Finding a Safe and Effective Dose of Linagliptin in Pediatric Patients With Type 2 Diabetes

• Dipeptidyl-peptidase-4 (DPP-4) Inhibition (%) at Trough at Steady State [ Time Frame: Baseline and 4 weeks or 8 weeks or 12 weeks ] [ Designated as safety issue: No ]
  DPP-4 inhibition (%) at trough at steady state is the relative change between the measurement of DPP-4 activity taken 0.5 hours before dosing at baseline and the first available on-treatment measurement of DPP-4 activity taken 0.5 hour before dosing at week 4, 8 or 12: DPP-4 inhibition (%) = 100 - (DPP-4 activity at week X / DPP-4 activity at baseline) x 100.
• Change From Baseline in Fasting Plasma Glucose (FPG) After 12 Weeks of Treatment [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  Change from baseline in FPG (mmol/L) after 12 weeks of treatment with double-blind trial medication. The number of participants analysed displays the number of participants with available data at the timepoint of interest.

The main objective of this study is to identify the dose of linagliptin in paediatric patients.

Other efficacy objectives include the comparison of the lowering effect of linagliptin low dose, high dose and placebo on the fasting plasma glucose (FPG) observed after 12 wk of treatment.

Furthermore, the study will investigate the pharmacokinetics (PK), the pharmacodynamics (PD) and the PK/PD relationship of linagliptin in the paediatric population.

• Drug: placebo
  comparison of different dosages of drug (low vs high) vs placebo
• Drug: BI1356 low dose
  comparison of different dosages of drug (low vs high) vs placebo
• Drug: BI1356 high dose
  comparison of different dosages of drug (low vs high) vs placebo

• Experimental: linagliptin low dose
  linagliptin low dose for children once daily
  Intervention: Drug: BI1356 low dose
• Experimental: linagliptin high dose
  linagliptin high dose for children once daily
  Intervention: Drug: BI1356 high dose
• Placebo Comparator: placebo
  matching placebo for each linagliptin dose once daily
  Intervention: Drug: placebo

Inclusion criteria:

1. Paediatric patients (children and adolescents), aged 10 to 17 years with documented diagnosis of type 2 diabetes mellitus
2. Insufficient glycaemic control (i.e. an HbA1c > 6.5% and <= 10.5%) despite treatment with diet and exercise and/or metformin (>= 1000 mg per day (or the maximum tolerated dose) at a stable dose or dosing frequency for 8 weeks prior to randomisation) and/or concomitant stable basal insulin (total daily dose must be <= 0.5U/kg with less than 10% of weekly dose change for 12 weeks prior to randomisation)
3. Negative for islet cell antigen (ICA) auto-antibodies and glutamic acid decarboxylase (GAD) auto-antibodies
4. C-peptide levels (serum) >= 1.5 ng/ml (at 90 min following a Boost challenge)

Exclusion criteria:

1. History of acute metabolic decompensation, such as diabetic ketoacidosis, within 3 months
2. Current short-acting insulin or having received short-acting insulin for more than 3 days within 1 month prior to randomisation
3. Treatment with weight reduction medications (including anti-obesity treatments)