title: Pharmacokinetics, Pharmacodynamics, and Safety of Luseogliflozin in Japanese Patients with Type 2 Diabetes Mellitus: A Randomized, Single-blind, Placebo-controlled Trial.
abstract: BACKGROUND
  Luseogliflozin, a potent, selective sodium glucose cotransporter 2 inhibitor, promotes urinary glucose excretion (UGE) and reduces plasma glucose concentrations. Luseogliflozin was approved for use in Japan after favorable pharmacokinetic, pharmacodynamic, and safety profiles were reported in healthy Japanese subjects and patients with type 2 diabetes mellitus (T2DM) in clinical development studies. We aimed to investigate the pharmacokinetics, pharmacodynamics, and safety of multiple doses of luseogliflozin administered once daily for 7 days in Japanese patients with T2DM.
  
  
  METHODS
  We conducted a randomized, placebo-controlled, single-blind, parallel-group, clinical pharmacology study at the P-One Clinic, Keikokai Medical Corporation (Tokyo, Japan) between August 2009 and November 2009. Forty Japanese patients with T2DM were randomly assigned to receive once-daily 0.5, 1, 2.5 or 5 mg luseogliflozin or placebo for 7 days. We assessed the pharmacokinetics, pharmacodynamics (including changes in UGE and plasma glucose concentrations), and safety of luseogliflozin.
  
  
  RESULTS
  The plasma concentrations of luseogliflozin and its active metabolite, M2, were dose proportional, without accumulation. 24-h UGE was greater in all luseogliflozin groups versus placebo. Least-squares mean differences in 24-h UGE on Day 7 increased dose dependently in the luseogliflozin groups, with values of 49.2, 66.5, 89.4, and 101 g/day at 0.5, 1, 2.5, and 5 mg, respectively. On Day 7, the areas under the concentration-time curves for post-meal plasma glucose and the mean plasma glucose for 0-16 h were significantly lower in all luseogliflozin groups versus placebo. Seven patients had mild adverse events (AEs); all were resolved. No AEs led to study discontinuation.
  
  
  CONCLUSIONS
  Once-daily administration of luseogliflozin for 7 days increased 24-h UGE in a dose-dependent manner, reduced plasma glucose concentrations, and was well tolerated in Japanese patients with T2DM. The pharmacokinetic and pharmacodynamic profile of luseogliflozin observed in this study supports its once-daily dosing regimen.
  
  
  BACKGROUND
  Taisho Pharmaceutical Co., Ltd.
authors: Institute of Clinical Medicine and Research, The Jikei University School of Medicine, 163-1 Kashiwashita, Kashiwa, Chiba, 277-8567, Japan.
authors: Takashi
authors: T
authors: Sasaki
authors: Yutaka
authors: Y
authors: Seino
authors: Atsushi
authors: A
authors: Fukatsu
authors: Michito
authors: M
authors: Ubukata
authors: Soichi
authors: S
authors: Sakai
authors: Yoshishige
authors: Y
authors: Samukawa
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People; D001786:Blood Glucose; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007564:Japan; D008297:Male; D008875:Middle Aged; D016037:Single-Blind Method; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013012:Sorbitol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013012:Sorbitol; C549343:1,5-anhydro-1-(5-(4-ethoxybenzyl)-2-methoxy-4-methylphenyl)-1-thioglucitol