There has been speculation about the use of anti androgens for the treatment of ECs, this hypothesis warrants clinical investigation in light of our findings. Conclusions In summary, our results suggest a new mechanism for the development of EC, in which FOXA1 pathway signaling promotes tumor cell proliferation through AR and activates the Notch pathway by influencing AR expression. The newly identified FOXA1 AR interaction will help further eluci date the molecular mechanisms underlying EC progres sion and suggests that FOXA1 and AR are potential targets for EC treatment. COMBO I compares alirocumab against placebo, with patients permitted to receive other stable doses of LLTs in addition to maximally tolerated daily statin ther apy. COMBO II compares alirocumab versus ezetimibe when administered in conjunction with statin therapy only.
Methods Study design COMBO I is a Phase 3, randomized, double blind, placebo controlled, parallel group, multicenter, 52 week study being conducted at 76 sites in the USA. This study evaluates the efficacy and safety of alirocumab as add on therapy to stable, maximally tolerated doses of daily statin, with or without other stable LLT, in a planned population of 306 high risk patients with poorly controlled hypercholes terolemia. COMBO I began screening patients in July 2012 and completed collection of data in April 2014, data analyses are ongoing. COMBO II is a Phase 3, randomized, double blind, active controlled, parallel group, multinational 104 week study being conducted at 126 sites in Europe, Israel, North America, South Africa, and South Korea.
The planned population size is 660 high risk patients with poorly controlled hypercholesterolemia on stable, max imally tolerated daily statin therapy. This study began screening patients in August 2012 and is anticipated to complete in July 2015. Unlike COMBO I, with a placebo arm, COMBO II incorporates an active treatment arm with double dummy design and pa tients are not allowed to receive any other LLTs besides statin and their randomized treatment. The studies are being conducted in compliance with the principles laid down by the 18th World Medical As sembly and all applicable amendments laid down by the World Medical Assemblies and accord ing to the International Conference on Harmonization Guidelines for Good Clinical Practice.
The protocols have been reviewed and approved by the institutional review board of each participating center. All participants have provided written informed consent. Inclusion and exclusion criteria Principal selleck chem inclusion and exclusion criteria are shown in Table 1, full inclusion and exclusion criteria for both studies can be found in Additional file 1. All patients in COMBO I and II have hypercholester olemia and established CHD or CHD risk equivalents, with LDL C poorly controlled with a maximally toler ated daily dose of statin.