Search

Introduction Participant's adherence to use of study product is a major concern in microbicide clinical trials, which can impact on proving product efficacy. In a previously described assay, single-use microbicide applicators exposed to the vagina were tested by spraying the applicator with trypan blue dye, resulting in vaginal mucus staining on inserted applicators. As subjects in our Phase 3 trials return applicators only at quarterly visits, often mixing inserted and not-inserted applicators together in the same bag, cross-contamination could confound results. In addition, trypan blue is carcinogenic and thus potentially hazardous to technicians spraying daily. Methods Applicators that were exposed to the vagina were placed in the same bag as unexposed applicators and shaken daily for up to 4 months. Validation was carried out in three clinical sites in South Africa. Results Trypan blue was replaced with FD&C Blue #1 granular food dye. Cross-contamination did not occur, nor did the length of time affect reaction to dye. In South Africa, the assay was validated with an accuracy of over 95%. Conclusion Applicator assay modifications render the test safe and suitable for use in clinical trials.

In a multicenter 1-year trial of contraceptive vaginal rings (rings) involving 150 women, three dose combinations of the progestin Nestorone (NES) and ethinylestradiol (EE) were compared with respect to effectiveness, safety and acceptability. Mean in vitro drug release rates for the three doses were 150 and 15, 150 and 20 and 200 and 15 microg/day of NES and EE, respectively. Each ring remained in situ for 21 days, removed for 7 days and then reinserted for a total of 13 cycles of use. We studied ring performance with respect to pregnancy and other termination events, adverse events, the extent of ovulation inhibition, serum drug levels and bleeding control. We also assessed the rings' effects on the vagina using a standardized colposcopy procedure. Seventy-two percent of the women completed the 1-year (> or = 350 days) study. In studied cycles, luteal activity (progesterone > or = 10 nmol/L) was noted in 17%, 7% and 12% of subjects with monitored cycles at the 150/15, 150/20 and 200/15 doses, respectively (p = .34). Two pregnancies occurred, both in subjects using the 200/15 microg/day ring. Breakthrough bleeding during ring use averaged about 2 days/year and breakthrough bleeding and spotting averaged about 7 days/year. In the entire trial, only two women discontinued because of bleeding problems. Medical conditions, chiefly vaginal problems, personal reasons and device loss or repeated expulsion were the principal reasons given for study discontinuation. Vaginal and cervical colposcopy, conducted with standardized techniques and standardized interpretations, revealed no elevated event incidence attributable to ring use. Clinical performance and adverse event profiles indicate that each of these 1-year NES/EE rings, used on a 21-day-in and 7-day-out regimen, provided women effective, acceptable and safe long-acting contraception under their own control.

Andrea R. Wallace, Aaron Teitelbaum, Livia Wan, Maria Gloria Mulima, Laura Guichard, Stephanie Skoler, Hlengiwe Vilakazi, Fridda S. Mapula, Jasmine Rossier, Sumen N. Govender, Pekka Lahteenmaki, Robin A. Maguire, David M. Phillips⁎ Population Council, New York, NY 10021, USA Department of Obstetrics and Gynecology, NYU School of Medicine, New York, NY 10016, USA Medical Research Council, Isipingo Center, Isipingo Rail, Isipingo, Durban 4110, South Africa Setshaba Research Center, University of Limpopo/Medunsa Campus, Soshanguve, Gauteng 0152, South Africa Empilisweni Center for Wellness Studies, Uluntu Resource Center, University of Cape Town, NY 108, Gugulethu, Cape Town 7750, South Africa Population Council, Johannesburg Office, Hurlingham 2194, South Africa