PII-046

C. Loghin, A. de la Peña, X. Cui; Eli Lilly and Company, Indianapolis, IN

BACKGROUND: Dulaglutide is a once weekly long-acting glucagon-like peptide 1 agonist developed to improve glycemic control in adults with type 2 diabetes. Dulaglutide slows gastric emptying (GE); this effect is largest after the first dose and diminishes with subsequent doses. This study assessed the effect of a single subcutaneous dulaglutide 1.5 mg dose on the pharmacokinetics (PK) of a combination contraceptive: Ortho-Cyclen® (OC) in healthy female subjects.
METHODS: The open-label, fixed-sequence study first had a 28-day lead-in period. Subjects (22 entered/15 completers) then received 28 days of OC alone (Period 1), and an additional 28 days of OC (Period 2), with a single dose of dulaglutide 1.5 mg coadministered on Day 19. OC packs included 21 norgestimate (NGM) and ethinyl estradiol (EE) tablets, and 7 non-active tablets. Steady-state concentrations of EE and norelgestromin (NGMN, active metabolite of NGM) are reached by Days 7 and 21, respectively; NGMN and EE PK was assessed by non-compartmental analysis on Day 21 of both periods.
RESULTS: Dulaglutide did not affect the overall exposure to EE or NGMN; statistically significant mean (90% CI) maximum concentration (Cmax) reductions were ~26% (16-35%) for NGMN and ~13% (3-21%) for EE; and time to Cmax delays were 2 hours and 0.30 hours for NGMN and EE, respectively. These data are consistent with the GE delay of dulaglutide and the known large PK variability of OC. Reductions in Cmax of up to 40% are common in OC food‑effect studies, however, OCs are taken independently of food. The dulaglutide and OC coadministration was generally tolerated, with gastrointestinal related disorders most commonly reported.
CONCLUSION: Based on PK, safety, and tolerability data, OC and dulaglutide may be administered concomitantly without dose adjustment.