Safety concerns

The purpose of this study was to determine the safety and antiviral hepatitis B virus (HBV) activity of ACH126, 433 in the treatment of adults with lamivudine-resistant chronic hepatitis B.

Evaluation of the safety and antiviral activity of 3 dose levels of ACH126, 433 over a 12-week treatment in the population is described.

Inclusion Criteria

• Chronic HBV infection, known to be hepatitis B surface antigen (HbsAg) positive ≥ 6 months

• On lamivudine, either 100 or 150 milligrams daily for the treatment of chronic hepatitis B infection and exhibit a 2-3 log decrease in HBV deoxyribonucleic acid (DNA) levels followed by a rebound of at least 1.5 log HBV DNA or

  • Achieved an HBV DNA level of < 10,000 copies/milliliter (mL) HBV DNA on at least 2 occasions and have rebounded to > 100,000 copies/mL HBV DNA, or
  • Have a demonstrable lamivudine -resistant genotype regardless of treatment history.

• Hepatitis B e-antigen positive.

• Human immunodeficiency virus (HIV) negative.

• Serum alanine aminotransferase ≥ 1.5 and ≤ 10x times the upper limit of normal (ULN).

• Hemoglobin ≥ 10 grams/deciliter or hematocrit ≥ 30% (in the absence of blood transfusions or erythropoietin treatment in the preceding 2 weeks).

• Platelet count >75,000/cubic millimeters (in the absence of ongoing granulocyte colony-stimulating factor therapy).

• Serum creatinine < 1.1x the ULN.

• Negative radiologic screening test (ultrasound, computerized tomography scan, or magnetic resonance imaging) for hepatocellular carcinoma within 6 months prior to entry.

• Prothrombin time/international normalize ratio < 2.

• Participants of reproductive capability must utilize an approved form of birth control.

• All women of child-bearing capability must have a negative serum or urine pregnancy test (minimum sensitivity of 24 international units/liter of beta human chorionic gonadotropin) within 72 hours prior to the start of study medication.

• Participants must be able to provide written informed consent.

• Participant must be available for follow-up for a period of 20 weeks.

Exclusion Criteria

• HIV infection.
• Hepatitis C co-infection.
• Alcohol abuse.
• Pregnancy or breast-feeding.
• Inability to tolerate oral medication.
• Any clinical condition or prior therapy that, in the Investigator's opinion, would make the participant unsuitable for the study or unable to comply with the dosing requirements.
• Use of any investigational drug.
• Participants with decompensated liver disease.
• Use of any concomitant herbal treatments.