To compare the bioavailability, pharmacokinetic profiles and the tolerability of two formulations of intravenous cyclosporine in healthy volunteers.
Participants were randomized into two treatment sequences: the test product followed by the reference product or vice versa. There was a washout period set to 14-21 days between the first and second treatment period. Through an indwelling IV cannula, the subjects received either 5 mg/kg NeuroSTAT® (test) or 5 mg/kg Sandimmune® (reference), infused at a constant rate over 4 h with a syringe pump. A total of 22 blood samples for Cyclosporine analysis were obtained pre-dose and at pre specified time points with last sample 48 h after start of infusion.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Masking
SINGLE
Enrollment
65
PAREXEL
Bloemfontein, South Africa
Bioequivalence between test and reference product.
To compare the bioavailability and pharmacokinetics of a single dose of the test product, NeuroSTAT® 5 mg/mL ready-to-use Cremophor® EL-free cyclosporine with the reference product, Sandimmune® Injection 50 mg/mL Cremophor® EL suspension (each 1 mL diluted in 20 mL saline). For this purpose the pharmacokinetics of cyclosporine was compared during and after intravenous (IV) infusion, over 4 hours, of a single dose of 5 mg/kg of each of the two formulations to healthy subjects. The primary parameters are area under the blood concentration-time curves (AUC) from time zero to time of last measurable concentration (AUC0-last), time zero to infinity (AUC0-∞), time 4 h to infinity (AUC4-∞). Point estimates and 90 % Confidence IntervaI (CI) for the NeuroSTAT®/Sandimmune® geometric mean ratios of all variables are calculated. The two products are considered bioequivalent if the 90 % CI for the primary variables are within the FDA and EMA approved range of 0.8 and 1.25.
Time frame: Repeated samplings from pre-dose to 48 hours
Tolerability comparison of test and reference product
To compare the tolerability profiles of the test product, NeuroSTAT® 5 mg/mL ready-to-use Cremophor® EL-free cyclosporine USP/Ph. Eur. lipid emulsion, with the reference product, Sandimmune® Injection (cyclosporine injection, USP) 50 mg/mL Cremophor® EL suspension (each 1 mL diluted in 20 mL saline). The proportions of overall adverse events and adverse events per organ class (as defined by the Medical Dictionary for Regulatory Activities) are compared between NeuroSTAT® and Sandimmune® by means of 95 % CI for the difference between paired proportions and p-values.
Time frame: From start of study drug administration to last blood sampling at 48 hours
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