Safety and Efficacy Study of NVR 3-778 in Healthy Volunteers and Hepatitis B Patients

The Part I (Phase 1a) assessments of the dose-related safety and PK of NVR 3-778 in
volunteers will be conducted an established Phase 1 unit, which will facilitate the
overnight confinements and frequent safety assessments and blood sampling required for the
Part I evaluations. The Part II (Phase 1b) assessments of the dose-related safety, PK, and
initial antiviral efficacy of NVR 3-778 in hepatitis B patients will also be conducted at 4
different sites to meet enrollment goals of 72-84 chronic hepatitis B patients.

Study treatment in Parts I and II will be randomized and double-blinded. The volunteers in
each Part I dose cohort will be randomized 6:2 with active NVR 3-778 doses or matching
placebo doses. Similarly, study treatment for each cohort in Part II will be randomized 10:2
to treatment with active NVR 3-778 doses or matching placebo doses.

To promote objective safety and tolerance assessments during this trial, study subjects, and
site personnel administering the study drug and performing the clinical assessments on the
subjects, will be blinded to individual subjects' treatments assignments (active NVR 3-778
or placebo doses), for all treatment cohorts in the study. Study advancement to subsequent
volunteer cohorts in Part I and subsequent patient cohorts in Part II will require
satisfactory interim reviews of available cumulative safety data by the Part I and Part II
Safety Review Committees (SRCs), using the safety criteria and review procedures described
in the protocol. Also, there will be two interim reviews of safety data by an independent
Safety Monitoring Board (SMB), as described in the protocol.

Healthy volunteers may be male or female between 18 and 65 years old with a BMI of
18-32kg/m2. They must be in good health not have any health condition which could
interfere with the absorption, distribution or elimination of study drug, or with the
clinical and laboratory assessments in this study.

Patients enrolling in Part II of the study, may be male or female between 18 and 65 years
of age, with a BMI of 18-35kg/m2. Patients must have HBeAg positive, chronic hepatitis B
with no history of clinical decompensation, and must not have been treated for hepatitis B
before.