Contraception in Female Volunteer in Alzheimer’s Prevention Initiative Autosomal‐dominant Alzheimer’s disease Colombia Trial, a Phase II Clinical Trial to Test Safety and Efficacy of Crenezumab

Background In most prevention clinical trials contraceptive use is required. The API ADAD Colombia Trial was a phase II, double‐blind, placebo‐controlled clinical trial to evaluate the safety and efficacy of the investigational product crenezumab. Trial period A was carried out from 2013 to 2021, during which 252 cognitively unimpaired PSEN1 E280A mutation carriers and non‐carriers were enrolled to be treated with crenezumab or placebo, including 159 women from 30 to 60 years of age. We describe strategies to address contraception in female volunteers. Method For women of childbearing age, using two contraceptive methods and taking a pregnancy test before each administration of the investigational product was required. Different strategies were used to try to guarantee the adherence of the participants to the contraception methods: comprehensive educational activities, educational brochures, annual newsletters, medical advice on contraception methods and in some cases referral to a gynecology specialist to select the best contraception method. The General Fertility Rate (GFR) was used to evaluate the efficacy of the implemented strategies for contraceptive use. Using the parametric Welch’s t‐test, we compared the GFR rates between trial volunteers and the Colombian population using data reported by the National Administrative Department of Statistics. Result Tubectomy plus condom use 33.9% (54/159) and oral contraceptives plus condom use 15.1% (24/159) were the most common combinations used by volunteers. Ten women (6.3%) became pregnant during trial period A. Four of these pregnancies were due to therapeutic failure because at each visit the use of contraceptive methods was controlled and recorded in the medical history, three due to inappropriate contraceptive drug use reported by the participants, two were planned by the volunteers and one participant with difficulties in adherence to follow up visits. Significantly lower mean of GFR (p‐value = 2.68×10‐5) was observed in API ADAD volunteers compared to the Colombian population over the 7 years. Conclusion According the p‐value obtained to compare the GFR between trial volunteers and the Colombian population, the strategies used to address contraception by the site were effective for the prevention of pregnancies.