Lalezari 2013

Methods	Randomised clinical trial
Participants	81 adult participants Sex: 56 men, 25 women Mean age: 48 years Country: USA Inclusion criteria: male or female participants 18‐65 years old; documented clinical history compatible with chronic hepatitis C, including positive anti‐HCV antibody or presence of HCV RNA in the plasma for at least 6 months and liver biopsy within 24 months with histology consistent with chronic hepatitis C infection; HCV‐genotype 1, plasma HCV RNA> 5 log10 IU/mL; all participants agreed to use double‐barrier birth control (such as condom plus spermicide) from screening through at least 6 months after the last dose of the study drug. Exclusion criteria: pregnancy or breastfeeding; BMI > 35 kg/m2; co‐infection with HBV or HIV; history or evidence of decompensated liver disease; prior clinical or histological evidence of cirrhosis; ALT or AST level > 3 ULN; histology of HCC or findings suggestive of possible HCC; 1 or more additional known primary or secondary causes of liver disease, other than hepatitis C, previous antiviral treatment for HCV; current abuse of alcohol or illicit drugs; current use of any major inhibitor or inducer of cytochrome P450 3A4 or any other investigational drugs within 30 days of dosing, or other clinically significant diseases that, in the opinion of the investigator, would jeopardise the safety of the participants or affect the validity of the study results.
Interventions	Experimental groups: oral rising daily doses of 50, 100, 150 or 200 mg of IDX184 for 2 weeks. Control group: placebo. Co‐intervention: peg‐IFN‐ α 2a and RBV for 2 weeks. All participants received additional 2 weeks of peg‐IFN and RBV.
Outcomes	HCV RNA, Safety, pharmacokinetics.
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	High risk	Despite being a double‐blinded study, there were different doses, syringes plus capsules, different administrations – once vs twice
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not described
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	The number of dropouts was unclear
Selective reporting (reporting bias)	High risk	Not all outcomes stated in the protocol were assessed (NCT01011166 )
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