A Study of the Pharmacokinetics And Pharmacodynamics of Intravenously Administered Pegasys (Peginterferon Alfa-2a) in Patients With Chronic Hepatitis C And Previous Non-Response to Pegylated Interferon And Ribavirin Combination Therapy

Study Overview
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Brief Summary
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In this randomized, cross-over, open label study the correlation of Pegasys (peginterferon alfa-2a) pharmacokinetics after intravenous (iv) and subcutaneous (sc) administration with viral load and viral kinetics will be investigated in patients with chronic hepatitis C genotype 1 who were non-responders to previous standard combination therapy with pegylated interferon and ribavirin. Patients will be randomized to receive either weekly or twice weekly Pegasys iv or sc for 2 weeks, crossing over to the other mode of administration after a washout period of 6 weeks.

Official Title
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Pharmacokinetics and Pharmacodynamics of Intravenous Administration of Pegylated Interferon-2a in Patients With Chronic Hepatitis C and Previous Non-response to Standard Combination Therapy With Pegylated Interferon and Ribavirin (Intervention Study)

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: peginterferon alfa 2a [Pegasys]
* Drug: peginterferon alfa-2a [Pegasys]
* Drug: peginterferon alfa-2a [Pegasys]
* Drug: peginterferon alfa-2a [Pegasys]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult caucasian patients, 18 - 70 years of age Hepatitis C, genotype 1 Non-responder to previous anti-HCV therapy with peginterferon alfa and ribavirin Compensated liver disease (Child-Pugh class A) for >/= 24 months before baseline Positive for anti-HCV for > 6 months, with detectable serum HCV-RNA Exclusion Criteria: Treatment-naïve or responder to previous therapy HCV infection other than genotype 1 Positive for Hepatitis A, Hepatitis B or HIV infection at screening Chronic Hepatitis of other than HCV origin Decompensated liver disease (Child-Pugh class B or C) Therapy with systemic antiviral, antineoplastic or immunomodulatory agents in the 6 months prior to study Clinically relevant retina disorder Pregnant or lactating women and male partners of pregnant women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A/B<br> | Drug: peginterferon alfa 2a [Pegasys]<br>* sc weekly<br>Drug: peginterferon alfa-2a [Pegasys]<br>* iv weekly<br>|
| Experimental: C/D<br> | Drug: peginterferon alfa-2a [Pegasys]<br>* sc twice weekly<br>Drug: peginterferon alfa-2a [Pegasys]<br>* iv twice weekly<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HCV RNA levels (IU/ml, COBAS TaqMan HCV Test) in correlation with area under the plasma concentration-time curve (AUC) after sc and iv administration |  | 11 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of predictors of response to i.v. treatment |  | 11 months | 
| Effect of waist to hip ratio on pharmacokinetics |  | 11 months | 
| Effect of waist to hip ratio on viral response |  | 11 months | 
| Incidence of adverse events |  | 11 months |