Lawitz 2013b

Methods	Randomised clinical phase I, multicentre trial
Participants	44 participants Sex: 32 men, 9 women Median age: 49 years Country: USA Inclusion criteria: 18‐65 years of age and had chronic HCV 1a or 1b and plasma HCV RNA > 5 log10 IU/mL at screening. Participants were HCV treatment‐naive and had a BMI of 19‐35 kg/m2 inclusive, creatinine clearance > 60 mL/min and a QTcF interval < 450 ms. Exclusion criteria: cirrhosis, hepatic decompensation, excessive ongoing alcohol intake, Gilbert's syndrome, evidence of HCC, co‐infection with HIV or HBV, ALT or AST levels > 5 x ULN, total bilirubin > ULN, haemoglobin < 11 g/dL, or absolute neutrophil count 1000 cells/mm2 (750 cells/mm2). Concomitant prescription during the study unless prior approval was received from the medical monitor. Participants using hormonal contraception were required to employ 2 additional barrier methods of contraception.
Interventions	The trial divided into 4 cohorts, and randomised to experimental group or control group Experimental group: oral 60 mg, 200 mg (genotype 1a), 200 mg (genotype 1b), or 400 mg of GS‐9451 once daily for 3 days. Control group: placebo.
Outcomes	Antiviral response, sequence analyses, pharmacokinetics, safety assessment.
Notes	We emailed Lawitz and colleagues on 26 April 2016 for additional information on allocation, blinding (placebo pill), protocol 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	It was described that all were blinded, however it was not stated if there were any similarities between the placebo pill and intervention
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	It was described that all were blinded, however it was not stated if there were any similarities between the placebo pill and intervention
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	There were above 5% dropouts. 3 participants were not included in the efficacy analyses. In addition, 3 participants were withdrawn after enrolment and not included in any analysis due to unknown reasons. It was unclear how the trial handled missing data.
Selective reporting (reporting bias)	Unclear risk	No protocol could be obtained
Vested‐interest bias	High risk	The trial was funded by Gilead Sciences
Other bias	Low risk	The trial appeared to be free of other components that could put it at risk of bias