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

Abstract

Objective: To show the clinical development of Ornibel^® (ExeltisHealthcare, Spain) a contraceptive vaginal ring manufactured with a new polymer composition and containing etonogestrel/ethinylestradiol, compared to Nuvaring^® (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^® contains etonogestrel/ethinylestradiol 11.00/3.47 mg and Nuvaring^® contains etonogestrel/ethinylestradiol 11.7/2.7 mg, both rings delivering 120/15 µg/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^®, with significantly higher level of ethinylestradiol (C_max0-24h ratio: 78.34%, 94.12CI: 73.55-83.45%). Both products were well tolerated and accepted, without significant differences between them.

Conclusion: Ornibel^® is bioequivalent to Nuvaring^® in terms of efficacy, safety, tolerability and acceptability. The new polymer composition provides Ornibel^® with more stability and gradual hormonal release during the first day of use, particularly for ethinylestradiol.

Keywords: Etonogestrel; acceptability; burst effect; comparative bioavailability; contraceptive vaginal ring; ethinylestradiol; user satisfaction.