Randomized, open-label, comparative phase IV study on the bioavailability of Ciclosporin Pro (Teva) versus Sandimmun® Optoral (Novartis) under fasting versus fed conditions in patients with stable renal transplants

Gäckler, Anja GND; Dolff, Sebastian GND; Rohn, Hana GND; Korth, Johannes GND; Wilde, Benjamin GND; Eisenberger, Ute GND; Mitchell, Anna GND; Kribben, Andreas GND; Witzke, Oliver GND

Background: The influence of pre- or postprandial administration on pharmacokinetics of cyclosporine is supposed to be less in gel-based formulations than in microemulsions. This study was designed to investigate the influence of a high-fat meal on the pharmacokinetic profile of the two cyclosporine containing formulations Ciclosporin Pro (gel-based emulsion) and Sandimmun® Optoral (microemulsion) in renal transplant recipients.
Methods: A randomized, open-label, repeated-measurement, comparative phase IV trial was conducted with two sequence groups for nutrition condition (fasting→fed, fed→fasting) and two treatment phases (Sandimmun® Optoral → Ciclosporin Pro), each covering both nutrition conditions. Primary pharmacokinetic variable of interest was the reduction of bioavailability due to high-fat food compared to fasting conditions measured by the difference D of ln-transformed bioavailability variables (AUCSS, τ, Css, max, und Css, min).
Results: A nutrition effect was found for both study medications with respect to the parameters AUCSS, τ and Css, max, but not to Css, min. The reduction of bioavailability caused by high-fat food was not significantly different for Sandimmun® Optoral and Ciclosporin Pro.
Conclusions: An effect of high-fat breakfast prior to the morning dose on AUCSS, τ and Css, max was found for Sandimmun® Optoral and for Ciclosporin Pro. Trough level monitoring did not capture ingestion-related variability. Conversion to Ciclosporin Pro seems to be safe with regard to intra-individual pharmacokinetic variability.

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Gäckler, A., Dolff, S., Rohn, H., Korth, J., Wilde, B., Eisenberger, U., Mitchell, A., Kribben, A., Witzke, O., 2019. Randomized, open-label, comparative phase IV study on the bioavailability of Ciclosporin Pro (Teva) versus Sandimmun® Optoral (Novartis) under fasting versus fed conditions in patients with stable renal transplants. https://doi.org/10.1186/s12882-019-1340-z
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