Pharmacokinetic, Pharmacodynamic and Tolerability Study of Otamixaban in Patients With Mild and Moderate Hepatic 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 and Moderate Hepatic Impairment, and in Matched Subjects With Normal Hepatic Function.

Primary Objective:

- To study effect of mild and moderate hepatic impairment on the pharmacokinetics of otamixaban.

Secondary Objective:

- To assess the pharmacodynamic effects of otamixaban on subjects with mild and moderate hepatic impairment and in matched subjects with normal hepatic function.

Study Overview

• Status: Completed
• Conditions: Hepatic Impairment
• Intervention / Treatment: Drug: otamixaban XRP0673

Detailed Description

The duration of each part of the study for one subject was 28 days of screening, 1 day of treatment, with 5 days in the unit (Day -1 to Day 4) and a 8 to 11 days of follow-up after start of infusion.

• Study Type: Interventional
• Enrollment (Actual): 25
• 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, 32809
      • Investigational Site Number 840001
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Investigational Site Number 840002

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

- Subjects with hepatic impairment:

• Body weight between 50.0 kg and 115.0 kg inclusive if male, between 40.0 kg and 100.0 kg inclusive if female, Body Mass Index between 18.0 and 34.9 kg/m2 inclusive
• Stable chronic liver disease assessed by medical history, physical examination, laboratory values
• Vital signs, cardiac function and laboratory parameters within the acceptable range for subjects with hepatic impairment
• If female, subject must use a double contraception method, except if she is sterilized for more than 3 months or postmenopausal
• Patients with hepatic impairment will be matched to healthy subjects who are defined as healthy by physical examination, medical history and laboratory findings and are matched to patients with respect to age, gender, and body weight. Inclusion/exclusion criteria for healthy subjects may differ slightly from those listed for patients and are defined in the study protocol

Exclusion criteria:

• Uncontrolled clinically relevant cardiovascular, pulmonary, gastrointestinal, metabolic, hematological, neurological, psychiatric, systemic, ocular, gynecologic (if female), or infectious disease, or signs of acute illness
• Creatinine level above the upper limit of normal
• Hepatocarcinoma
• Acute hepatitis
• Hepatic encephalopathy grade 2, 3 and 4
• History or presence of drug or alcohol abuse within two years before inclusion
• Smoking more than 15 cigarettes or equivalent per day, unable to refrain from smoking during the institutionalization
• 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: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mild impairment; Patients with mild hepatic impairment	Drug: otamixaban XRP0673; Pharmaceutical form: solution for injection Route of administration: intravenous
Experimental: Moderate impairment; Patients with moderate impairment	Drug: otamixaban XRP0673; Pharmaceutical form: solution for injection Route of administration: intravenous
Experimental: Healthy subjects; Matched healthy subjects	Drug: otamixaban XRP0673; Pharmaceutical form: solution for injection Route of administration: intravenous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
PK parameters including Ceoi, AUClast, AUC, C1min, CL, Vss, and t1/2z	Day 1 to Day 4
Pharmacodynamic based on coagulation parameters, activated partial prothrombin time (aPTT), prothrombin time (PT), and international normalized ratio (INR)	Screening (-28 days) up to 4 days after treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety based on treatment-emergent adverse events, clinical laboratory evaluations, vital signs, and ECG	Screening (-28 days) up 8 to 11 days after treament

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: May 17, 2010
• First Submitted That Met QC Criteria: May 17, 2010
• First Posted (Estimate): May 19, 2010

Study Record Updates

• Last Update Posted (Estimate): May 8, 2014
• Last Update Submitted That Met QC Criteria: May 7, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Otamixaban
• Other Study ID Numbers: POP6207; U1111-1116-8891 (Other Identifier: UTN)