Bioequivalence and X-Ray Visibility of a Radiopaque Etonogestrel Implant versus a Non-Radiopaque Implant

The etonogestrel (ENG)-releasing implant is a subdermal progestogen-only contraceptive that provides coverage for up to 3 years. This long-acting hormonal contraceptive has been available in Europe since 1998 and in the US since 2006. To date, localization of non-palpable implants at insertion and before removal has been dependent on ultrasound or magnetic resonance imaging by an experienced clinician. To facilitate localization in rare cases of non-palpable implants using widely available equipment without the need for a specialist, a radiopaque ENG implant has been developed that is detectable by two-dimensional x-ray imaging.

This was a 3-year, randomized, double-blind, parallel-group study carried out in nine international clinical trial centres. Women aged 18–40 years at the time of screening, with menstrual cycles of a usual length of 24–35 days and a body mass index of between ≥18 and ≤29 kg/m² were included. Women were assigned to either the radiopaque or non-radiopaque ENG implant in a 1:1 ratio via a block randomization by centre. Bioequivalence testing was performed based on the peak ENG concentration (C_max), and the area under the curve (AUC) for ENG at 6, 24 and 36 months (AUC_{6 mo}, AUC_{24 mo} and AUC_{36 mo}) after insertion. For this purpose, blood sampling for pharmacokinetic determination was performed prior to insertion and for up to 3 years afterwards. Bioequivalence was defined as the 90% confidence interval (CI) of the ratio radiopaque implant/non-radiopaque implant of the geometric means (GMR) within the acceptance range of 0.80–1.25. x-Ray visibility was assessed by two-dimensional x-ray imaging after insertion and before removal of the implant.

The pharmacokinetic profiles of ENG indicated that the radiopaque and non-radiopaque implants were bioequivalent with respect to the geometric mean of C_max (GMR 1.06; 90% CI 0.91, 1.23), AUC_{6 mo} (GMR 1.00; 90% CI 0.91, 1.10), AUC_{24 mo} (GMR 0.98; 90% CI 0.88, 1.10) and AUC_{36 mo} (GMR 1.00; 90% CI 0.89, 1.11). The radiopaque ENG implant was clearly visible in 50 out of 52 women after insertion and in all 52 women before removal, whereas none of the non-radiopaque implants were visible.

Registered as ClinicalTrials.gov identifier NCT00620464.