: bemiparin

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08008
    • Hospital de la Santa Creu i Sant Pau and Fundació Puigvert

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:

Non-elderly healthy volunteers (Group I):

• Male or female subjects aged between 18 and 65 years
• body weight, clinical history, physical examination, vital signs (systolic and diastolic blood pressure, heart beat rate and body temperature), ECG and laboratory tests (hemogram and biochemistry) within normal range
• without evidence of significant organic or psychiatric illness
• who have accepted to participate in the study and have signed the written informed consent.

Patients with renal insufficiency (Groups II, III and IV):

• Male or female subjects aged between 18 and 65 years, who will be assigned to one of the following groups according to renal function:

  • Group II: mild renal insufficiency (creatinine clearance > 50 to 80 ml/min);
  • Group III: Moderate renal insufficiency (creatinine clearance: 30 to 50 ml/min);
  • Group IV: Severe renal insufficiency (creatinine clearance < 30 ml/min). The degree of renal insufficiency will be calculated on the basis of determination of creatinine clearance measuring total urinary output over a 24-h period and serum creatinine levels. Urine samples will be collected no more than 2 weeks before the first experimental period.
• Patients with renal insufficiency must have a stable renal function during the 3 months before their inclusion in the study.
• They must have a body weight between 45 and 110 Kg.
• They have to accept to participate in the study and have signed the written informed consent.

Elderly healthy volunteers (Group V):

• Male or female subjects aged > 65 years old who fulfill with the remaining inclusion criteria specified for non-elderly healthy volunteers.

Exclusion Criteria:

Non-elderly healthy volunteers (Group I):

• Previous history of alcoholism or drugs consumption
• Important consumer of exciting drinks
• Hypersensitivity, allergy, idiosyncrasy to medicines
• Taking another medication four weeks before the initiation of the trial including medication without prescription and medicinal plants
• Positive serology of hepatitis B, C or HIV virus
• History or clinic evidence of concomitant disease
• Familiar history of coagulation's disorders
• surgery within the previous 6 months
• Women who are pregnant or who are not using effective contra conceptive methods
• Ethanol, cannabis, cocaine, amphetamine, benzodiazepin or opiate in urine
• Current platelet count < 100.000/mm3 or serum K > 5,5 mEq/L
• Any contraindication to bemiparin administration in order to authorized summary product characteristics
• Healthy volunteers who are not participating in another clinical trial or have not done so in the past 2 months
• To give blood in the four weeks before beginning of the trial

Patients with renal insufficiency or elderly healthy volunteers (Groups II, III, IV, V):

• Previous history of alcoholism or drugs consumption
• Important consumer of exciting drinks
• Hypersensitivity, allergy, idiosyncrasy to medicines
• Treatment with enzymatic inhibitors or inductors medicines
• Administration with ASA of dosis > 125 mg/day and/or NDAIs with half-life > 20 hours or with high antiagregant effect during the previous ten days to the inclusion
• Chronic hepatopatology
• bilirubin levels > 1,5 mg/dl and/or increment of AST/ALT levels twice higher than maximum limit of normality
• prothrombin time 20% higher than maximun limit of normality and haemoglobine < 8gr/dl or albumim levels <3gr/dl
• Previous history of acute infarction of myocardium, cardiac ischemic or arrhythmia
• Acute illness in the previous week to the participation
• Familiar history of coagulation's disorders
• surgery within the previous 6 months
• Women who are pregnant or who are not using effective contra conceptive methods
• Ethanol, cannabis, cocaine, amphetamine, benzodiazepin or opiate in urine
• Current platelet count < 75.000/mm3 or serum K > 6 mEq/L
• Any contraindication to bemiparin administration in order to authorized summary product characteristics
• Healthy volunteers who are not participating in another clinical trial or have not done so in the past 2 months
• To give blood in the four weeks before beginning of the trial
• Subjects in haemodialysis or peritoneal dialysis

Study Plan

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
To assess the pharmacokinetics of bemiparin administered subcutaneously once daily for 4 days at prophylactic doses (3500 IU) and at a single therapeutic dose (115 IU/kg), in renal insufficiency and in the elderly.

Secondary Outcome Measures

Outcome Measure
To assess the safety and tolerability of bemiparin in all volunteers and patients.

Collaborators and Investigators

• Sponsor: Rovi Pharmaceuticals Laboratories
• Investigators: Principal Investigator: Manuel Barbanoj, MD, Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

Study record dates

Study Major Dates

• Study Start: March 1, 2006
• Primary Completion (Actual): February 1, 2011
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: December 14, 2006
• First Submitted That Met QC Criteria: December 18, 2006
• First Posted (Estimate): December 19, 2006

Study Record Updates

• Last Update Posted (Estimate): March 18, 2011
• Last Update Submitted That Met QC Criteria: March 17, 2011
• Last Verified: March 1, 2011

More Information

Terms related to this study

• Keywords: elderly; pharmacokinetics; low molecular weight heparin; renal insufficency
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Anticoagulants; Bemiparin
• Other Study ID Numbers: ROV-BEM-2005-01