A prospective, open-label, multicenter study to assess the pharmacodynamics and safety of repeated use of 30 mg ulipristal acetate.

ABSTRACT

OBJECTIVE: Ulipristal acetate (UPA) 30 mg is safe and effective for emergency contraception (EC). This prospective open-label exploratory study was conducted to obtain additional data on the pharmacodynamic effects of repeated dose of UPA 30 mg during an 8-week period (effects on ovulation inhibition, hormonal levels, endometrium and cervical mucus). Safety and tolerability data of repeated use of UPA EC were also collected. STUDY DESIGN: A total of 23 healthy female, healthy sterilized women participated in two substudies receiving UPA for 8 consecutive weeks. In substudy 1, UPA 30 mg was administered every 7 days (Q7D n=12); while in substudy 2, every 5 days (Q5D n=11). Subjects were monitored three times a week in a baseline cycle and during treatment with transvaginal ultrasounds, hormonal measurements and cervical mucus evaluation. Laboratory safety measurements and standard surrogate thrombosis risk markers were measured at baseline and within a few days of the last tablet. A luteal phase endometrial biopsy was taken in the baseline cycle and posttreatment. RESULTS: A total of 11/12 (91.7%) and 8/11 (72.7%) of the subjects ovulated at least once in substudy Q7D and Q5D, respectively, with similar, normal hormonal profiles. No effect on cervical mucus was observed. All biopsies were classified as benign in both substudies; 5/11 biopsies on Q5D posttreatment were classified as nonphysiological with some of typical progesterone receptor modulator-associated endometrial changes. UPA was well tolerated in both treatment arms while clinical laboratory results and surrogate thrombosis markers were reassuring. CONCLUSIONS: Repeat use of 30 mg oral UPA every 5 or 7 days for 8 weeks initially delays follicular rupture but ovulation eventually occurs with time in most subjects. Safety data indicate that UPA 30 mg could be safely administered if needed more than once for EC in a given menstrual cycle. IMPLICATIONS These data demonstrate that repeated use of UPA 30 mg is safe. However, ovulation eventually occurs in a high proportion of women in spite of repeated treatments in both studied regimens. Nevertheless, since the stage of follicular development of women seeking initial or repeat EC use is generally unknown, the repeated use of UPA may still delay follicular rupture and prevent an unintended pregnancy in the event of further unprotected intercourse.