Boceprevir Pharmacokinetics

Boston—An analysis of clinical trials found that co-infected patients had a reduction in boceprevir exposure compared with mono-infected patients with hepatitis C. The authors noted the difference likely occurred because of an interaction between boceprevir and ritonavir-boosted HIV protease inhibitors.

In addition, the authors found no relationship between boceprevir pharmacokinetics and sustained virologic response (SVR) and concluded the reduction in exposure to boceprevir does not have a substantial impact on efficacy against the hepatitis C virus (HCV).

Results were presented at The Liver Meeting during a poster session. The poster was titled Assessment of Boceprevir (VICTRELIS^™) Pharmacokinetic/Pharmacodynamic Relationships for Sustained Viral Response (SVR) and Occurrence of Anemia: Results in HCV/HIV Co-Infected Patients and in Combined Mono- and Co-Infected Patients.

The FDA approved boceprevir in May 2011 to treat chronic hepatitis C genotype 1 infection in combination with peginterferon alfa-2a plus ribavirin. The oral medication, taken 3 times per day with food, was the first FDA-approved direct acting antiviral drug against HCV.

This analysis examined one phase 2 and two phase 3 studies. The phase 2 trial included 98 HCV/HIV-1 co-infected patients who were previously untreated for HCV. The first phase 3 trial included 1097 patients infected with HCV who had not received previous treatment, while the other phase 3 trial enrolled 403 HCV-infected, treatment experienced patients. The dosages were the same in each study: 1.5 µg/kg of peginterferon alfa-2b administered subcutaneously on a weekly basis, a weight-based dosing of ribavirin
(600-1400 mg) taken orally on a daily basis, and 800 mg of boceprevir 3 times daily every 7 to 9 hours.

In each study, the authors used a population pharmacokinetic model to estimate boceprevir pharmacokinetic parameters. They defined SVR for the phase 2 study as undetectable HCV RNA at 12 weeks post-therapy and for the phase 3 studies as undetectable HCV RNA at 24 weeks post-therapy. For all 3 studies, anemia was defined as at least 1 occurrence of hemoglobin <10 g/dL and severe anemia was at least 1 occurrence of hemoglobin <8.5 g/dL.

The authors said there was an association between lower boceprevir exposure and a reduced incidence of anemia. They also noted that researchers in the phase 2 trial did not collect the pharmacokinetics for boceprevir, and thus they could not rule out that the association was confounded by exposure to ribavirin, which influences the rate of anemia.

Further, the results were similar for all boceprevir pharmacokinetics parameters when measuring SVR and anemia. There was no statistically significant relationship between boceprevir pharmacokinetics parameters and SVR, which was similar to a previous analysis, according to the authors.

In the pooled analysis of all 3 trials, the probability of anemia decreased with a decrease in boceprevir pharmacokinetics, although there was not a similar finding with severe anemia. However, the authors noted the result for anemia was influenced by a small number of patients in the phase 2 study who had low boceprevir pharmacokinetics and no anemia.

For the phase 3 trials, the authors found no correlation between boceprevir pharmacokinetics and anemia.

This study was sponsored by Merck & Co, Inc.