Antiviral activity and safety of LB80380 in hepatitis B e antigen-positive chronic hepatitis B patients with lamivudine-resistant disease

[Guest guest]

Hepatology. 2009 Nov 30. [Epub ahead of print]

Antiviral activity and safety of LB80380 in hepatitis B e antigen-positive

chronic hepatitis B patients with lamivudine-resistant disease.

Yuen MF, Han KH, Um SH, Yoon SK, Kim HR, Kim J, Kim CR, Lai CL.

Department of Medicine, Queen Hospital, The University of Hong Kong, Hong

Kong.

We aimed to determine the antiviral activity and safety of a new nucleotide

analogue, LB80380, in chronic hepatitis B (CHB) patients with

lamivudine-resistant virus. Sixty-five patients with lamivudine-resistant virus

were randomized to receive five ascending daily doses (30, 60, 90, 150, 240 mg)

of LB80380. LB80380 was given together with lamivudine for the first 4 weeks,

followed by 8 weeks of LB80380 monotherapy. This was then followed by 24 weeks

of adefovir. Hepatitis B virus (HBV) DNA levels, serology, liver biochemistry,

and safety were monitored. The extent of the HBV DNA reduction at week 12 was

dose-dependent. The mean reduction from baseline was 2.81, 3.21, 3.92, 4.16, and

4.00 log(10) copies/mL for the five ascending dose groups. The

dose-proportionate effect was statistically significant (P < 0.001) with a

decrease of HBV DNA levels by an average of 1.54 log(10) copies/mL for every

1-unit increase in log(10) dose of LB80380. In 93.4% of patients, HBV DNA

decreased by>2 log(10) copies/mL, and 11.5% of patients had undetectable HBV DNA

levels (<300 copies/mL) by week 12. HBV DNA suppression was maintained during

the 24 weeks of adefovir treatment. Hepatitis B e antigen seroconversion and

normalization of alanine aminotransferase were seen in 14.6% and 24.6% of

patients, respectively, at week 12; 44.6% of patients experienced mild and

self-limiting adverse events, none of which were attributed to the study drug.

Conclusion: LB80380 at doses of up to 240 mg is safe, well tolerated, and

effective at reducing viral load in CHB patients with lamivudine-resistant virus

for a period of 12 weeks. (HEPATOLOGY 2010.).

PMID: 20091678 [PubMed - as supplied by publisher]

[Guest guest]

Hepatology. 2009 Nov 30. [Epub ahead of print]

Antiviral activity and safety of LB80380 in hepatitis B e antigen-positive

chronic hepatitis B patients with lamivudine-resistant disease.

Yuen MF, Han KH, Um SH, Yoon SK, Kim HR, Kim J, Kim CR, Lai CL.

Department of Medicine, Queen Hospital, The University of Hong Kong, Hong

Kong.

We aimed to determine the antiviral activity and safety of a new nucleotide

analogue, LB80380, in chronic hepatitis B (CHB) patients with

lamivudine-resistant virus. Sixty-five patients with lamivudine-resistant virus

were randomized to receive five ascending daily doses (30, 60, 90, 150, 240 mg)

of LB80380. LB80380 was given together with lamivudine for the first 4 weeks,

followed by 8 weeks of LB80380 monotherapy. This was then followed by 24 weeks

of adefovir. Hepatitis B virus (HBV) DNA levels, serology, liver biochemistry,

and safety were monitored. The extent of the HBV DNA reduction at week 12 was

dose-dependent. The mean reduction from baseline was 2.81, 3.21, 3.92, 4.16, and

4.00 log(10) copies/mL for the five ascending dose groups. The

dose-proportionate effect was statistically significant (P < 0.001) with a

decrease of HBV DNA levels by an average of 1.54 log(10) copies/mL for every

1-unit increase in log(10) dose of LB80380. In 93.4% of patients, HBV DNA

decreased by>2 log(10) copies/mL, and 11.5% of patients had undetectable HBV DNA

levels (<300 copies/mL) by week 12. HBV DNA suppression was maintained during

the 24 weeks of adefovir treatment. Hepatitis B e antigen seroconversion and

normalization of alanine aminotransferase were seen in 14.6% and 24.6% of

patients, respectively, at week 12; 44.6% of patients experienced mild and

self-limiting adverse events, none of which were attributed to the study drug.

Conclusion: LB80380 at doses of up to 240 mg is safe, well tolerated, and

effective at reducing viral load in CHB patients with lamivudine-resistant virus

for a period of 12 weeks. (HEPATOLOGY 2010.).

PMID: 20091678 [PubMed - as supplied by publisher]