Chronic Hepatitis C Infection MedDRA version: 8.1 Level: LLT Classification code 10008912 Term: Chronic hepatitis C
Conditions
Interventions
Product Name: ACH-0137171
Pharmaceutical Form: Tablet
Current Sponsor code: ACH-0137171
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-
Pharmaceutical form of
Sponsors
Achillion Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
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 experience specifically means prior 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. 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) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Subjects are not eligible for the following reasons: 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 (alpha-fetoprotein > 50 ng/mL), creatinine clearance = 80 mL/min (using Cockcroft-Gault equation), hemoglobin 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 will also be excluded.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To assess the short-term safety and tolerability of multiple, escalating, oral doses of ACH-0137171 in subjects with chronic hepatitis C infection. • To characterize the plasma pharmacokinetics of ACH-0137171 following administration of multiple, escalating, oral doses in subjects with chronic hepatitis C infection. • To assess the antiviral activity of ACH-0137171 as measured by plasma HCV RNA levels in subjects with chronic hepatitis C infection following administration of multiple, escalating, oral doses. • To assess the correlation between antiviral activity and pharmacokinetic parameters. ;Secondary Objective: • To perform viral dynamic and pharmacodynamic modeling of ACH-0137171 virologic response. • To assess the biochemical response to ACH-0137171 as measured by changes from baseline of serum ALT and AST levels. ;Primary end point(s): Safety will be evaluated by assessment of clinical laboratory tests at baseline and at various time points during the study, periodic physical examination, including vital signs and 12 lead ECG, and by the documentation of adverse events. Concomitant medication intake will also be reported. Antiviral activity will be evaluated by periodic measurement of plasma HCV RNA levels. Correlation of Cmax, Cmin, and plasma ACH-0137171 exposure (area under the curve [AUC]) will be attempted with maximal antiviral activity assessed by HCV RNA change from baseline and average area under the curve minus baseline (AAUCMB). The dose-response relationship for the anti-HCV activity of ACH-0137171 will be evaluated using a pharmacological (Emax) model, as described by the following equation: Antiviral Activity = (Emax x Dose)/(ED50 + Dose). Concentrations of ACH-0137171 will be determined in plasma using a validated bioanalytical assay and relevant pharmacokinetic parameters determined using standard non compartmental methods. Emax modeling (described above) will be applied to assess pharmacodynamic response. | — |
Countries
Germany
Outcome results
None listed