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

<jats:title>Abstract</jats:title><jats:sec><jats:title>Aims/Introduction</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Materials and Methods</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>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.</jats:p></jats:sec>