The bioequivalence of liquid and freeze-dried formulations of recombinant human chorionic gonadotrophin

Abstract

Objective: To compare the bioavailability and tolerability of liquid and freeze-dried formulations of recombinant human chorionic gonadotrophin (r-hCG).Subjects and methodsZ In an open-label, randomised, single-centre, Phase I study, healthy adult volunteers (18-50years of age) received single injections of r-hCG 250 ug from reconstituted freeze-dried (1.0mL of 250ug/ml) and liquid (0.5mL of 250ug/0.5ml) formulations in random order, separated by a 10-day wash-out period. Pharmacokinetics (Cmax, AUC, AUClast, tmax and local and systemic tolerability were assessed.Results Pharmacokinetic properties of the two formulations were very similar, with mean Cmax 125mIU/mL (liquid formulation) vs 129mIU/mL (freeze-dried formulation), mean AUC 10350mIU.h/mLvs 10480mIU.h/mL, mean AUClast 10050mIU.h/mLvs10210mIU.h/mL, and median tmax 20 vs 24h. The 90% confidence intervals of the ratios of the treatment means for Cmax, AUC and AUClast all fell within the pre-defined FDA acceptance range of 0.8–1.25, demonstrating the bioequivalence of the two formulations. Both formulations were equally well tolerated; the most frequent adverse events were headache and nausea.Conclusion: The liquid formulation of r-hCG was shown to be bioequivalent to the freeze-dried formulation, with no clinically significant differences in tolerability. The liquid formulation of r-hCG can be expected to provide the same efficacy and tolerability as the freeze-dried formulation when used to trigger final follicular maturation in women undergoing therapies for assisted reproduction, together with a greater convenience of use.