Pharmacokinetic bioequivalence, safety and acceptability of Ornibel®, a new polymer composition contraceptive vaginal ring (etonogestrel/ethinyl estradiol 11.00/3.474 mg) compared with Nuvaring® (etonogestrel /ethinylestradiol 11.7/2.7 mg)

Objective: To show the clinical development of Ornibel (R) (ExeltisHealthcare, Spain) a contraceptive vaginal ring manufactured with a new polymer composition and containing etonogestrel/ethinylestradiol, compared to Nuvaring (R) (MSD, Spain). Subjects and methods: Randomised, single dose, 2-period, 2-sequence, 2-stage crossover, comparative bioavailability study conducted in 40 healthy female subjects. All subjects received both treatments for 28 days in each of two periods, separated by a 28 days washout. Ornibel (R) contains etonogestrel/ethinylestradiol 11.00/3.47mg and Nuvaring (R) contains etonogestrel/ethinylestradiol 11.7/2.7 mg, both rings delivering 120/15 mu g/day. For the calculation of pharmacokinetic parameters, 37 blood samples were collected up to 840 h after each ring insertion to quantify plasma concentrations of etonogestrel and ethinylestradiol using a validated MS/MS-HPLC. Safety was assessed by adverse events recording, clinical laboratory and vital signs and tolerability by vaginal examination. Acceptability was investigated by a 5-point scale questionnaire. Results: Bioequivalence was demonstrated in the first stage as the 94.12% Confidence Intervals of the primary parameters laid within the 80-125% acceptance range for both etonogestrel (C-max: 96.81-112.20%; AUC(0-504h): 98.71-108.61%; AUC(0-t): 100.14-109.10%) and ethinylestradiol. (C-max: 105.91-120.62%; AUC(0-504h): 105.47-114.59%; AUC(0-t): 108.31-117.61%). During the first day of use a burst effect was observed with Nuvaring (R), with significantly higher level of ethinylestradiol (Cmax0-24h ratio: 78.34%, 94.12CI: 73.55-83.45%). Both products were well tolerated and accepted, without significant differences between them. Conclusion: Ornibel (R) is bioequivalent to Nuvaring (R) in terms of efficacy, safety, tolerability and acceptability. The new polymer composition provides Ornibel (R) with more stability and gradual hormonal release during the first day of use, particularly for ethinylestradiol.