No clinically relevant drug-drug interactions when dalcetrapib is co-administered with a monophasic oral contraceptive (Microgynon® 30)

Dalcetrapib, a cholesteryl ester transfer protein modulator, under development to increase high-density lipoprotein cholesterol and potentially decrease cardiovascular risk, will potentially be co-prescribed to women on oral contraceptive (OC). Objective: Assess the effect of dalcetrapib on the pharmacokinetics and ability to suppress ovulation of Microgynon (R) 30, a representative monophasic OC. Materials and methods. A single-center, randomized, open-label, two-period crossover study in healthy women receiving monophasic OC. Subjects received Microgynon (R) 30 (ethinylestradiol 0.03 mg/levonorgestrel 0.15 mg) once daily for 21 days followed by 7 treatment-free days (run-in period), then were randomized to Microgynon (R) 30 daily for 21 days with or without dalcetrapib 900 mg daily for Day 1 - 14. Plasma ethinylestradiol and levonorgestrel were measured on Day 14, and luteinizing hormone, follicle stimulating hormone, progesterone and estrogen from Day 11 - 14. The primary endpoint plasma exposure (AUC(0-24) and C-max) on Day 14 was evaluated for ethinylestradiol and levonorgestrel. Safety was monitored throughout. Results: 30 subjects were randomized. The exposure of ethinylestradiol and levonorgestrel was similar when Microgynon (R) 30 was administered with or without dalcetrapib; for ethinylestradiol the geometric mean ratio %, (90% confidence interval (CI)) for AUC(0-24) and C-max were 92 (86 - 98) and 105 (95 - 115) and for levonorgestrel 92 (88 - 96) and 93 (87 - 99), respectively. Concentrations of luteinizing hormone, follicle stimulating hormone, estrogen and progesterone were comparable between treatments. Conclusions: Dalcetrapib has no clinically relevant effect on the pharmacokinetics of ethinylestradiol and levonorgestrel. Contraceptive efficacy of Microgynon (R) 30 is not anticipated to be compromised by co-administration of dalcetrapib.