title: Design, statistical analysis and sample size calculation of a phase IIb/III study of linagliptin versus voglibose and placebo.
abstract: BACKGROUND
  Many patients with diabetes mellitus (DM) require a combination of antidiabetic drugs with complementary mechanisms of action to lower their hemoglobin A1c levels to achieve therapeutic targets and reduce the risk of cardiovascular complications. Linagliptin is a novel member of the dipeptidyl peptidase-4 (DPP-4) inhibitor class of antidiabetic drugs. DPP-4 inhibitors increase incretin (glucagon-like peptide-1 and gastric inhibitory polypeptide) levels, inhibit glucagon release and, more importantly, increase insulin secretion and inhibit gastric emptying. Currently, phase III clinical studies with linagliptin are underway to evaluate its clinical efficacy and safety. Linagliptin is expected to be one of the most appropriate therapies for Japanese patients with DM, as deficient insulin secretion is a greater concern than insulin resistance in this population. The number of patients with DM in Japan is increasing and this trend is predicted to continue. Several antidiabetic drugs are currently marketed in Japan; however there is no information describing the effective dose of linagliptin for Japanese patients with DM.
  
  
  METHODS
  This prospective, randomized, double-blind study will compare linagliptin with placebo over a 12-week period. The study has also been designed to evaluate the safety and efficacy of linagliptin by comparing it with another antidiabetic, voglibose, over a 26-week treatment period. Four treatment groups have been established for these comparisons. A phase IIb/III combined study design has been utilized for this purpose and the approach for calculating sample size is described.
  
  
  CONCLUSIONS
  This is the first phase IIb/III study to examine the long-term safety and efficacy of linagliptin in diabetes patients in the Japanese population.
authors.affiliation: Biostatistics division, Graduate School of Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan. horiey@kaw.boehringer-ingelheim.com
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Horie
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Hayashi
authors.forename: Klaus
authors.initials: K
authors.lastname: Dugi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Takeuchi
mesh_terms: D003627:Data Interpretation, Statistical; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D004311:Double-Blind Method; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007294:Inositol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010919:Placebos; D011446:Prospective Studies; D012107:Research Design; D018401:Sample Size
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D010919:Placebos; D007294:Inositol; C102817:voglibose