To test a hypothesized pharmacokinetic difference between the Test (Ne®) and Reference (Sigmasporin®) products to prove therapeutic equivalence in an open, multiple-fixed dose, one-way crossover, multicenter and multinational study over a period of 29 days. 42 stable renal transplant recipients maintained on Ne® were enrolled. Whole blood was collected at day 14 of the study at 0, 0.5, 1.0, 1.5, 2, 3, 4, 5, 6, 8, 10 and 12 hours after reference dosing and the same schedule was repeated at day 29 after switching on mg:mg basis to the test product at day 15 of the study. Analysis of variance was performed for the primary end-points of pharmacokinetic parameters AUC_0-12 and C_max of CyA using log-transformed values. Also tolerability was assessed as conveyed by vital signs, adverse events and laboratory investigations.
The 90% Confidence Interval (CI) test for the Ln-transformed, pharmacokinetic parameters was all within the FDA acceptable range of 80-125%, as Ln AUC_ss fail within the range of 92.56 – 103.55 and Ln C_max within the range of 85.73 – 103.58, the same also applied for AUC_0-4 that is considered the area of greatest inter and intra patient variability. Furthermore and in line with the newly adopted recommendation of the Expert Advisory Committee on Bioavailability and Bioequivalence of Health Canada, the 90% CI for AUC_ss was within the narrow range of 90-112%. No significant difference in tolerability was recorded between the two products. Sigmasporin Micr® (Julphar) was found to be bioequivalent and clinically interchangeable on mg: mg basis with Sandimmun Ne® (Novartis).