Clarified in page 18 that highly effective contraception methods included total abstinence(when this was in line with the preferred and usual lifestyle of the subject). Whereas periodic abstinence e.g. calendar, ovulation, symptothermal, post-ovulation and withdrawal were not acceptable methods of contraception. Clarified in page 25 that results from routine blood laboratory evaluation directly assessed before Treatment (i.e. within 24h prior to Treatment) was used instead of further baseline laboratory evaluation. No second assessment implying second drawing of venous blood was to be done. Appendix 4: updated on drugs that may alter tacrolimus concentrations. Appendix 7: visual faculty test- clarified if the investigator suspected neurological symptoms visual faculty test was to be performed. According to investigator’s opinion to guarantee patients safety detailed neurological diagnostics conducted by a qualified person (e.g. neurologist) was to be performed. Page 49 Sample Size Calculation: Clarified that since the primary objective in Phase I of this study is the PK-analyses, the number of 27 patients in each arm was required for the PP-PK Set. Randomization was continued until this number of patients was available with complete and evaluable PK-measurements. At the time of this amendment, the drop-out rate was about 30%, that required about 40 patients/arm (= 80 total instead of 30 patients/arm) to be randomized into this study for Phase I. All patients enrolled for phase I of the study were to be included in the total sample size for phase II of the study, given the study continued into phase II.

In response to German Health Authority’s request, the protocol was modified to implement most recent notifications for use of MPA based on the dear health care professional letter (DHCPL) that was sent out for CellCept by Roche on 12 Dec 2014. In detail the study medication stopping rules were adopted to clearly follow the recommendations given in the DHCPL. This information was added to Sections 6.6.3 and toAppendix 16.1.1-Protocol-Appendix 5.

Phase II of the study was not to be started, rationale for this decision was the high patient drop-out rate and an associated long recruitment timespan. Eighty-one patients were recruited to Phase I and only 45 of the required 54 patients were available for PK analysis. To complete Phase II, 245 (in addition to 81) patients were to be required to achieve calculated sample size. Therefore the protocol was amended to stop recruitment and analyze Phase I patient data of CERL080ADE27 (PK-Phase I). Patients that were still ongoing were scheduled for an end of study (EOS) visit. During this visit patients were informed by the investigator about the endof study and advised about further treatment course.