title: Safety, tolerability, pharmacokinetics, and pharmacodynamics of exenatide once weekly in Japanese patients with type 2 diabetes.
abstract: This randomized, placebo-controlled, double-blind, parallel study assessed the safety, tolerability, pharmacokinetics, and pharmacodynamics of exenatide once weekly (QW) in 30 Japanese patients with type 2 diabetes (T2D) suboptimally controlled by diet and exercise alone or combined with biguanide, sulfonylurea, thiazolidinedione, or combinations of these agents (58.6% male; 58+/-9 years; body mass index 26.3+/-2.9 kg/m(2); hemoglobin A(1c) [HbA(1c)] 7.4+/-0.8%; fasting plasma glucose [FPG] 156.1+/-29.1 mg/dL; duration of T2D 6+/-5 years; means +/- SD). Patients were randomized in a 1:1:1 ratio to subcutaneous placebo QW, exenatide QW 0.8 mg, or exenatide QW 2.0 mg for 10 weeks. All evaluable patients were analyzed (placebo QW, n=10; exenatide QW 0.8 mg, n=10; exenatide QW 2.0 mg, n=9), unless otherwise stated. Steady-state plasma exenatide concentrations were observed by Week 8 of the study. For the evaluable pharmacokinetic population, geometric mean (90% confidence interval) steady-state plasma concentrations (pg/mL) were 81.2 (68.3-96.4) and 344.5 (256.5-462.7) with exenatide QW 0.8 mg (n=8) and exenatide QW 2.0 mg (n=5), respectively. Baseline-to-Week 10 glycemic improvements with placebo QW, exenatide QW 0.8 mg, and exenatide QW 2.0 mg, respectively, were: HbA(1c) (%): -0.4+/-0.3, -1.0+/-0.7, and -1.5+/-0.7; FPG (mg/dL): -20.5+/-20.4, -25.2+/-10.9, and -50.8+/-27.8; and 2-hour postprandial plasma glucose excursions (mg/dL): -8.8+/-26.9, -50.0+/-41.1, and -59.7+/-26.8 (means +/- SD). No serious adverse events (AEs) were reported and no AEs led to study discontinuation in any group. The most frequent AE observed was mild-to-moderate injection site induration. No serious hypoglycemia was reported. Exenatide QW for 10 weeks was well tolerated and improved short-term glycemic control in Japanese patients with suboptimally controlled T2D.
authors.affiliation: Lilly Research Laboratories Japan, Eli Lilly Japan K.K., Kobe, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Iwamoto
authors.forename: Risa
authors.initials: R
authors.lastname: Nasu
authors.forename: Ayuko
authors.initials: A
authors.lastname: Yamamura
authors.forename: Prajakti A
authors.initials: PA
authors.lastname: Kothare
authors.forename: Kenneth
authors.initials: K
authors.lastname: Mace
authors.forename: Anne M
authors.initials: AM
authors.lastname: Wolka
authors.forename: Helle
authors.initials: H
authors.lastname: Linnebjerg
mesh_terms: D000368:Aged; D000465:Algorithms; D044466:Asian People; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D000077270:Exenatide; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D007267:Injections; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics*; D010919:Placebos; D014688:Venoms / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics*
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D010455:Peptides; D010919:Placebos; D014688:Venoms; D000077270:Exenatide