Effects of Multiple Doses of Albiglutide on the Pharmacokinetics, Pharmacodynamics, and Safety of Digoxin, Warfarin, or a Low-Dose Oral Contraceptive

Abstract

Aims: Albiglutide is a glucagon–like peptide–1 analog that is currently under investigation for the treatment of type 2 diabetes mellitus as a once–weekly injection. Three open–label phase 1 studies were conducted in healthy human participants to investigate potential pharmacokinetic (PK) and/or pharmacodynamic (PD) interactions between albiglutide and medications that may be used concomitantly. Methods: Digoxin 0.5 mg, warfarin 25 mg, or a standard, low–dose oral contraceptive containing norethindrone (NE) 0.5 mg and ethinyl estradiol (EE) 0.035 mg were administered alone and after steady–state albiglutide exposure (50 mg weekly for 4–5 weeks). The lack of a drug–drug interaction was concluded if the 90% CIs of geometric least–squares means ratio of area under the curve and maximum concentration were fully contained within 0.80 to 1.25. The effects of albiglutide on the PD of warfarin (international normalized ratio) and on the PD of a low–dose oral contraceptive (luteinizing hormone [LH], follicle–stimulating hormone [FSH], and progesterone) were assessed. Safety and tolerability were also assessed. Results: Overall, the PK profiles of digoxin, warfarin, NE, and EE were unaffected by albiglutide administration; standard bioequivalence criteria were met with a few exceptions that were not considered clinically relevant. Warfarin international normalized ratio was unaffected by albiglutide administration. No clinically meaningful differences in LH, FSH, or progesterone were observed. Most treatment–emergent adverse events were mild, and all resolved by study end. Conclusion: Based on tolerability and the lack of clinically significant PK or PD interactions, no dose adjustments should be required when albiglutide is administered concomitantly with these medications.