Lalezari 2012

Methods	Randomised clinical trial
Participants	41 adult participants Sex: 29 men, 12 women Mean age: 48 years Country: USA Inclusion criteria: male or female adults 18‐65 years of age, inclusive; a documented clinical history compatible with chronic hepatitis C, including the presence of HCV RNA in the plasma for least 6 months and a liver biopsy sample within 24 months with histology consistent with chronic HCV infection; HCV genotype 1, plasma HCV RNA > 5 log10 IU/ml, and anti‐HCV antibody positive at screening; and agreement by participants to use a double‐barrier method of birth. Sex: 29 men, 12 women. Exclusion criteria: BMI > 32 kg/m2; pregnancy or breastfeeding; co‐infection with HBV or HIV; history or evidence of decompensated liver disease; history of HCC or findings suggestive of possible HCC; other causes of liver disease; previous antiviral treatment for HCV infection; current abuse of alcohol or illicit drugs or treatment for opioid addiction; use of any known inhibitor and/or inducer of CYP 3A4 or any other investigational drugs within 30 days of dosing; abnormal laboratory values at screening (a hemoglobin level < 12.0 g/dl for males or < 11.0 g/dl for females; an absolute neutrophil count < 1.5 × 109/liter; a platelet count < 130 × 109/liter; an alanine aminotransferase [ALT] or aspartate aminotransferase [AST] level > 2.5 × upper limit of normal [ULN]; an alkaline phosphatase level > 1.25 × ULN; an albumin level < 3.5 g/dl; total bilirubin, amylase, lipase, or international normalized ratio [INR] > ULN; a serum creatinine or blood urea nitrogen value > ULN; creatinine clearance < 80 ml/min as estimated by the Cockcroft‐Gault formula; or any other laboratory abnormality > grade 1, except for asymptomatic cholesterol or triglycerides); or other clinically significant diseases that, in the opinion of the investigator, would jeopardize the safety of the patient or impact the validity of the study results.
Interventions	Experimental group: oral 25 mg, 50 mg, 75 mg, 100 mg of IDX184 for 3 days. Control group: placebo. Co‐intervention: 14 days after treatment the participants were offered extended therapy with peg‐IFN/RBV.
Outcomes	Safety assessment, antiviral activity.
Notes	We emailed Lalezari and colleagues on 26 April 2016 for additional information but reply not received yet.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not described
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	The trial was described as being double‐blinded but it was unclear how the blinding was performed
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Only some outcomes were blinded for outcome assessors
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	No dropouts
Selective reporting (reporting bias)	Unclear risk	No protocol could be obtained
Vested‐interest bias	High risk	The trial was funded by Idenix pharmaceuticals Inc
Other bias	Low risk	The trial appeared to be free of other bias domains that could put it at risk of bias