Pharmacokinetic bioequivalence between (etonogestrel/ethinylestradiol 11.7/2.7 mg) NuvaRing ® and ornibel premium ® (etonogestrel/ethinylestradiol 8.25/2.6 mg), a novel polymer composition contraceptive vaginal ring

Abstract

Objective This was a single-centre, randomised, single-ring insertion, 2-period, 2-sequence, crossover study designed to assess comparative bioavailability and thereby establish bioequivalence of two ethinylestradiol/etonogestrel vaginal rings (delivering 0.015/0.12 mg per day) after a single vaginal ring was inserted and worn for 28 days in healthy female subjects.Patients and materials Forty subjects were randomised for this bioequivalence study. The test product contains etonogestrel/ethinylestradiol 8.25/2.6 mg, compared with etonogestrel/ethinylestradiol 11.00/3.474 mg in the existing Ornibel® formulation, and was compared with NuvaRing (etonogestrel/ethinylestradiol 11.7/2.7 mg) as the reference product.Results The criteria for bioequivalence between the test and reference products were met. The test-to-reference ratio of geometric LSmeans and corresponding 90% CI for Cmax after Day 1, C504, AUC0-504, C672 and AUC0-672 were all within the acceptance range of 80.00 to 125.00% for ethinylestradiol and etonogestrel. The percentage reduction in residual hormone content remaining in the device after 21 days use, in comparison with NuvaRing®, is as follows: ETO residue after 21 days was reduced by 30%, and EE residue after 21 days was reduced by 4%.Conclusions The test formulation (ethinylestradiol/etonogestrel vaginal ring delivering 0.015/0.12 mg per day; manufactured by Laboratorios Leon Farma, S.A.) is bioequivalent to the reference formulation (NuvaRing®; manufactured by N.V. Organon) following a single vaginal ring insertion worn for 28 days in healthy adult female subjects. Overall, the products tested were generally safe and well tolerated.