HEPATITIS B VIRUS MedDRA version: 9.1 Level: LLT Classification code 10008910 Term: Chronic hepatitis B
Conditions
Interventions
Trade Name: Viread
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Tenofovir disoproxil fumarate
CAS Number: 147127-20-6
Other descriptive name: TDF
Concentration unit: mg milligram(s)
Co
Sponsors
Bristol-Myers Squibb International Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Signed Written Informed Consent 2) Subjects with chronic HBV infection (detectable HBsAg at screening and for at least 24 weeks prior to screening, or detectable HBsAg for =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 6 weeks after the last dose of investigational product. 2) Evidence of decompensated cirrhosis including but not limited to: variceal bleeding; hepatic encephalopathy; or ascites requiring management with diuretics or paracentesis; 3) Coinfection with HIV, hepatitis C virus ([HCV]; coinfection is defined as HCV Ab-positive with detectable HCV ribonucleic acid [RNA] by PCR), or hepatitis D virus (HDV). 4) Recent history of pancreatitis (within 24 weeks prior to the first dose of study medication); 5) Currently abusing illegal drugs or alcohol sufficient in the Investigator’s opinion, to prevent adequate compliance with study therapy or to increase the risk of hepatotoxicity or pancreatitis; 6) Other serious medical conditions that might preclude completion of this study or that require chronic administration of prohibited medications (see Exclusion Criteria 13 - 15). 7) Renal impairment that precludes subject from tolerating the per protocol study drug dose levels (see Protocol section 5.3.1). 8) Serum creatinine > 1.5 mg/dL; 9) Hemoglobin 100 ng/mL. 13) Known history of allergy to nucleoside or nucleotide analogues. 14) Except lamivudine, any prior therapy with nucleoside or nucleotide analogue antiviral agents with activity against hepatitis B (e.g., adefovir, entecavir, famciclovir, tenofovir/emtricitabine, clevudine); 15) Therapy with interferon, thymosin alpha or other immuno-stimulators within 24 weeks of randomization into this study; 16) Required chronic administration of medications which cause immunosuppression or which are associated with a high risk of nephrotoxicity or hepatotoxicity or which affect renal excretion. (See Protocol Section 5.5.1 for examples.). 17) Prisoners or subjects who are involuntarily incarcerated; 18) Subject who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease); 19) Unable to tolerate oral medication; 20) Poor peripheral venous access; 21) Off lamivudine therapy for greater than 7 days between the time of the screening visit and initiation of study treatment. Subjects may be re-screened twice (for a total of three screens) if it can be reasonably expected that study criteria will be met. However, beyond this, subjects should be reevaluated only after consultation with the study team.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the proportion of subjects in the entecavir plus tenofovir combination therapy group to the proportion of subjects in the treatment group receiving adefovir added to continuing lamivudine therapy who achieve HBV DNA 1 x ULN at baseline who achieve ALT normalization (= 1 x ULN) at Wk 48 & 96 -HBeAg+ at baseline with loss of HBeAg at Wk 48 & 96 -HbeAg+ at baseline with HBe seroconversion at Wk 48 & 96 -with HBsAg loss at Wk 48 & 96 -with HBs seroconversion at Wk 48 & 96 -with genotypic resistance based on analysis of samples from subjects with HBV DNA =50 IU/mL at Wk 48 & 96; •Mean log10 reduction from baseline in HBV DNA by PCR at Wk 48 & 96 •Frequency of AEs, SAEs, & discontinuations from study drug due to AEs or laboratory abnormalities ;Primary end point(s): Primary Efficacy Endpoints: • Proportion of subjects who achieve HBV DNA 1 x upper limit of normal (ULN) at baseline who achieve ALT normalization (= 1 x ULN) at Weeks 48 and 96; • Proportion of subjects who were HBeAg positive at baseline with loss of HBeAg at Weeks 48 and 96; • Proportion of subjects who were HBeAg positive at baseline with HBe seroconversion (HBeAg loss and presence of HBeAb) at Weeks 48 and 96; • Proportion of subjects with HBsAg loss and HBs seroconversion at Weeks 48 and 96; • Proportion of subjects with genotypic resistance based on analysis of samples from the subjects with HBV DNA = 50 IU/mL (approximately 300 copies/mL) at Weeks 48 and 96; Safety Endpoints: • Number and percent of subjects with adverse events (AEs), serious adverse events (SAEs), and discontinuations from study drug due to adverse events or laboratory abnormalities. | — |
Countries
Belgium, Germany, Italy
Outcome results
None listed