Bioequivalence of liquid and freeze-dried recombinant human follicle-stimulating hormone

Bioequivalence of liquid and freeze-dried recombinant human follicle-stimulating hormone
January 2005
Lugan I.1; Febbraro S.2; Lecuelle H.1; Papasouliotis O.1; Ho-Nguyen Q.1; Buraglio M.1
1: Serono International SA, R&Ph Development HPG, Geneva, Switzerland
2: SIMBEC Research Ltd, Merthyr Tydfil, Mid Glamorgan, UK
Current Medical Research and Opinion, January 2005, vol. 21, no. 1, pp. 121-125(5)
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Abstract:
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 (18 years?45 years 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 (AUClast), 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 IU?h/L, respectively) formulations, whereas Tmax was significantly higher with the liquid formulation (median 12 h vs 15 h, p = 0.0183). The 90% confidence intervals for the ratio of the treatment means for Cmax and AUClast 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.