HEPSERA was also evaluated in an open-label, uncontrolled study of 467 chronic hepatitis B patients pre- (N=226) and post- (N=241) liver transplantation with clinical evidence of lamivudine- resistant hepatitis B virus (study 435). At baseline, 60% of pre-liver transplantation patients were classified as Child-Pugh-Turcotte score of Class B or C. The median baseline HBV DNA as measured by the Roche Amplicor Monitor PCR assay (LLOQ = 1000 copies/mL) was 7.4 and 8.2 log₁₀ copies/mL, and the median baseline ALT was 1.8 and 2.0 times the upper limit of normal in pre- and post-liver transplantation patients, respectively. Results of this study are displayed in Table 5. Treatment with HEPSERA resulted in a similar reduction in serum HBV DNA regardless of the patterns of lamivudine-resistant HBV DNA polymerase mutations at baseline. The significance of the efficacy results listed in Table 7 as they relate to clinical outcomes is not known.

Table 7. Efficacy in Pre- and Post-Liver Transplantation Patients at Week 48

Study 461 (Clinical Evidence of Lamivudine Resistance)

In study 461, a double-blind, active controlled study in 59 chronic hepatitis B patients with clinical evidence of lamivudine-resistant hepatitis B virus, patients were randomized to receive either HEPSERA monotherapy or HEPSERA in combination with lamivudine 100 mg or lamivudine 100 mg alone. At week 48, the mean ±SD decrease in serum HBV DNA as measured by the Roche Amplicor Monitor PCR assay (LLOQ = 1000 copies/mL) was 4.00 ±1.41 log₁₀ copies/mL for patients treated with HEPSERA and 3.46 ±1.10 log₁₀ copies/mL for patients treated with HEPSERA in combination with lamivudine. There was a mean decrease in serum HBV DNA of 0.31 ±0.93 log₁₀ copies/mL in patients receiving lamivudine alone. ALT normalized in 47% of patients treated with HEPSERA, in 53% of patients treated with HEPSERA in combination with lamivudine, and 5% of patients treated with lamivudine alone. The significance of these findings as they relate to clinical outcomes is not known.

Study 518 (Pediatric Study)

Study 518 was a double-blind, placebo-controlled, study in which 173 pediatric patients (ages 2 to < 18 years) with chronic hepatitis B (CHB) infection and elevated ALT were randomized 2:1 (115 receiving adefovir dipivoxil and 58 receiving placebo). Randomization was stratified by prior treatment and age -2- < 7 years old (cohort 1), 7- < 12 years old (cohort 2), and 12- < 18 years old (cohort 3). All patients in cohort 3 received 10 mg tablet formulation; all patients in cohorts 1 and 2 received an investigational suspension formulation (0.3 mg/kg/day cohort 1, 0.25 mg/kg/day cohort 2) once daily. The primary efficacy endpoint was HBV DNA < 1000 copies/mL plus normalization of ALT at the end of Week 48.

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