A Randomised, Placebo-controlled, Double-blind, Semi-sequential Dose Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Repeated Escalating Subcutaneous Doses of Glutazumab in Subjects with Type 2 Diabetes

This study will be a multi-centre, double-blind, semi-sequential group, placebo-controlled, doseescalation study to assess the safety, tolerability and PK/PD of glutazumab in subjects with T2D. Four sequential cohorts, each with 6 subjects receiving glutazumab and 2 subjects receiving placebo, will be given increasing doses of glutazumab once weekly for 8 weeks (8 SC injections). The doses administered will be 5, 10, 20, and 30 mg once weekly. Prior to each dose escalation a Safety Review Committee (SRC) will meet to confirm the next dose level. A next dose level can only be started when all subjects in the preceding dose level have completed 4 weeks of dosing. Based on safety and PK data of these subjects a fifth cohort will be treated with a dose of glutazumab that will be determined by the SRC to be the most promising based on a risk-benefit evaluation. After Screening, subjects will undergo a 4-week single-blind run-in period. All background diabetes medication will be kept constant. At the end of the single-blind run-in period, subjects will be randomised 3:1 to receive either glutazumab or placebo, and the 8-week double-blind treatment period will begin. During the study, subjects will be reimbursed for their meals, parking during their visits, and investigator and research nurses will keep in close contact with subjects by weekly phone call and regular email to ensure the adherence to the study .