A Study to Investigate the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of ACH-0137171 in Subjects With Chronic Hepatitis C Infection

This is a randomized, double-blind, placebo-controlled, dose escalation study of ACH-0137171
in subjects with chronic HCV infection.

Sequential cohorts of 10 subjects will be randomized (8:2) to receive multiple doses of
ACH-0137171 or placebo for 4 days (Days 1 through 4) with a single dose on Day 5 followed by
a complete pharmacokinetic profile. Dosing will be 300 - 600 mg administered either every 12
hours or every 6 hours (maximum daily dose of 2400 mg). All doses will be administered with
food.

The dose cohorts are as follows:

Study Schema:

Cohort 1: 300 mg ACH-0137171/placebo every 12 hours (600 mg/day)* Cohort 2: 300 mg
ACH-0137171/placebo every 6 hours (1200 mg/day)* Cohort 3: 600 mg ACH-0137171/placebo every
6 hours (2400 mg/day)*

A full review of all safety data will occur following each cohort. Depending on the data,
the Sponsor, in consultation with the Principal Investigator(s), may consider modifying the
planned dose escalation. The Sponsor may choose to interject an intermediate dose cohort
between 2 planned dose escalations or repeat a given dose level, or extend the dosing
period, or add an additional cohort. If a similar Grade 3 or 4 adverse event occurs in three
or more subjects, and is considered to be at least possibly related to study drug,
escalation to a higher dose will not occur.

Serial HCV RNA measurements, pharmacokinetic measurements of plasma concentrations of
ACH-0137171, and periodic safety monitoring will occur on Days 1 through 5. Additional HCV
RNA and PK measurements will be taken on Days 6 through 9. Follow up safety evaluations will
be completed out to 14 days after last study drug administration (i.e., on Days 12 and 19).

Inclusion Criteria:

- Chronic HCV infection must be documented by positive anti HCV antibody using a third
generation enzyme immunoassay (EIA) and persistent detection of HCV RNA in the blood
for at least 6 months. Subjects must be infected with HCV genotype 1 (line probe
assay; INNO-LiPA HCV II, Innogenetics) and may be treatment-naïve or
treatment-experienced (treatment experienced specifically means prior treatment with
interferon, standard or pegylated, with or without ribavirin with therapy stopped > 6
months prior to screening). In addition, eligible subjects must have ALT and AST < 5
x upper limit of normal (ULN), plasma HCV RNA> 5 log10 IU/mL, and have no clinical or
laboratory evidence of hepatic decompensation for inclusion (must have platelets
>100,000/mm3, total bilirubin < 1.5 x ULN, prothrombin time < 1.5 x ULN, or albumin >
3.0 g/dL for inclusion). Women are eligible if not pregnant or breast-feeding. Women
of childbearing potential (i.e., not surgically sterile or confirmed post menopausal)
must have confirmed negative pregnancy tests. All subjects must practice a medically
acceptable form of contraception described in Section 7.2.1.

Exclusion Criteria:

- HIV or HBV co-infection, known cirrhosis, prior history of clinical hepatic
decompensation (ascites, jaundice, encephalopathy or variceal hemorrhage), alcoholic
or other forms of chronic liver disease, evidence of hepatocellular carcinoma
(α-fetoprotein > 50 ng/mL), creatinine clearance < 80 mL/min (using Cockcroft-Gault
equation), hemoglobin < 10 g/dL, neutrophils < 1500/mm3, abnormal thyroid function
tests (TSH > 2.5 µIU/mL, free T4 > ULN), or, a positive test result for illicit
drugs, alcohol, or drug abuse within the past 12 months. Subjects who have
significant gastrointestinal, thyroid, renal, cardiovascular, pulmonary, oncologic,
or neurological disease, or who are currently receiving immunomodulators
(corticosteroids, etc), investigational, nephrotoxic or hepatotoxic drugs (e.g
phenytoin, carbamazepine, INH, azole anti-fungal agents such as ketoconazole, and
aminoglycoside antibiotics, etc.), non-steroidal anti-inflammatory agents, ibuprofen
or acetaminophen (on a daily basis) will also be excluded.