Mallalieu 2014

Methods	Randomised clinical trial
Participants	35 participants Sex: 24 men, 11 women Mean age: 47.6 years Inclusion criteria: treatment‐naive male or female participants with chronic hepatitis C aged 18‐55 years, with a BMI of 18‐35 were eligible for a multicenter, double‐blind, randomised, placebo‐controlled study. Participants were required to have HCV genotype 1a or 1b infection, a serum HCV RNA concentration greater than 75,000 IU/mL, a serum ALT concentration under 5 times the ULN, and compensated liver disease. Exclusion criteria: participants with evidence of cirrhosis or decompensated liver disease were excluded, as were participants with a history of or current alcohol abuse, poorly controlled insulin‐dependent diabetes, unstable or poorly controlled asthma, congestive heart failure, unstable cardiopulmonary disease, renal disease, or seizure disorder. Eligible participants in all studies were required to have a negative urine drug screen, serum pregnancy test (if female), and to have a negative hepatitis B surface antigen test and anti‐HIV antibody test. Pregnant and breast feeding female participants were ineligible. Other exclusion criteria included donation of 4500 mL of blood within 30 days (participants with chronic hepatitis C).
Interventions	Experimental group: sequential cohorts of participants were randomly assigned to receive setrobuvir 200 mg, 400 mg, or 800 mg twice a day for 3 days. Control group: received placebo for 3 days.
Outcomes	Safety, kinetics, antiviral activity.
Notes	5 participants originally enrolled in cohort 2 (400 mg twice a day) were dosed incorrectly. These participants received setrobuvir 200 mg twice a day and were thus included with cohort 1 in the analysis. We emailed Mallalieu and colleagues on 26 April 2016 for additional information random sequence generation + allocation, participants completing the study, blinding 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	Described as double‐blinded but there was no further description of the placebo
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not described
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	It is unclear if any participants dropped out
Selective reporting (reporting bias)	Low risk	The trial reports all outcomes stated in the protocol (NCT00782353)
Vested‐interest bias	High risk	The trial was sponsored by a company that might have an interest in a given outcome (Hoffmann‐La Roche)
Other bias	Low risk	The trial appeared to be free of other components that could put it at risk of bias