Pharmacokinetic bioequivalence between Nuvaring® (etonogestrel/ethinylestradiol 11.7/2.7 mg) and Ornibel Premium® (etonogestrel/ethinylestradiol 8.25/2.6 mg), a novel polymer composition contraceptive vaginal ring

Objective: This study was a single-centre, randomized, single ring insertion, 2-period, 2-sequence, crossover study design to assess comparative bioavailability and therefore establish bioequivalence of 2 different products of ethinylestradiol/etonogestrel vaginal ring (delivering 0.015/0.12 mg per day) after a single vaginal ring is inserted and worn for 28 days in healthy female subjects. Patients and materials: Forty patients were randomized for this bioequivalence study. The test product contains etonogestrel/ethinylestradiol 8.25/2.6 mg in comparison to etonogestrel/ethinylestradiol 11.00/3.474 mg) of the existing Ornibel® formulation and was compared with Nuvaring® (etonogestrel/ ethinylestradiol 11.7/2.7 mg) (reference product). Results: The results presented herein show that the criteria used to assess bioequivalence between the test and reference products were all fulfilled. 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 ethinyl estradiol and etonogestrel. Conclusions: The test formulation (ethinylestradiol/etonogestrel vaginal ring delivering 0.015 mg/0.12 mg per day, Manufactured by Laboratorios León Farma, S.A.) is judged to be bioequivalent to the Reference formulation (Nuvaring® (ethinylestradiol/etonogestrel) vaginal ring delivering 0.015 mg/0.12 mg dose per day; Manufactured by N.V. Organon) following a single vaginal ring insertion delivering 0.015/0.12 mg dose per day worn for 28 days in healthy adult female subjects. Overall, the drugs tested were generally safe and well tolerated by the subjects included in this study. Clinical trial registry: ISRCTN15148230 with date of 23.09.2025