Detection of serologic markers of hepatitis B virus (HBV) infection, as a function of time, in acute cases.
The Efficacy and Safety of Lamivudine in HBeAg-positive Chronic Hepatitis B
Enter
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Lamivudine is a Potent Inhibitor of HBV Replication
•A nucleoside analogue: (-)-2’,3’-dideoxy-3’-thiacytidine
•Antiviral activity against HBV and HIV
•Inhibits viral RNA-dependent DNA polymerase
Lamivudine has an Excellent Pharmacokinetic Profile
•Optimal dose is 100 mg once daily
•Rapidly absorbed
•Minimal liver metabolism
•Excreted unchanged in the urine
•Moderate to severe renal impairment requires dose reduction
•No significant drug interactions
What Patient Populations Have Been Studied
in Controlled Clinical Trials?
Primary
Compensated chronic hepatitis B (CHB) with
evidence of viral replication in treatment naïve patients
Others
•Pre-core mutant CHB
•Interferon failures
Key Lamivudine Clinical Studies (1)
Lai - Asia Pacific, placebo controlled NUCB3009 study (n=358)
- LAM100, LAM25 and PLB
Leung - Asia Pacific, placebo controlled NUCB3018 follow-on study to NUCB3009 (n=334)
- 3 and 4 years LAM100 vs 1 and 2 years LAM100
Dienstag - US placebo controlled study NUCA3010 (n=143)
- LAM100 and PLB
Key Lamivudine Clinical Studies (2)
Tassopoulos - EU placebo controlled study NUCB3014 in pre-core mutants (n=125)
- LAM100 and PLB
Schalm - |
EU active controlled study in |
NUCB3010 |
IFN naïve patients (n=230) |
- LAM100, IFN and LAM+IFN
Schiff - EU/US placebo controlled study NUCAB3011 in IFN failures (n=238)
- LAM100, PLB and LAM+IFN
Patient Entry Criteria
Patients had to have evidence of:-
•CHB - HBsAg +ve for at least 6m
•HBV replication - HBeAg +ve and HBV DNA +ve at screen and for 1m prior to screen
•Liver disease - elevated ALT 1.3xULN but < 10xULN in western studies; normal or elevated ALT in the Asian study
Lamivudine Rapidly Suppresses
Serum HBV DNA
10
0
Median -20
% Change -40
-60
-80
-100
Lamivudine
Placebo
Schiff
Dienstag
Lai
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Dienstag |
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Schiff |
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Lai |
0 |
10 |
20 |
30 |
40 |
50 |
Schalm |
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Study Week
Lamivudine Leads to HBeAg Seroconversion (HBeAg-, Anti-HBe+)
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Lai |
Dienstag |
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Schiff |
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Schalm |
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30 |
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*p<0.04 compared to placebo |
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29 |
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Patients |
25 |
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* |
21 |
20 |
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21 |
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(%) |
20 |
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* |
20 |
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17 |
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15 |
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13 |
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14 |
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10 |
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7 |
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6 |
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5 |
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Placebo |
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Lamivudine |
IFN |
Lamivudine |
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+ IFN |
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