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...

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Bibliographic Details
Published in:Journal of diabetes investigation 2017-01, Vol.8 (1), p.84-92
Main Authors: Tsuchiya, Saori, Friedman, Evan, Addy, Carol, Wakana, Akira, Tatosian, Daniel, Matsumoto, Yuki, Suzuki, Hideyo, Kauh, Eunkyung
Format: Article
Language:English
Subjects:
Diabetes
Diabetes mellitus
Diabetes mellitus (non-insulin dependent)
Diabetes Mellitus, Type 2 - drug therapy
Dipeptidyl peptidase‐4 inhibitors
Dipeptidyl-peptidase IV
Dipeptidyl-Peptidase IV Inhibitors - administration & dosage
Dipeptidyl-Peptidase IV Inhibitors - adverse effects
Dipeptidyl-Peptidase IV Inhibitors - pharmacokinetics
Dosage
Dose-Response Relationship, Drug
Double-Blind Method
Drug dosages
Heterocyclic Compounds, 2-Ring - administration & dosage
Heterocyclic Compounds, 2-Ring - adverse effects
Heterocyclic Compounds, 2-Ring - pharmacokinetics
Humans
Hypoglycemia
Hypoglycemic Agents - administration & dosage
Hypoglycemic Agents - adverse effects
Hypoglycemic Agents - pharmacokinetics
Japan
Laboratories
Male
Omarigliptin
Once‐weekly
Original
Peptidase
Peptides
Permeability
Pharmacodynamics
Pharmacokinetics
Pyrans - administration & dosage
Pyrans - adverse effects
Pyrans - pharmacokinetics
Tablets
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Summary: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. Omarigliptin is a novel, potent, long‐acting oral dipeptidyl peptidase‐4 (DPP‐4) inhibitor being developed as a once‐weekly (q.w.) treatment for type 2 diabetes (T2DM) patients, with 25 mg and 12.5 mg tablets recently being approved as market formulations in Japan. We evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of omarigliptin in healthy Japanese male subjects after single and multiple dose administration. Omarigliptin was well tolerated and had a pharmacokinetic and DPP‐4 inhibition profile that supports once‐weekly dosing in Japanese patients with T2DM.
ISSN:2040-1116
2040-1124
DOI:10.1111/jdi.12538