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

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

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.

Study Overview

• Status: Completed
• Conditions: Renal Impairment
• Intervention / Treatment: Drug: OTAMIXABAN (XRP0673)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami Gardens, Florida, United States, 33169
      • Investigational Site Number 840003
    • Orlando, Florida, United States, 32806
      • Investigational Site Number 840005
  • Minnesota
    • St. Paul, Minnesota, United States, 55144
      • Investigational Site Number 840004
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Investigational Site Number 840002

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: May 6, 2010
• First Submitted That Met QC Criteria: May 7, 2010
• First Posted (Estimate): May 10, 2010

Study Record Updates

• Last Update Posted (Estimate): May 12, 2014
• Last Update Submitted That Met QC Criteria: May 9, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Otamixaban
• Other Study ID Numbers: POP6537; U1111-1116-5821 (Other Identifier: UTN)