Single and multiple dose pharmacokinetics and pharmacodynamics of omarigliptin, a novel, once‐weekly dipeptidyl peptidase‐4 inhibitor, in healthy Japanese men

Aims/Introduction: Omarigliptin is a novel, potent, long-acting oral dipeptidyl peptidase-4 inhibitor being developed as a once-weekly (q.w.) treatment for type 2 diabetes mellitus patients, with 25 mg and 12.5 mg tablets recently being approved as market formulations in Japan. Materials and Methods: This was a two-part, double-blind, randomized, placebo-controlled study in healthy Japanese men to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of omarigliptin after single dose (5-100 mg) and multiple dose (1-50 mg q.w. for 3 weeks) administration. Results: Omarigliptin was rapidly absorbed with a time to maximum concentration of 0.5-4 h. The pharmacokinetic profile was biphasic with a long terminal half-life > 100 h. The area under the concentration-time curve from 0 to 168 h, maximum concentration and the concentration at 168 h post-dose increased dose-dependently after 3 weeks of once-weekly dosing for doses ranging 1-50 mg, with accumulation ratios ranging 1.03-1.35 and 0.87-1.36 for the area under the concentration-time curve from 0 to 168 h and maximum concentration, respectively. Plasma dipeptidyl peptidase-4 inhibition levels 1 week post-dose increased with dose, ranging 79.2-94.0% after 5-100 mg single dose administration and 51.3-90.2% after 1-50 mg multiple once-weekly dose administration. Administration with food did not meaningfully alter the pharmacokinetics of omarigliptin. Omarigliptin was generally well tolerated, with no hypoglycemia being reported. Conclusion: The results of the present study in healthy Japanese men showed that omarigliptin was well tolerated and had a pharmacokinetic and dipeptidyl peptidase-4 inhibition profile that supports once-weekly dosing in Japanese patients with type 2 diabetes mellitus.