Since HCV-infected female patients on oral hormonal contraceptives (OC) may be treated
with SOF or SOF/LDV fixed dose combination (FDC), this study evaluated a potential for a drug-drug interaction between SOF or LDV and norgestimate/ethinyl estradiol (NGM/EE, Ortho Tri-Cyclen Lo®), a representative hormonal oral contraceptive (OC). Methods This was an open-label, fixed-sequence, Phase 1 study. Subjects not using NGM/EE were enrolled into Part A (lead-in) and received NGM/EE for 1 menstrual cycle before enrolling into Part B (main study). Subjects on NGM/EE could enroll into Part B directly. In Part B, subjects received CT99021 solubility dmso NGM/EE for 3 sequential cycles. NGM/EE was administered alone (1st cycle), followed by coadministration with SOF for 7 days (Days 8-14; 2nd cycle) or with LDV for 14 days (Days 1-14; 3rd cycle). Safety assessments were conducted throughout the study. NGM, norelgestromin (NGMN; active metabolite), norgestrel (NG; active metabolite), EE, SOF and GS-331007 (predominant circulating nucleoside metabolite of SOF), and LDV were analyzed on Day 14 of each
respective cycle. HTS assay Geometric least squares mean ratios (GLSMR) and 90% confidence intervals (CIs) for AUCtau, Cmax and Ctau were estimated using ANOVA with PK alteration bounds of 70-143%. FSH (Day 14) and LH (Day
14), and progesterone (Day 21) were assessed in all cycles. Results All enrolled subjects (N=15) completed Part B. Study treatments were well tolerated. Nausea and headache were the most frequently reported AEs. All treatment-emergent AEs were mild (Grade 1) or moderate (Grade 2). 上海皓元 Small increases in EE Cmax (∼40%) with LDV or NG AUCtau (∼19%) and Ctau (∼23%) with SOF were noted. No other alterations in NGM/EE PK were observed. SOF, GS-331007 and LDV PK were similar to historical data. FSH, LH and progesterone values were similar in all cycles. Conclusion Coadministration of SOF or LDV with NGM/EE was safe and well tolerated. Based on these results, no loss in contraceptive efficacy is expected upon administration of combined oral contraceptives containing ethinyl estradiol and norgestimate with SOF or SOF/LDV FDC. Accordingly, the use of OC with SOF or SOF/LDV FDC is permitted. Disclosures: Polina German – Employment: GIlead Sciences, Inc; Stock Shareholder: GIlead Sciences, Inc Lisa Moorehead – Employment: Gilead Sciences; Stock Shareholder: Gilead Sciences Phil S. Pang – Employment: Gilead Sciences Anita Mathias – Employment: Gilead Sciences Inc.