Paula M. Castañoa, James A. Simonb, Beatrice A. Chenc, Lisa Floodd, Michelle Previterad, Joseph A. Chiodo IIId, Elizabeth I.O. Garnerd aColumbia University Irving Medical Center, 622 West 168th Street, New York, NY 10032, USA; bGeorge Washington University, Women's Health & Research Consultants®, 1850 M Street, NW #450 Washington, DC 20036; cUniversity of Pittsburgh/Magee-Womens Research Institute, 300 Halket Street, Pittsburgh, PA 15213, USA; dAgile Therapeutics, 101 Poor Farm Road, Princeton, NJ 08540, USA. • The mean age (in years) of naïve users was 24.5 and 27.9 for current users. Further baseline information is presented in Table 2 Safety • AG200-15 (Twirla®) is a transdermal contraceptive delivery system under investigation as a once-weekly prescription contraceptive patch AG200-15 delivers daily exposure of 120 g of levonorgestrel (LNG) and 30 g of ethinyl estradiol (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) • • • • 2031 participants applied at least one patch and were included in the safety analysis o49% of subjects completed the study 1085 (53%) subjects experienced a TEAE (Table 4) 552 (27%) were definitely related, probably related, or possibly related to study drug 224 (11%) subjects discontinued due to an adverse event • 3 naïve users and 6 current users experienced 10 serious adverse events (SAEs) (Table 6) oOne current user experienced 2 SAEs 6 of the 10 SAEs were characterized as unrelated to study drug Table 1: Subject Disposition • • • Table 6. Serious Adverse Events • Table 4. Safety Evaluation • To evaluate the safety of the AG200-15 patch in women with a range of experience with hormonal contraception. related • SECURE employed broad enrollment criteria with no restrictions on body mass index or weight Subjects were 18 years of age, sexually active, and with menses every 21-38 days All study sites were in the U.S. Safety was evaluated for women who were: oCurrent (actively using a hormonal contraceptive at study entry) users of hormonal contraception oNaïve (had never used any hormonal contraceptive) users of hormonal contraception Treatment-emergent adverse events (TEAEs) were evaluated and defined as adverse events that occurred from start of treatment to the day after the last patch was removed Hormone-related adverse reactions were evaluated and defined as reactions likely caused by combination hormonal contraception *Drug-related: definitely related, probably related, or possibly related. Table 2. Baseline Population Characteristics • • For naïve users (Table 5): 81 (43%) reported TEAEs 16 (8%) reported TEAEs resulting in study drug discontinuation 3 (2%) reported SAEs 2 (1%) reported SAEs resulting in study drug discontinuation o o o o • • *Ectopic Pregnancy was classified as occurring on treatment • For current users: 431 (61%) reported TEAEs 92 (13%) reported TEAEs resulting in study drug discontinuation 6 (0.9%) reported SAEs 3 (0.4%) reported SAEs resulting in study drug discontinuation Summary of TEAEs o o o o Table 5. • Overall, the safety profile for AG200-15 is comparable to recently approved combined hormonal contraceptives1 Higher percentages of any TEAEs and TEAEs resulting in study drug discontinuation were reported among women who were current users compared to naïve users. Knowledge of the contraceptive history of women seeking hormonal contraception may help prescribers focus their counseling. Hormone-related adverse events were similar between naïve and current users. • • • • • • • Of current users, 551 (78%) had never used transdermal contraceptives The most widely used current hormonal contraceptive method was oral contraceptive pills (33%) (Table 3) The most used method overall was the male condom with or without spermicide (57%) • 1 Grossman Barr N. Managing Adverse Effects of Hormonal Contraceptives. Am Fam Physicians. 2010;82(12):1499-1596. Figure 1. Schematic of the AG200-15 Contraceptive Patch (Not an actual patch; Not drawn to scale) Table 3. Summary of Current Contraceptive Methods PC: Consultant/Advisor: Bayer, Merck; Research Support: Bayer, Merck. 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. BC: Research support: Medicines 360 and Merck, managed by Magee-Womens Research Institute. Advisory board: Merck. LF: Former employee of Agile Therapeutics. MP: Former Consultant/Advisor: Agile Therapeutics. JC/EG: Employee/Stock Ownership: Agile Therapeutics. *Drug-related: definitely related, probably related, or possibly related. • Hormone-related adverse events reported by at least 2% of naïve users were headache (n=8, 4.2%), nausea (n=6, 3.2%), dysmenorrhea (n=5, 2.6%), mood swings (n=4, 2.1%), and acne (n=3, 1.6%) For current users, hormone-related adverse reactions reported by at least 2% were nausea (n=27, 3.8%), headache (n= 23, 3.3%), dysmenorrhea (n=21, 3.0%), acne (n=16, 2.3%), and mood swings (n=8, 1.1%) • Subject Disposition and Characteristics • • 190 naïve users were enrolled in the study and 78 (41%) completed the study (Table 1) 704 current users were enrolled and 403 (57%) completed the study Former and recent users are not presented *Two subjects reported both patch and oral • Presented at American Society for Reproductive Medicine 2018 Scientific Congress & Expo October 6-10, 2018, in Denver, CO Current Contraceptive MethodUsers n (%) Oral*604 (33) Patch*41 (2) Vaginal Ring61 (3) Injectable1 (0.1) Male Condom with or without Spermicide1050 (57) Female Condom with or without Spermicide12 (0.7) Diaphragm, Cervical Cap, or Sponge with or without6 (0.3) Spermicide Rhythm Method (Fertility Awareness), Withdrawal, or314 (17) Outercourse Emergency Contraception1 (0.1) Other4 (0.2) DISCLOSURES RESULTS REFERENCES ParameterNaïve Users (%,Current Users (%, n=190)n=704) TEAEs81 (43)431 (61) Study-Related* TEAEs45 (24)221 (31) Severe TEAEs6 (3)31 (4) Serious TEAEs (SAE)3 (2)6 (0.9) (including death) Drug-Related* Serious1 (0.5)3 (0.4) TEAEs (SAE) TEAEs Resulting in16 (8)92 (13) Study Drug Discontinuation TEAEs Resulting in00 Death CONCLUSIONS ParameterNaïve Users (n=190)Current Users (n=704) Age, mean (SD)24.5 years (5.7)27.9 years (6.2) Weight, median (range)73.9 kg (39.5-147.0)73.8 kg (39.0-144.7) BMI, median (range)27.5 kg/m2 (16.7-50.7)27.4 kg/m2 (15.1-51.5) BMI 30 kg/m2(obese), %3329 Black/ African3116 American, % White, %5675 Hispanic/ Latino, %2818 STUDY DESIGN, MATERIAL, & METHODS OBJECTIVE Serious Adverse EventUser StatusStudy Drug Relationship AppendectomyNaïveUnrelated Suicide AttemptNaïvePossibly related Ectopic Pregnancy*NaïveUnrelated Bipolar DisorderCurrentUnrelated Seizure/Recurrent SeizureCurrentUnrelated/Possibly Deep Vein ThrombosisCurrentUnrelated CholelithiasisCurrentPossibly Related AppendicitisCurrentUnrelated Pulmonary EmbolismCurrentProbably related CategoryAG200-15 (%, N=2031) Subjects with Any TEAEs1085 (53) Subjects with Any Study Drug-Related* TEAEs552 (27) Subjects with Severe TEAEs92 (5) Subjects with Serious TEAEs (SAE)40 (2) Subjects with Study Drug-Related* Serious TEAEs15 (0.7) (SAE) Subjects with TEAEs Resulting in Study Drug224 (11) Discontinuation Subjects with TEAEs Resulting in Death0 Disposition StatusNaïve UsersCurrent (%)Users (%) Enrolled190704 Safety190704 Completer78 (41)403 (57) Reason for Discontinuation Any Reason112 (59)301 (43) Adverse Event13 (7)93 (13) Death00 Non-Compliance22 (12)26 (4) Lost to Follow Up33 (17)48 (7) Subject Decision29 (15)92 (13) Pregnancy7 (4)15 (2) INTRODUCTION
