Phase I, two-way, crossover study to demonstrate bioequivalence and to compare safety and tolerability of single-dose XM17 vs Gonal-f(®) in healthy women after follicle-stimulating hormone downregulation

BACKGROUND: XM17 is a recombinant human follicle-stimulating hormone (rhFSH) intended mainly for use in controlled ovarian hyperstimulation and the treatment of anovulation. The purpose of the current study was to establish bioequivalence, safety and tolerability of single 300-IU subcutaneous (sc) doses of XM17 to that of the reference follitropin alfa (Gonal-f(®)) in healthy young women. METHODS: This open-label, Phase I, single-dose, single-center, two-way crossover study was conducted from February to May 2009. Thirty-six women aged 18–39 years were included, with a study duration of ~27 days per participant. After endogenous FSH downregulation with goserelin (3.6 mg) on study Day 0, XM17 and Gonal-f(®) were administered on Days 11 and 19 in random sequence. Frequent serum samples were drawn for standard pharmacokinetics until 168 h postdosing. Laboratory values, adverse events (AEs) and local tolerability were assessed throughout the study period. Primary endpoints included C(max) and AUC(0-t). Secondary endpoints included additional pharmacokinetic (PK) parameters, safety and tolerability. RESULTS: Ratios of XM17 to Gonal-f(®) for C(max) and AUC(0-t) equaled 1.017 (90 % confidence interval [CI]: 0.958, 1.080) and 1.028 (90 % CI: 0.931, 1.134), respectively, with the CIs contained within the predefined interval (0.8, 1.25). Ratios for AUC(0-168h), AUC(0-∞) and t(1/2) were also ~1, and no difference in t(max) was detected. Both XM17 and Gonal-f(®) were well tolerated, with no detectable anti-FSH antibodies, serious AEs or AEs leading to discontinuation or dose reduction. CONCLUSIONS: PK bioequivalence of single 300-IU sc doses of XM17 to the reference product Gonal-f(®) was statistically demonstrated. XM17 was well tolerated both systemically and locally. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02592031; date of registration: 28 October, 2015.