Larrey 2012

Methods	Randomised phase I clinical trial
Participants	27 participants Sex: 21 men, 6 women Mean age: 46 years Countries: France, Germany, and Switzerland. Inclusion criteria: treatment‐naive participants male or female (with documented hysterectomy or postmenopausal), 18–70 years of age, had chronic hepatitis C infection of genotype‐1, with a HCV viral load > 100,000 IU/mL at screening. Exclusion criteria: cirrhosis was ruled out by biopsy or elastometry (FibroScan; cut‐off used by investigators ranged from 12.5 to 16.0 kPa) performed within 24 months prior to study enrolment. Participants with HBV or HIV co‐infection, concurrent liver disease other than HCV, past treatment with any experimental polymerase inhibitor, or hyperbilirubinaemia (> 1.5 ULN not due to Gilbert’s polymorphism).
Interventions	Experimental group: oral 400 mg, 600 mg, or 800 mg 3 times daily of BI 207127 for 28 days. Control group: placebo. Co‐intervention: peg‐IFN α‐2a was administered subcutaneously at a dose of 180 lg per week, and RBV was given orally at a dose of 1000 mg per day (body weight < 75 kg) or 1200 mg per day (body weight > 75 kg) in 2 divided doses. Participants were advised to use sun protection. After 4 weeks, participants were given the opportunity to continue peg‐IFN α‐2a or 2b and RBV up to week 48 at the investigators' discretion.
Outcomes	Efficacy assessment, safety assessment, drug resistance monitoring, HCV RNA, PK assessment.
Notes	NCT00905632 Only treatment‐naive participants received placebo, and could be used in the analyses. We emailed Larrey 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	Described as being double‐blinded but it was unclear how the blinding was performed
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Described as being double‐blinded but it was unclear how the blinding was performed
Incomplete outcome data (attrition bias) All outcomes	Low risk	No participants in the treatment‐naive group were lost to follow‐up
Selective reporting (reporting bias)	Low risk	All outcomes stated in the protocol (NCT00905632) were assessed
Vested‐interest bias	High risk	The trial was funded by Boehringer Ingelheim
Other bias	Low risk	The trial appeared to be free of other components that could put it at risk of bias