Objective: Evaluate bioequivalence, based on norelgestromin (NGMN) and ethinyl estradiol (EE) plasma concentrations, and adhesion of a transdermal contraceptive patch containing a newly sourced adhesive component (test) at end of shelf life (EOSL) vs. the marketed EVRA patch (reference) at beginning of shelf life (BOSL).
Materials and methods: In this randomized, double-blind, two-way crossover study, healthy women received a single, 7-day application of test and reference patches in 4 sequences: two 11-day treatment periods separated by a 21-day washout. Assessments included NGMN and EE pharmacokinetics (PK), adhesion (per European Medicines Agency (EMA) 5-point scale), irritation potential and application-site reactions, and tolerability. Patches were bioequivalent if 90% CIs of geometric mean ratios (GMRs) of test/reference for Cmax, AUC168h, AUC0-tlast, and AUC∞ were 80 - 125%. Patch adhesion was comparable if ratios of geometric mean cumulative adhesion percentages were ≥ 90%.
Results: 68 women were randomized, and 62 completed both treatments. 55 and 59 participants in the reference and test group, respectively, had patch adhesion ≥ 80% (EMA score 0 - 1) at end of treatment. Bioequivalence was demonstrated: GMRs for pharmacokinetic (PK) parameters ranged from 102.76 - 105.57% for NGMN and 93.78 - 94.80% for EE, and associated 90% CIs were fully within the bioequivalence acceptance range (80 - 125%) for both. The patches had comparable adhesion properties (GMR, 101.4% (90% CI: 99.2 - 103.6)) and incidences of treatment-emergent adverse events.
Conclusion: NGMN-EE transdermal test patch at EOSL was bioequivalent to the marketed patch at BOSL, supporting widening the product's shelf-life specification. Adhesive properties and safety profiles were comparable between patches.