Sample size calculation
The sample size calculation was based on the primary endpoint, as well as the ALT change from baseline; the latter being the biomarker with the least favourable ratio of anticipated effect size to variance. A sample size of 108 patients with an allocation ratio of 2:1:1:1:2 for placebo, BI 1467335 1 mg, 3 mg, 6 mg or 10 mg, with an assumed 10% discontinuation rate and assumed maximum change of 30%, was anticipated to provide sufficient precision for the primary endpoint evaluation as well as an 84.8% probability of detecting a 20% relative change from baseline in ALT at Week 12. This calculation was based on 1000 simulations using Multiple Comparison Procedure—Modelling (MCPMod)