Hinrichsen 2004

Methods	Randomised clinical trial
Participants	51 adult participants Sex: 41 men, 10 women Mean age: 47.8 years Countries: Germany, France, and Spain. Inclusion criteria: women or men aged 18 years or older with chronic genotype 1 HCV infection. The line probe assay was used to determine the genotype of the viral infection. A liver biopsy specimen showing changes consistent with chronic HCV infection had to have been performed within the previous 12 months. At screening, the HCV load had to be 50,000 copies/mL serum. Exclusion criteria: women were excluded if they were breast‐feeding or at risk of pregnancy; men had to use an adequate form of contraception if their partner was of childbearing potential. They were not enrolled if there were other or additional reasons for chronic liver disease, including the presence of other hepatitis‐causing viruses and/or a history of alcohol abuse within the previous 12 months and/or evidence of Child’s B or C liver disease at screening. No other antiviral or antimicrobial or investigational therapies were allowed during the study (screening, pretreatment, and treatment phases). Patients were excluded if, at screening, their baseline ALT/AST) plasma levels exceeded the ULN by more than 5‐fold (5 times the ULN) or their total bilirubin or alkaline phosphatase levels were 1.5 times the ULN. Other exclusion criteria included co‐infection with HIV, a platelet count 100,000/mm3, a white blood cell count 2000 cells/mm3, any clinically significant laboratory abnormalities, and a positive test result for illicit or nonprescription drugs.
Interventions	The trial was divided into 3 different cohorts, according to grade of liver disease (Ishak score, Metavir score). Experimental group: 2 days of oral 25 mg, 200 mg or 500 mg of BILN‐2061 in participants with Ishak score 0‐2. Oral 200 mg of BILN 2061 in participants with Ishak score 3‐4. Oral 200 mg of BILN 2061 in participants with Ishak score 5‐6. Control group: placebo.
Outcomes	Virologic efficacy, pharmacokinetics, safety assessment.
Notes	We emailedWe emailed Hinrichsen and colleagues on 21 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	The trial was described as being double‐blinded but it was unclear how the blinding was performed
Incomplete outcome data (attrition bias) All outcomes	Low risk	0 participants dropped out
Selective reporting (reporting bias)	Unclear risk	No protocol could be obtained for all 3 stages, and the clinicalTrials.gov information was added after completion
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