No clinically relevant drug–drug interactions when dalcetrapib is co-administered with a monophasic oral contraceptive (Microgynon® 30)
Annie Young1, Judith Anzures-Cabrera1, Michael Derks2
1 Roche Products Ltd, Welwyn Garden City, UK, and 2 F. Hoffmann-La Roche Ltd, Basel, Switzerland
DOI 10.5414/CP201647
Abstract
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® 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® 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® 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 (AUC0–24 and Cmax) 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® 30 was administered with or without dalcetrapib; for ethinylestradiol the geometric mean ratio %, (90% confidence interval (CI)) for AUC0–24 and Cmax 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® 30 is not anticipated to be compromised by co-administration of dalcetrapib.
Author Details
Authors
Departments
- 1 Roche Products Ltd, Welwyn Garden City, UK, and
- 2 F. Hoffmann-La Roche Ltd, Basel, Switzerland
Address
Michael Derks, MD
F. Hoffmann-La Roche Ltd
Bldg. 663, Office 2139
4070, Basel, Switzerland
Email:
[email protected]
Citation
Annie Young, Judith Anzures-Cabrera and Michael Derks.No clinically relevant drug–drug interactions when dalcetrapib is co-administered with a monophasic oral contraceptive (Microgynon® 30). 2012; 50: 248-256. doi: 10.5414/CP201647.
