Study of the Pharmacokinetic Action of Amantadine and Ribavirin in Chronic Hepatitis C. CINAM - Full Text View

Sponsors and Collaborators:	University Hospital, Limoges Laboratoire Roche
Information provided by:	University Hospital, Limoges
ClinicalTrials.gov Identifier:	NCT00199719

Purpose

Peg interferon and ribavirin currently represent the standard approved association for treating patients infected with hepatitis C virus (HCV) . The adjunction of amantadine is expected to gain about 10 % of sustained virological response (SVR) . Unfortunately, about 50 % of the patients remain relapsers or virological non responders. The main predictive factors of SVR are HCV genotype and body weight (BW). The impact of the drug pharmacological properties, particularly those of ribavirin requires complementary studies. This drug has a large distribution volume and its concentrations display large inter-individual variability. Two studies performed in HCV patients found no correlation between ribavirin dose adjusted on BW and a single ribavirin time point serum concentration at steady state.

The aim of this study is to investigate the pharmacokinetic-pharmacodynamic relationships of ribavirin in hepatitis C patient

Condition	Intervention	Phase
Chronic Hepatitis C	Drug: Ribavirine	Phase II

MedlinePlus related topics: Hepatitis Hepatitis C

Drug Information available for: Ribavirin Peginterferon Alfa-2a Amantadine Amantadine hydrochloride Amantadine sulfate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Pharmacokinetics/Dynamics Study
Official Title:	Study of the Pharmacokinetic Action of Amantadine and Ribavirin in Chronic Hepatitis C Non 2 -3 Genotype naïve Patients Treated With a 12 Weeks Bitherapy of Peginterferon Alpha 2a-Ribavirin, and Followed by a Tritherapy of Peginterferon Alpha 2a-Ribavirin-Amantadine for 36 Weeks

Further study details as provided by University Hospital, Limoges:

Primary Outcome Measures:

-Study of the complete pharmacokinetics of ribavirin at day 1, and day 84 (week 12).
-Study of the complete pharmacokinetics of amantadin and ribavirin at week 12 + one day and at week 24

Enrollment:	30
Study Start Date:	June 2003
Study Completion Date:	September 2006

Detailed Description:

The study is conducted in naive patients infected with genotype non 2 non 3 administered peginterferon alpha 2-a (40KD) weekly, and ribavirin with dose adjusted on BW (< 75 kg 1000 mg/day, >75 kg 1200 mg/day) for the first three months with adjunction of amantadine 200 mg daily for the following 9 months.

Plasma concentration profiles of ribavirin were studied after the first dose (D0) and at W12. At each period, blood samples were collected pre-dose and 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, and 10 hours post-dosing. Ribavirin concentrations were measured using liquid chromatography-tandem mass spectrometry and ribavirin area under the concentration-timcurves (AUC0-10h) were derived from plasma concentrations profiles using the linear trapezoidal rule.

Virological follow-up was performed at W2, W4, W6, W8, W12, W24 and W72. Early virological response was defined by undetectable viral load at W12.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Male and female patients >18 years of age and <65 years of age
Génotype non2 non3
Chronic liver disease consistent with chronic hepatitis C infection on a biopsy (obtained within the past 24 months) as judged by a local pathologist (Metavir >A1and >F1)
Negative urine or blood pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of study drug

Exclusion Criteria:

Women with ongoing pregnancy or breast feeding
IFN or ribavirin therapy at any previous time
Positive test at screening for anti-HAV IgM Ab, HBsAg, anti-HBc IgM Ab, anti-HIV Ab
History or other evidence of a medical condition associated with chronic liver disease other than HCV (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures)
Serum creatinine level >1.5 times the upper limit of normal at screening
History of severe psychiatric disease, especially depression

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00199719

Locations

France
Service d'Hépatogastroentérologie
Limoges, France
Service d'Hépato-gastroentérologie
Angers, France

Sponsors and Collaborators

University Hospital, Limoges

Laboratoire Roche

Investigators

Principal Investigator:

Véronique LOUSTAUD-RATTI, MD

University Hospital, Limoges

More Information

Study ID Numbers:	I02022
Study First Received:	September 14, 2005
Last Updated:	October 30, 2007
ClinicalTrials.gov Identifier:	NCT00199719
Health Authority:	France: Afssaps - French Health Products Safety Agency

Keywords provided by University Hospital, Limoges:

drug monitoring
ribavirin-pharmacokinetic
pharmacodynamics
chronic hepatitis C
non 2 non 3 genotype

Study placed in the following topic categories:

Virus Diseases
Hepatitis
Liver Diseases
Dopamine
Digestive System Diseases
Hepatitis, Chronic

Ribavirin
Peginterferon alfa-2a
Hepatitis, Viral, Human
Hepatitis C
Amantadine
Hepatitis C, Chronic

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
RNA Virus Infections
Neurotransmitter Agents
Flaviviridae Infections
Molecular Mechanisms of Pharmacological Action
Anti-Dyskinesia Agents
Physiological Effects of Drugs
Antiparkinson Agents

Antiviral Agents
Pharmacologic Actions
Sensory System Agents
Analgesics, Non-Narcotic
Therapeutic Uses
Dopamine Agents
Peripheral Nervous System Agents
Analgesics
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 15, 2009