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

Sponsor

Sanofi (Industry)

Overall Status

Completed

CT.gov ID

NCT01126086

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

8.3

Patients Per Site

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Hepatic Impairment	Drug: otamixaban XRP0673	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

25 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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.

Study Start Date :

May 1, 2010

Actual Primary Completion Date :

Apr 1, 2011

Actual Study Completion Date :

Apr 1, 2011

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigational Site Number 840003	Miami Gardens	Florida	United States	33169
2	Investigational Site Number 840001	Orlando	Florida	United States	32809
3	Investigational Site Number 840002	Knoxville	Tennessee	United States	37920

Sponsors and Collaborators

Sanofi

Investigators

Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Sanofi

ClinicalTrials.gov Identifier:

NCT01126086

Other Study ID Numbers:

POP6207
U1111-1116-8891

First Posted:

May 19, 2010

Last Update Posted:

May 8, 2014

Last Verified:

May 1, 2014

Additional relevant MeSH terms:

Liver Diseases

Otamixaban

Study Results

No Results Posted as of May 8, 2014