OBJECTIVE: The bioequivalence and tolerability of freeze-dried and liquid formulations of recombinant human follicle-stimulating hormone (r-hFSH) filled-by-mass were assessed in a crossover, open-label, randomised, single-centre, phase I bioequivalence study. METHODS: Following pituitary down-regulation with the gonadotrophin-releasing hormone agonist goserelin, healthy adult volunteers (18years-45years of age) received single subcutaneous injections of r-hFSH , 300 IU, from freeze-dried and liquid formulations in random order, separated by a 7-day washout period. Blood was obtained over 144 h for pharmacokinetic analysis. MAIN OUTCOME MEASURES: These were peak serum FSH concentrations (Cmax,), time to peak concentration (Tmax) and area under the concentration-time curve from zero to the last measurable concentration (AUCJ), local and systemic tolerability. RESULTS: Of 44 volunteers who underwent down-regulation, 39 (18 men, 21 women) completed the study. Cmax and AUClast were similar with the freeze-dried (mean 9.51 IU/L and 844 IU.h/L, respectively) and liquid (mean 8.99 IU/L and 841 IUh/L, respectively) formulations, whereas T was significantly higher with the liquid formulation (median 12h vs 15h, p = 0.0183). The 90% confidence intervals for the ratio of the treatment means for Cnw and AUC,=, were within the pre-defined bioequivalence range of 0.8-1.25. CONCLUSION: Both formulations were well tolerated with regard to both systemic and local adverse events. The freeze-dried and liquid formulations of r-hFSH are bioequivalent and show no significant differences in tolerability. Thus, the liquid formulation is expected to provide comparable efficacy and tolerability to the freeze-dried formulation in clinical use.
RCT Entities:
OBJECTIVE: The bioequivalence and tolerability of freeze-dried and liquid formulations of recombinant human follicle-stimulating hormone (r-hFSH) filled-by-mass were assessed in a crossover, open-label, randomised, single-centre, phase I bioequivalence study. METHODS: Following pituitary down-regulation with the gonadotrophin-releasing hormone agonist goserelin, healthy adult volunteers (18years-45years of age) received single subcutaneous injections of r-hFSH , 300 IU, from freeze-dried and liquid formulations in random order, separated by a 7-day washout period. Blood was obtained over 144 h for pharmacokinetic analysis. MAIN OUTCOME MEASURES: These were peak serum FSH concentrations (Cmax,), time to peak concentration (Tmax) and area under the concentration-time curve from zero to the last measurable concentration (AUCJ), local and systemic tolerability. RESULTS: Of 44 volunteers who underwent down-regulation, 39 (18 men, 21 women) completed the study. Cmax and AUClast were similar with the freeze-dried (mean 9.51 IU/L and 844 IU.h/L, respectively) and liquid (mean 8.99 IU/L and 841 IUh/L, respectively) formulations, whereas T was significantly higher with the liquid formulation (median 12h vs 15h, p = 0.0183). The 90% confidence intervals for the ratio of the treatment means for Cnw and AUC,=, were within the pre-defined bioequivalence range of 0.8-1.25. CONCLUSION: Both formulations were well tolerated with regard to both systemic and local adverse events. The freeze-dried and liquid formulations of r-hFSH are bioequivalent and show no significant differences in tolerability. Thus, the liquid formulation is expected to provide comparable efficacy and tolerability to the freeze-dried formulation in clinical use.