Figure 1.

Both clinical studies were open label with no randomization. In the phase 1 study (A), the sequence of treatment was Advate first, followed by BAX 855 for each subject in each cohort. Nine subjects in the 30 IU/kg group were treated first. After review of the data from the first cohort and approval by the Data Monitoring Committee, treatment of 10 subjects in the 60 IU/kg group commenced. Only 1 treated subject was excluded from the PK analysis set as a result of a bleeding episode within 4 days of infusion. In the pivotal study (B), treatment assignment depended on the subjects’ prior treatment: Subjects previously receiving prophylaxis were assigned to the prophylaxis group. The first 17 subjects who previously received on-demand treatment were assigned to the on-demand group, then additional subjects were assigned to the prophylaxis arm. The PK subset comprised 26 subjects in the prophylaxis group. Twelve subjects discontinued during prophylaxis: 1 for a surgical procedure, 1 because of screen failure, 2 because of discontinuation by the subject, 4 because of an adverse event, and 4 for protocol violation.