title: No clinically relevant drug-drug interactions when dalcetrapib is co-administered with a monophasic oral contraceptive (Microgynon® 30).
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.
  
  
  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.
authors.affiliation: Roche Products Ltd, Welwyn Garden City, UK.
authors.forename: Annie
authors.initials: A
authors.lastname: Young
authors.forename: Judith
authors.initials: J
authors.lastname: Anzures-Cabrera
authors.forename: Michael
authors.initials: M
authors.lastname: Derks
mesh_terms: D000328:Adult; D000577:Amides; D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015415:Biomarkers / Q000097:blood; D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004338:Drug Combinations; D004347:Drug Interactions; D004952:Esters; D004997:Ethinyl Estradiol / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D043373:Follicle Stimulating Hormone, Human / Q000097:blood; D006801:Humans; D016912:Levonorgestrel / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D007986:Luteinizing Hormone / Q000097:blood; D034445:Ovulation Inhibition / Q000187:drug effects*; D011374:Progesterone / Q000097:blood; D013438:Sulfhydryl Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D055815:Young Adult
chemical_list: D000577:Amides; D000924:Anticholesteremic Agents; D015415:Biomarkers; D003277:Contraceptives, Oral, Combined; D004338:Drug Combinations; D004952:Esters; D043373:Follicle Stimulating Hormone, Human; D013438:Sulfhydryl Compounds; C072593:ethinyl estradiol, levonorgestrel drug combination; C411602:dalcetrapib; D004997:Ethinyl Estradiol; D011374:Progesterone; D016912:Levonorgestrel; D007986:Luteinizing Hormone