OBJECTIVE: To compare the bioavailability and tolerability of liquid and freeze-dried formulations of recombinant human chorionic gonadotrophin (r-hCG). SUBJECTS AND METHODS: In an open-label, randomised, single-centre, Phase I study, healthy adult volunteers (18-50 years of age) received single injections of r-hCG 250 microg from reconstituted freeze-dried (1.0 mL of 250 microg/mL) and liquid (0.5 mL of 250 microg/0.5 mL) formulations in random order, separated by a 10-day wash-out period. Pharmacokinetics (C(max), AUC, AUC(last), t(max)) and local and systemic tolerability were assessed. RESULTS:Pharmacokinetic properties of the two formulations were very similar, with mean C(max) 125 mIU/mL (liquid formulation) vs 129 mIU/mL (freeze-dried formulation), mean AUC 10,350 mIU.h/mL vs 10,480 mIU(.)h/mL, mean AUC(last) 10,050 mIU.h/mL vs 10,210 mIU.h/mL, and median t(max) 20 vs 24h. The 90% confidence intervals of the ratios of the treatment means for C(max), AUC and AUC(last) 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.
RCT Entities:
OBJECTIVE: To compare the bioavailability and tolerability of liquid and freeze-dried formulations of recombinant humanchorionic gonadotrophin (r-hCG). SUBJECTS AND METHODS: In an open-label, randomised, single-centre, Phase I study, healthy adult volunteers (18-50 years of age) received single injections of r-hCG 250 microg from reconstituted freeze-dried (1.0 mL of 250 microg/mL) and liquid (0.5 mL of 250 microg/0.5 mL) formulations in random order, separated by a 10-day wash-out period. Pharmacokinetics (C(max), AUC, AUC(last), t(max)) and local and systemic tolerability were assessed. RESULTS: Pharmacokinetic properties of the two formulations were very similar, with mean C(max) 125 mIU/mL (liquid formulation) vs 129 mIU/mL (freeze-dried formulation), mean AUC 10,350 mIU.h/mL vs 10,480 mIU(.)h/mL, mean AUC(last) 10,050 mIU.h/mL vs 10,210 mIU.h/mL, and median t(max) 20 vs 24h. The 90% confidence intervals of the ratios of the treatment means for C(max), AUC and AUC(last) 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.