Abstract
OBJECTIVE: To determine whether serum human follicle-stimulating hormone (FSH) levels after single subcutaneous dosing of highly purified human menopausal gonadotropins (HP-hMG) in a liquid formulation and a powder formulation are bioequivalent. MATERIALS AND METHODS: This was a randomized, two-way, crossover, single-dose, bioequivalence trial comparing Menopur liquid injected by pre-filled pen, with Menopur powder injected by conventional syringe and needle. The primary endpoints were AUC(t) and C(max) of baseline-adjusted FSH. Pituitary-suppressed, healthy women were administered single subcutaneous injections of 450 IU Menopur liquid (600 IU/0.96 mL) and 450 IU Menopur powder (by 2 subcutaneous injections of 225 IU in 1 mL) in a randomized order. The pharmacokinetic parameters of FSH and human chorionic gonadotropin (hCG) were assessed by non-compartmental methods with adjustment for endogenous pre-dose levels. RESULTS: In total, 76 women were randomized, and 56 completed the trial. The mean FSH and hCG serum concentration-time profiles were comparable between the two HP-hMG formulations. The geometric mean ratios and 90% confidence intervals of FSH for HP-hMG liquid versus HP-hMG powder were 1.12 (1.0562 - 1.1889) for AUC(t) and 1.17 (1.0946 - 1.2490) for C(max), showing that the two formulations were bioequivalent. The incidence and severity of adverse events were similar between the two preparations, and both preparations were well tolerated. CONCLUSION: The 90% CIs for the geometric mean ratios of serum FSH AUC(t) and C(max) were both within 0.8000 - 1.2500, thus the two formulations are bioequivalent.