Chronic Hepatitis B
Conditions
Brief summary
To demonstrate the dose response of entecavir in Japanese patients as measured by HBV DNA levels by PCR (log10 copies/mL) at Week 22
Interventions
DRUGEntecavir
Capsule, P.O., 0.01, 0.1 or 0.5 mg, once daily for 24 weeks
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Positive for HBsAg OR, negative for IgM core antibody and confirmation of chronic hepatitis B on liver biopsy, * Positive for HBeAg OR negative for HBeAg with positive HBeAb, * Documented HBV Viremia on 2 or more occasions: Viremia on sample drawn AND HBV DNA of ≥ 40 MEq/mL by Quantiplex assay at the screening visit
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Mean change from baseline in HBV DNA levels as measured by by PCR (log10 copies/mL) | at Week 22 |
Secondary
| Measure | Time frame |
|---|---|
| Incidence of laboratory abnormalities in each entecavir group in comparison to lamivudine | Through Week 24 (end of dosing) plus 5 days |
| HBV DNA as measured by PCR (log10 copies/mL) at Week 22 [to demonstrate non-inferiority of at least one dose of entecavir as compared with lamivudine] | Week 22 |
| Proportion of subjects in each treatment group who achieve HBV DNA reduced by ≥2 log10 and/or below the limit of quantification (LOQ) (<400 copies/mL) as measured by PCR assay | Week 12, Week 22 |
| Proportion of subjects in each treatment group who achieve HBV DNA below the limit of detection (0.7 MEq/mL) of the Quantiplex branched DNA hybridization assay (Quantiplex assay) | Week 22 |
| Proportion of subjects in each treatment group who achieve normalization of ALT (ALT <1.25 x UKN) | Week 22 |
| Incidence of clinical adverse events and discontinuations due to adverse events in each entecavir group in comparison to lamivudine | Through Week 24 (end of dosing) plus 5 days |
| Proportion of subjects in each treatment group who achieve seroconversion at Week 22 among of HBeAg-positive subjects at baseline | Week 22 |
| Proportion of HBeAg-positive subjects at baseline who achieve responder status (defined as: HBV DNA <0.7 MEq/mL by the Quantiplex assay; loss of HBeAg and normal serum ALT) | Week 22 |
| Proportion of HBeAg-negative subjects at baseline who achieve responder status (defined as HBV DNA <0.7 MEq/mL by the Quantiplex assay and normal serum ALT) | Week 22 |
| Incidence of genotypic resistance of HBV isolates in subjects who have a ε 1 log10 increase in HBV DNA as measured by PCR assay after achieving the lowest value while on study drug | Through Week 24 |
| Relationship of HBV isolates (genotypes A, B, C etc) at baseline compared to response | Week 22 |
| Proportion of subjects in each treatment group who achieve loss of HBeAg at Week 22 among HBeAg-positive subjects at baseline | Baseline, Week 22 |
Outcome results
None listed