Pharmacokinetic, Pharmacodynamic and Tolerability Study of Otamixaban in Patients With Mild, Moderate and Severe Renal Impairment

Study Overview
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Brief Summary
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Primary Objective: To study effect of mild, moderate and severe renal impairment on the pharmacokinetics of Otamixaban. Secondary Objective: To assess the pharmacodynamic effects of Otamixaban on subjects with mild, moderate and severe renal impairment and in matched subjects with normal renal function.

Detailed Description
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The study period for one subject is broken down as follows: 2 to 28 days of screening, 1 day of treatment, 8 to 11 days of follow-up after start of infusion. There are 5 days in the unit starting the day before the start of infusion.

Official Title
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An Open-label Pharmacokinetic, Pharmacodynamic and Tolerability Study of Otamixaban Given as a Single 80 μg/kg Bolus Plus 100 µg/kg/h Continuous Infusion for 24 Hours in Subjects With Mild, Moderate and Severe Renal Impairment, and in Matched Subjects With Normal Renal Function

Conditions
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Renal Impairment

Intervention / Treatment
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* Drug: OTAMIXABAN (XRP0673)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Subject with renal impairment: Mild, moderate or severe renal impairment defined as Creatinine Clearance (CrCl) from 50 to 80, 30 to 50 and < 30 mL/min respectively, based on the Cockcroft-Gault formula, Body weight between 50.0 kg and 115.0 kg inclusive if male, between 40.0 kg and 95.0 kg inclusive if female, Body Mass Index between 18.0 and 34.9 kg/m2 inclusive. Stable chronic renal impairment as defined by Cockcroft-Gault formula, Vital signs, cardiac function and laboratory parameters within the acceptable range. Or matched subject (by age, gender and body weight) with normal renal function (defined as CrCl >80 mL/min) and certified as healthy by physical examination, medical history and laboratory findings. If female, subject must use a double contraception method, except if she is sterilized for more than 3 months or postmenopausal. Exclusion criteria: Uncontrolled clinically relevant cardiovascular, pulmonary, gastro-intestinal, metabolic, hematological, neurological, psychiatric, systemic, ocular, gynecologic (if female) or infectious disease, or signs of acute illness. Active hepatitis, hepatic insufficiency. Acute renal failure, nephrotic syndrome. History of or current hematuria of urologic origin. Subject requiring dialysis during the study. History or presence of drug or alcohol abuse within two years before inclusion. Smoking more than 15 cigarettes or equivalent per day. Any significant change in chronic treatment medication within 14-days before inclusion. 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
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Severe renal impairment population<br> | Drug: OTAMIXABAN (XRP0673)<br>* Form: solution for injection Route: intravenous<br>|
| Experimental: Moderate renal impairment population<br> | Drug: OTAMIXABAN (XRP0673)<br>* Form: solution for injection Route: intravenous<br>|
| Experimental: Mild renal impairment population<br> | Drug: OTAMIXABAN (XRP0673)<br>* Form: solution for injection Route: intravenous<br>|
| Experimental: Healthy population<br>Healthy matched subjects | Drug: OTAMIXABAN (XRP0673)<br>* Form: solution for injection Route: intravenous<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of Otamixaban (Observed concentration at the end of the infusion (Ceoi) and Areas Under the plasma concentration Curve(AUClast and AUC)) |  | 4 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacodynamic effect based on coagulation parameters (activated Partial Prothrombin Time (aPTT), Prothrombin Time (PT) and International Normalized Ratio (INR)) |  | 4 days |