Proof-of concept, randomized 3-month study to evaluate the effects of 3 contraceptive intrauterine systems delivering copper and a daily dose (5,20 or 40mcg) of Ulipristal acetate ovulation, endometrial changes and bleeding patterns in normally cycling women

• Grant number: 15/25614-7
• Support Opportunities: Scholarships abroad - Research
• Effective date (Start): August 15, 2016
• Effective date (End): August 14, 2017
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Carolina Sales Vieira
• Grantee: Carolina Sales Vieira
• Host Investigator: Regine Sitruk Ware
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Research place: Population Council, United States

Abstract

Objective: this study has the objective to determine pharmacodynamic (PD) effects of an intrauterine system (IUS) delivering copper (Cu)(200mm2) and either 5, 20 or 40 mcg of ulipristal (UPA) per day during 12 weeks of continuous treatment on bleeding patterns, Progesterone Receptor Modulator Associated Endometrial Changes (PAEC) incidence in the endometrium, follicular function and ovulation and to assess systemic absorption and PK effects of UPA delivered by a Cu (200 mm2) IUS in combination with UPA delivered at a rate of 5, 20 or 40 µg/day during 12 weeks of use. Methods: this is a proof-of-concept study utilizing a randomized dose-finding, parallel design to assess the effects of an IUS delivering Cu and 5, 20, or 40 mcg of UPA over 12 weeks (Phase I Study)This study will include approximately 30 women (10 per group) at one study site. Each woman will be in the trial for approximately 6 months, which is equivalent to 6 cycles. The first cycle will be a baseline cycle. There will be 3 cycles in the active treatment portion of the study followed by 2 post treatment cycles. Daily diaries will be used to record vaginal bleeding, spotting or amenorrhea, and any evidence of IUD expulsion. Pharmacodynamic effects will be evaluated for each treatment group by determining follicular function and, whether ovulation occurs, as determined by transvaginal ultrasound (TVU) assessments and serum estradiol and progesterone levels. Plasma UPA levels at specified time points will be measured and described. Endometrial safety will be assessed by endometrial thickness (ET) measurements in all ultrasound evaluations performed twice a week during the 12 weeks of use and also during the recovery cycle once a week. Endometrial biopsies will also be conducted to assess endometrial changes suggestive of proliferation or other changes previously described as PAECs. Both pathological examination and proliferation markers will be assessed before, during and following treatment. (AU)