James A. Simona, Paula M. Castañob, Beatrice A. Chenc, Elizabeth I.O. Garnerd aGeorge Washington University, Women's Health & Research Consultants®, 1850 M Street, NW #450 Washington, DC 20036, USA; bColumbia University Irving Medical Center, 622 West 168th Street, New York, NY 10032, USA; cUniversity of Pittsburgh/Magee-Womens Research Institute, 300 Halket St, Pittsburgh, PA 15213, USA; dAgile Therapeutics, 101 Poor Farm Road, Princeton, NJ 08540, USA. Table 1. Percent of Patches by Worst Adhesion Score Reported in a Cycle and Overall (Overall = Reported by Participant At Least Once During the Trial) Table 3: Percent of Patches by Worst Itching Score Reported in a Cycle and Overall (Overall = Reported by Participant At Least Once During the Trial) Figure 1. Schematic of the AG200-15 Contraceptive Patch (Not an actual patch; Not drawn to scale) • AG200-15 (Twirla®) is a transdermal contraceptive delivery system (TCDS) under investigation as a once-weekly prescription contraceptive patch (Figure 1) AG200-15 delivers daily exposure of levonorgestrel (LNG) and ethinyl estradiol (EE) similar to oral doses of 120 μg LNG and 30 μg EE A 28-day cycle consists of consecutive administration of three 7-day patches followed by 7 days off-treatment SECURE (Study to Evaluate Contraception Use, Reliability, and Effectiveness) was a 1-year, single-arm, open-label, multicenter Phase 3 study of the contraceptive efficacy, safety and tolerability of AG200-15 (ClinicalTrials.gov NCT02158572) • • • • To examine wearability of the AG200-15 patch and the impact of adhesion and itching/irritation with using the patch. Adhesion 0: no skin itching; 1: mild; 2: moderate; 3: severe. • 2031 participants applied at least one patch and were included in the safety analysis Over 13 cycles, investigators reported a worst adhesion score of 0 or 1 at 99.4% of visits. Irritation/Itching • • • Women 18 years or older from the US participated SECURE employed broad enrollment criteria with no restrictions based on body mass index or weight Cycle 1 was excluded from analysis since investigator-reported data for cycle 1 occurred on the day of first patch placement (day of enrollment) Patch-related irritation/itching and patch adhesion were evaluated by the investigator at each study visit and daily by the participants through an electronic diary Itching scores were graded by participants using a 4-point scale: 0 (none), 1 (mild), 2 (moderate), and 3 (severe) Irritation scores were graded by participants and investigators using a 4-point scale: 0 (none), 1 (mild), 2 (moderate), and 3 (severe); for investigators, guidance was given as follows: • Participants and investigators reported adhesion scores in support of favorable patch adhesion • For 13 cycles overall, investigators reported a worst skin irritation score of 0 for 95.8% of each visit 99.4% and 99.3% investigators reported a worst adhesion score of 0 or 1 for cycle 2 and cycle 13 visits, respectively Over 13 cycles, 88.7% of patches were reported by participants to have a worst adhesion score of 0 or 1 (Table 1) o Investigators reported good adhesion scores overall and noted increased adhesion from cycles 2 to 13. Participants reported good adhesion scores and a low percentage of patch detachments o o 96.2% and 94.6% of patches in cycles 2 and 13, respectively, were reported by the investigator to have a worst skin irritation score of 0 • • o • For 13 cycles overall, 82.4% of patches were reported by participants to have a worst skin irritation score of 0 (Table 2) 84.1% and 92.5% of patches in cycles 2 and 13, respectively, were reported by the participant to have a worst score of 0 or 1 5.0% of the cumulative number of patches applied during the trial were reported by the participant to be completely detached o • • Low patch-related itching and irritation scores were reported by both investigators and participants indicating favorable wearability Participant experience plays a role in patch wearability o 79.7% and 86.5% of patches in cycle 2 and 13, respectively, were reported by the participant to have a worst skin irritation score of 0 o • • Over 13 cycles, 64.6% of patches were reported by participants to have a worst skin itching score of 0 (Table 3) • o The percent of patches with adhesion, itching, and irritation scores of 0 increased over the duration of the study, A learning curve for patch application experience and an increased knowledge of patch scoring increased wearability parameters through the study • 1.5% of participants discontinued from the study due to patch detachments 58.0% and 72.7% of patches in cycle 2 and 13, respectively, were reported by the participants to have a worst itching score of 0 1.1% and 0.8% of participants discontinued from the study due to application site irritation and itching respectively o o Figure 2. Five-Point Adhesion Assessment Scale (Not an actual patch; Not drawn to scale) • • • Low discontinuation rates due to itching/irritation or adhesion issues indicates these adverse events were not bothersome enough to cause participants to leave the study Table 2: Percent of Patches by Worst Irritation Score Reported in a Cycle and Overall (Overall = Reported by Participant At Least Once During the Trial) None: No irritation or barely perceptible/spotty erythema Mild: Mild erythema covering most of the application site or the skin immediately surrounding the application site Moderate: Moderate erythema covering most of the application site or the skin immediately surrounding the application site, with or without presence of mild edema Severe (Significant): Severe erythema of the application site or the skin immediately surrounding the application site, with or without edema, vesiculation, bullae and/or ulceration o o JS: Consultant/Advisor: AbbVie, Allergan, AMAG, Amgen, Ascend, Azure, Millendo, Nuelle, Radius, Regeneron, Roivant, Sanofi, Sebela, Sermonix, Shionogi, Symbiotec, TherapeuticsMD, Valeant; Speaker: Novo Nordisk, Shionogi, Valeant; Research Support: AbbVie, Agile, Allergan, Bayer, New England Research Institute, Palatin, Symbio, TherapeuticsMD; Stock Ownership, Sermonix. o o PC: Consultant/Advisor: Bayer, Merck; Research Support: Bayer, Merck. BC: Research support: Medicines 360 and Merck, managed by Magee-Womens Research Institute. Advisory board: Merck. EG: Employee/Stock Ownership: Agile Therapeutics. • Patch adhesion scores were rated by participants and investigators using a 5-point scale from 0 to 4, with language modified as appropriate for participant or investigator users (Figure 2) Adhesion scores of 0 and 1 are combined since 90% of the drug delivering portion of the patch remains attached with these scores. o 0: no skin irritation; 1: mild; 2: moderate; 3: severe. Presented at Women’s Health 2018: Translating Research into Clinical Practice, May 4-6, 2018, in Arlington, VA DISCLOSURES Cycle0123 279.713.45.31.6 381.211.75.31.7 480.712.45.21.7 583.69.94.91.6 683.210.25.11.4 783.910.34.51.3 883.610.34.31.8 984.89.64.41.2 1084.29.25.11.5 1184.29.84.41.6 1285.58.54.51.5 1386.58.83.71.0 Overall82.411.24.91.5 CONCLUSIONS STUDY DESIGN, MATERIAL, & METHODS OBJECTIVES Cycle0123 258.028.810.82.3 362.225.010.42.4 464.423.89.22.6 5 66.8 21.4 667.521.1 9.52.3 9.12.4 767.620.49.62.4 866.920.99.72.4 969.519.08.92.6 1068.419.39.82.5 1170.118.39.52.1 1271.617.58.62.4 13 72.7 17.7 8.1 Overall64.623.39.8 1.6 2.3 Cycle0 or 12, 3, or 44 284.115.98.0 3 87.7 12.3 4 88.9 11.1 589.110.9 5.8 4.7 4.5 6 90.2 9.8 790.99.1 3.9 3.5 892.08.03.5 991.98.12.8 10 90.9 9.1 1192.08.0 3.6 3.1 1291.98.13.1 1392.57.52.4 Overall88.711.35.0 RESULTS INTRODUCTION