Ethical approval
The study was conducted according to the Declaration of Helsinki (1996), the International Conference on Harmonization Good Clinical Practice recommendations, and provisions of the German Medicines Act. The Ethical review committee—Ethikkommission des Landes Berlin, reference number 11/0570 ZS EK, approved the study protocol; final study approval by the German federal authority—Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM), reference number 61–3910-4037860, was granted on 04.04.2012. All amendments and other relevant study documentation were voted by the ethics committee and approved by the German federal authority BfArM: amendment 1 approved on 31.10.2012, amendment 2 approved on 27.05.2013, amendment 3 approved on 26.03.2014, amendment 4 approved on 09.03.2015 and amendment 5 approved on 13.04.2016.