No Effect of Pegylated Interferon Alfa-2b (PegIntron) on the Pharmacokinetics of Valopicitabine (NM 283) in Chronic HCV Patients

Valopicitabine (NM283) is a nucleoside analog exhibiting anti-HCV activity via inhibition of viral RNA polymerase, and is currently in phase II clinical development for the treatment of chronic hepatitis C.

In a Phase IIa trial, valopicitabine has shown potent anti-HCV activity in combination with pegylated interferon (Peginterferon alfa-2a [Pegasys]), with greater than 4.5 log10 serum HCV RNA reduction, and no viral resistance detected for study periods up to 6 months.

In that context, we are reporting pharmacokinetics (PK) of valopicitabine alone and in combination with Peginterferon alfa-2b (PegIntron).

Eligible treatment-naïve HCV-genotype 1-infected patients (18-65 yrs, with

compensated, chronic liver disease, ALT <5 ×ULN and serum HCV RNA >5 log10 IU/mL) were enrolled in this open-label trial and randomized to receive, at a 2:3 ratio, either valopicitabine monotherapy (n=12) or valopicitabine plus PegIFN a-2b (n=18).

Oral valopicitabine was administered once daily starting with 400 mg from day 1 to day 4, 600 mg from day 5 to day 7 and 800 mg thereafter.

PegIFN a-2b was administered by subcutaneous injection once weekly starting on day 8. Intensive steady-state PK sampling was performed over 8 hours on day 15 in all patients.

Results

• Values of steady-state PK parameters of valopicitabine were comparable when       valopicitabine was administered alone or in combination with peginterferon alfa-2b.
  
  
• Geometric mean ratio (combination vs. monotherapy) and associated 90% confidence interval were 0.95 for Cmax, 0.90 for AUC0-t, and 0.93 (0.81-1.06) for T1/2, indicating an absence of effect of co-administered peginterferon alfa-2b on the PK of valopicitabine.

The authors conclude, “Co-administration of PegIFN a-2b did not alter the pharmacokinetics of valopicitabine, providing pharmacokinetic support for combined use of valopicitabine with PegIFN in future clinical trials for the treatment of chronic HCV infection.”

11/14/05

Reference
X Zhou and others. Absence of Effect of Pegylated Interferon Alfa-2b on the Pharmacokinetics of Valopicitabine (NM283) in Patients with Chronic Hepatitis C. Abstract 66509. 56^th annual meeting of the American Association for the Study of Liver Diseases (56^th AASLD). November 11-15, 2005. San Francisco, CA.