CHRONIC HEPATITIS B VIRUS,TREATMENT-NAIV MedDRA version: 8.1 Level: LLT Classification code 10019743 Term: Hepatitis B virus (HBV)
Conditions
Interventions
Trade Name: Baraclude
Product Name: Entecavir
Product Code: BMS-200475
Pharmaceutical Form: Oral solution
INN or Proposed INN: Entecavir
CAS Number: 209216-23-9
Current Sponsor code: BMS-200475-01
Oth
Sponsors
Bristol-Myers Squibb International Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Signed written informed consent 2) Nucleoside- and nucleotide-naïve subjects with chronic HBV infection (detectable HBsAg at screening and for at least 24 weeks prior to screening, or detectable HBsAg for = 3 g/dL (>= 30 g/L) • Serum total bilirubin == 172,000 IU/mL (approximately 1,000,000 copies/mL) by PCR at screening; OR For HBeAg-negative subjects, HBV DNA >=17,200 IU/mL (approximately 100,000 copies/mL) by PCR at screening; 5) ALT >= 1.3 x the ULN at screening and at least once >= 12 weeks prior to screening; 6) Males and females >= 16 years of age (or minimum age of consent in a given country) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=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) WOCBP using a prohibited contraceptive method. At this time there are no known contraindicated contraceptives to entecavir or tenofovir; 3) Women who are pregnant or breastfeeding; 4) Women with a positive pregnancy test on enrollment or prior to investigational product administration; 5) Sexually active fertile men not using effective birth control if their partners are WOCBP; 6) Evidence of decompensated cirrhosis including but not limited to: variceal bleeding; hepatic encephalopathy; or ascites requiring management with diuretics or paracentesis; 7) 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); 8) Recent history of pancreatitis (within 24 weeks prior to the first dose of study medication); 9) 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; 10) Other serious medical conditions that might preclude completion of this study or that require chronic administration of prohibited medications (see Exclusion Criterion 19); 11) Serum creatinine > 1.5 mg/dL; 12) Hemoglobin 100 ng/mL; • If the AFP level is between 21 and 100 ng/mL, it must be repeated prior to randomization. If the repeat AFP level is between 21 and 100 ng/mL, and if ultrasonography or computerized tomography (CT) of the liver performed prior to the first dose of study medication does not demonstrate a focal lesion suggestive of carcinoma, the subject may be dosed in the study; 16) Known history of allergy to nucleoside or nucleotide analogues; 17) Any prior therapy with nucleoside or nucleotide analogue antiviral agents with activity against hepatitis B (e.g., adefovir, entecavir, famciclovir, tenofovir, telbivudine, clevudine, emtracitabine), or any other experimental anti-HBV antiviral; 18) Therapy with interferon; thymosin alpha or other immuno-stimulators within 24 weeks of randomization into this study; 19) 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); 20)Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study; 21) Unable to tolerate oral medication; 22) Poor peripheral venous access.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the proportion of subjects in each treatment group who achieve HBV DNA =17,200 IU/mL at WK48 & 96 -with ALT normalization (=<1 x ULN) at WK48 & 96 -(HBeAg-positive at baseline) with loss of HBeAg at WK48 & 96 -(HBeAg-positive at baseline) with HBe seroconversion(HBeAg loss & presence of HBeAb) at WK48 & 96 -with HBsAg loss & HBs serconversion at WK48 & 96 *Mean log10 reduction from baseline in HBV DNA by PCR at WK48 & 96 *Frequency of AEs, SAEs & study drug discontinuations due to AEs/laboratory abnormalities *Evaluate ETV resistance profile in combination vs monotherapy | — |
Countries
France, Greece, Italy
Outcome results
None listed