title: Effects of Age, Sex, and Obesity on the Single-Dose Pharmacokinetics of Omarigliptin in Healthy Subjects.
abstract: Omarigliptin is being developed as a potent, once-weekly, oral dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes. This double-blind, randomized, placebo-controlled study evaluated the effects of age, sex, and obesity on the pharmacokinetics of omarigliptin in healthy subjects. A single oral dose of omarigliptin 10 mg (n = 6/panel) or placebo (n = 2/panel) was administered in the fasted state to elderly nonobese men and women, young obese (30 ≤ body mass index [BMI] ≤ 35 kg/m(2) ) men and women, and young nonobese women of nonchildbearing potential. Plasma was collected at selected postdose times for evaluation of omarigliptin concentrations. Pharmacokinetic parameters were compared with historical data from a previously-conducted single-dose study in young, healthy, nonobese men. There were no clinically significant differences in omarigliptin AUC0-∞ , the primary pharmacokinetic parameter for assessing efficacy and safety, based on age, sex, or BMI (pooled nonobese elderly versus pooled nonobese young, young nonobese female versus young nonobese male, and pooled young obese versus pooled young nonobese). There were no serious adverse events or hypoglycemic events attributable to omarigliptin administration. Demographic factors and BMI had no meaningful effect on omarigliptin pharmacokinetics, suggesting that dose adjustment based on age, sex, or obesity is not required.
authors.affiliation: Merck & Co., Inc, Kenilworth, NJ, USA. caddy@hmrboston.com.
authors.forename: Carol
authors.initials: C
authors.lastname: Addy
authors.affiliation: Merck & Co., Inc, Kenilworth, NJ, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Tatosian
authors.affiliation: Merck & Co., Inc, Kenilworth, NJ, USA.
authors.forename: Xiaoli S
authors.initials: XS
authors.lastname: Glasgow
authors.affiliation: Merck & Co., Inc, Kenilworth, NJ, USA.
authors.forename: Isaias Noel
authors.initials: IN
authors.lastname: Gendrano
authors.affiliation: Merck & Co., Inc, Kenilworth, NJ, USA.
authors.forename: Christine McCrary
authors.initials: CM
authors.lastname: Sisk
authors.affiliation: Merck & Co., Inc, Kenilworth, NJ, USA.
authors.forename: Eunkyung A
authors.initials: EA
authors.lastname: Kauh
authors.affiliation: Merck & Co., Inc, Kenilworth, NJ, USA.
authors.forename: S Aubrey
authors.initials: SA
authors.lastname: Stoch
authors.affiliation: Merck & Co., Inc, Kenilworth, NJ, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Wagner
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D015992:Body Mass Index; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004311:Double-Blind Method; D005260:Female; D006574:Heterocyclic Compounds, 2-Ring / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications*; D011714:Pyrans / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012737:Sex Factors; D055815:Young Adult
chemical_list: C587539:2-(2,5-difluorophenyl)-5-(2-(methylsulfonyl)-2,6-dihydropyrrolo(3,4-c)pyrazol-5(4H)-yl)tetrahydro-2H-pyran-3-amine; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006574:Heterocyclic Compounds, 2-Ring; D007004:Hypoglycemic Agents; D011714:Pyrans
keywords: demographic analysis; dipeptidyl peptidase-4 inhibitor; omarigliptin; pharmacokinetics; type 2 diabetes mellitus