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

Hepatic Impairment Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01126086
• Other study ID #: POP6207
• Secondary ID: U1111-1116-8891
• Status: Completed
• Phase: Phase 1
• First received: May 17, 2010
• Last updated: May 7, 2014
• Start date: May 2010
• Est. completion date: April 2011

Study information

• Verified date: May 2014
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: April 2011
• Est. primary completion date: April 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatic Impairment
• Liver Diseases

Intervention

Drug:
• otamixaban XRP0673
Pharmaceutical form: solution for injection Route of administration: intravenous

Locations

Country	Name	City	State
United States	Investigational Site Number 840002	Knoxville	Tennessee
United States	Investigational Site Number 840003	Miami Gardens	Florida
United States	Investigational Site Number 840001	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PK parameters including Ceoi, AUClast, AUC, C1min, CL, Vss, and t1/2z		Day 1 to Day 4	No
Primary	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	Yes
Secondary	Safety based on treatment-emergent adverse events, clinical laboratory evaluations, vital signs, and ECG		Screening (-28 days) up 8 to 11 days after treament	Yes