E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary objective: To compare the efficacy and safety of adefovir dipivoxil (ADV) 10mg
with lamivudine (LAM) 100mg, once daily for 52 weeks in Japanese patients with
compensated chronic hepatitis B who have not been treated with antiviral medication.
For efficacy, to test the non-inferiority of ADV against LAM. |
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E.2.2 | Secondary objectives of the trial |
Secondary objective: To compare the efficacy of ADV in monotherapy in this study to
these in overseas studies (Studies GS-98-437 and GS-98-438). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Male or female patients aged ≥16 and <65, with serum HBV DNA ≥ 1 x 106 copies/mL at screening; serum alanine aminotransferase (ALT) level 50-500U/L at screening; with no mutation resistant to ADV and LAM at screening. |
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E.4 | Principal exclusion criteria |
Liver cancer (including both primary and metastatic); co-infection with HCV or HIV; autoimmune hepatitis (ex. antinuclear titer > 1:160) rather than chronic hepatitis B; a history of transplantation or having a plan for any transplantation; serious complication (e.g., cancer, serious cardiopulmonary disease, uncontrolled diabetes, alcoholism) other than hepatitis B; treatment with overdose NSAIDs, excluding temporary or topical use, within the past 7 days; receiving injection containing glycyrrhizin as the main component (e.g. monoammonium glycyrrhizinate/glycine/Lcystein hydrochloride) within the past 4 weeks; treatment with following drugs (except
ointment and/or cream etc.) within the past 8 weeks: drugs causing renal impairment, competitors of renal excretion (except temporary use), immunosuppressants, glucocorticoid preparations, drugs causing hepatic impairment; IFNs or HB vaccine within the past 24 weeks; a history of hypersensitivity to nucleoside analogues; pregnant, possibly pregnant or lactating females, or females who wish to be pregnant during the study period. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in serum HBV DNA level at Week 52 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1) Evaluation of HBV DNA level
• Percentage of patients with serum HBV DNA levels below the limit of
quantification (HBV DNA loss)
• Time to onset of serum HBV DNA loss
2) Evaluation of virus markers other than HBV DNA
• Percentage of patients with HBeAg loss
• Percentage of patients with HBeAg/Ab seroconversion
• Time to onset of HBeAg loss
• Time to onset of HBeAg/Ab seroconversion
• Percentage of patients with HBsAg loss
• Percenage of patients with HBsAg/Ab seroconversion
3) Liver function tests
• ALT level at Week 52 (distribution)
• Percentage of patients with normalized ALT
• Time to onset of ALT normalization
4) Rate of emergence of resistant virus at Week 52 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
No EOT definition in the protocol. Trial ended 52 weeks after subject’s first visit (+24 week follow up period for the 15 subjects who discontinued antiviral medication after 52 wk treatment period |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 4 |