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

Study Overview
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Brief Summary
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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.

Official Title
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A Randomised, Double-blind, Placebo-controlled, Parallel Group Dose-finding Study of Linagliptin (1 and 5 mg Administered Orally Once Daily) Over 12 Weeks in Children and Adolescents, From 10 to 17 Years of Age, With Type 2 Diabetes Mellitus

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: placebo
* Drug: BI1356 low dose
* Drug: BI1356 high dose


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Paediatric patients (children and adolescents), aged 10 to 17 years with documented diagnosis of type 2 diabetes mellitus 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) Negative for islet cell antigen (ICA) auto-antibodies and glutamic acid decarboxylase (GAD) auto-antibodies C-peptide levels (serum) >= 1.5 ng/ml (at 90 min following a Boost challenge) Exclusion criteria: History of acute metabolic decompensation, such as diabetic ketoacidosis, within 3 months Current short-acting insulin or having received short-acting insulin for more than 3 days within 1 month prior to randomisation Treatment with weight reduction medications (including anti-obesity treatments)

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: linagliptin low dose<br>linagliptin low dose for children once daily | Drug: BI1356 low dose<br>* comparison of different dosages of drug (low vs high) vs placebo<br>|
| Experimental: linagliptin high dose<br>linagliptin high dose for children once daily | Drug: BI1356 high dose<br>* comparison of different dosages of drug (low vs high) vs placebo<br>|
| Placebo Comparator: placebo<br>matching placebo for each linagliptin dose once daily | Drug: placebo<br>* comparison of different dosages of drug (low vs high) vs placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Glycosylated Haemoglobin (HbA1c) (%) After 12 Weeks of Treatment | Change from baseline in Glycosylated haemoglobin (HbA1c) [%] after 12 weeks of treatment with double-blind trial medication. Baseline was defined as the last observation before the first intake of any double-blind randomised trial medication. The number of participants analysed displays the number of participants with available data at the timepoint of interest. | Baseline and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dipeptidyl-peptidase-4 (DPP-4) Inhibition (%) at Trough at Steady State | 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. | Baseline and 4 weeks or 8 weeks or 12 weeks | 
| Change From Baseline in Fasting Plasma Glucose (FPG) After 12 Weeks of Treatment | 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. | Baseline and 12 weeks |