Segesterone acetate/ethinyl estradiol 12-month contraceptive vaginal system safety evaluation

Abstract Objectives To evaluate safety outcomes from clinical studies of a 12-month contraceptive vaginal system (CVS) releasing an average of segesterone acetate (SA) 150 mcg and ethinyl estradiol (EE) 13 mcg daily. Study design We integrated clinical safety data from nine studies in which women used the CVS for 21 consecutive days and removed it for 7 days of each 28-day cycle. Four studies used the final manufactured CVS, including a 1-year pharmacokinetic study, two 1-year phase 3 trials and a second-year treatment extension study. We assessed safety by evaluating adverse events women reported in a daily diary. We also included data from focused safety studies evaluating endometrial biopsies, vaginal microbiology and liver proteins from one of the phase 3 studies. Results The combined studies included 3052 women; 2308 women [mean age 26.7±5.1 years; mean body mass index (BMI) 24.1±3.7 kg/m 2 ] received the final manufactured CVS, of whom 999 (43.3%) completed 13 cycles of use. Women using the final CVS most commonly reported adverse events of headache ( n =601, 26%), nausea ( n =420, 18%), vaginal discharge/vulvovaginal mycotic infection ( n =242, 10%) and abdominal pain ( n =225, 10%). Few ( n =1); BMI>29 kg/m 2 ( n =2)]. During 21,482 treatment cycles in the phase 3 studies evaluable for expulsion, women reported partial expulsions in 4259 (19.5%) cycles and complete expulsions in 1509 (7%) cycles, most frequently in the initial cycle [499/2050 (24.3%) and 190/2050 (9.3%), respectively]. Safety-focused studies revealed no safety concerns. Conclusion The 1-year SA/EE CVS has an acceptable safety profile. Additional studies are warranted in obese women at higher risk of VTE. Implications This 1-year contraceptive vaginal system represents a new long-term, user-controlled and procedure-free option with a safety profile similar to other combination hormonal contraceptives. The same precautions currently used for combination hormonal contraceptive prescriptions apply to this new contraceptive vaginal system.