The overall reason for the Amendment INT-3 was to collect circulating tumor cells (CTCs) from all subjects on study in order to improve the power of the CTC sub-study.

The overall reason for the amendment INT-4 was: A prothrombin time (PT) was not done by many sites in Belgium, France, the Netherlands, and Spain, but an international normalized ratio (INR) was done instead. In addition, some subjects had abnormal but not clinically significant PT, which strictly per the current wording, would violate the protocol. This amendment allows an INR to be done whenever PT was not available. It also allows subjects with out of range PTs that were of no clinical significance to be eligible for the study.

The overall reason for the Amendment INT-5 was to incorporate the recommendations of the Data Review Committee (DRC) following their review of the efficacy and safety results from the protocol specified interim analysis of progression-free survival (PFS) (110 [50 percentage] of progression or death events).

The overall reason for Amendment INT-6 was about the final analysis of the primary endpoint, progression-free survival (PFS) was performed after the predefined total of 150 PFS events were reported in the abiraterone plus exemestane group and in the exemestane alone group; the clinical cutoff date for the final analysis (CCO-FA) was 20 September 2013. The results did not show a clinically meaningful or statistically significant advantage of abiraterone acetate plus exemestane or abiraterone acetate alone over exemestane alone. There was also a slight increase in the incidence of adverse events in subjects treated with abiraterone acetate or with the combination of abiraterone acetate plus exemestane versus single-agent exemestane. However, individual subjects might derive benefit from the treatment they are currently receiving with continued control of disease in the absence of significant toxicity. Therefore, it was decided to offer all subjects still on study treatment the opportunity to continue on their existing study medication for up to 2 years from the CCO-FA (ie, up to 20 September 2015), at which point the situation was reassessed for subjects still receiving study medication. Subjects who did not continue on study medication and those in long-term follow up were discontinued from the study. The decision to continue on study medication or withdraw from the study was made by the subject and the investigator.

The overall reason for Amendment International (INT)-7 was to extend the period for long-term safety follow up to a maximum of 5 years from the final analysis clinical cut off.