Currently, less frequent than once weekly subcutaneous epoetin administration regimens were
shown to be equally effective and safe as the once-weekly schedules in stable pre-dialyzed
and peritoneal dialyzed patients Bioequivalence of once-every-two-weeks and once-weekly
subcutaneous administration of the same total dose of epoetin beta for the maintenance phase
of anemia treatment in stable, iron-replete, chronic hemodialyzed patients was therefore
prospectively investigated.
two treatment schedules will be considered equivalent if the primary efficacy parameters will
be simultaneously similar for both groups and in the predefined range of variation.
Confidence intervals (CIs) will be used to compare groups. Since the target Hb in dialyzed
patients is defined as 11g/dL (110 g/L) by the European Guidelines and as >10 g/dL (100 g/L)
by the National Guidelines, with a recommended upper limit of 13 g/dL (130 g/L), the efficacy
range for Hb in this study was predefined as 10-12 g/dL (100-120 g/L). The two treatment
schedules will be considered to have similar efficacy if the mean Hb in Group 2w will not
differ by more than ±0.5 g/dL (±5 g/L) compared to Group 1w during the assessment period.
Once similar efficacy established, drug requirements will be compared calculating the ratio
of the mean weekly epoetin doses in Group 2w/Group 1w. A range of 0.8 to 1.25 for the ratio
is considered sufficient to define bioequivalence. Equivalence of drug usage in the two arms
will be accepted if the whole 95% CI for this ratio will be within the above limits.
Lack of difference between group means does not imply similar distribution of treatment
effects within each group. The individual hemoglobin change will be used to assess if
response to treatment was similarly variable in the two arms. The change in Hb will be
calculated for each patient as the difference between the mean Hb during the assessment
period and the mean Hb during the baseline phase.