Pharmacokinetic Single Dose Trial of Empagliflozin in Children and Adolescents With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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The aim of the study is to generate pharmacokinetic and pharmacodynamic data to identify the safe-effective dose of empagliflozin in children and adolescents aged 10 to less than 18 years with type 2 diabetes mellitus.

Official Title
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An Open-label, Randomised, Multicentre, Single-dose, Parallel Group Trial to Evaluate Pharmacokinetics and Pharmacodynamics of Empagliflozin in Children and Adolescents From 10 to Less Than 18 Years of Age With Type 2 Diabetes Mellitus

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: empagliflozin medium dose
* Drug: empagliflozin high dose
* Drug: empagliflozin low dose


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Children and adolescents with type 2 diabetes mellitus Insufficient glycaemic control (HbA1c <=10.5%) despite diet and exercise and/or metformin and/or stable basal or MDI insulin Negative for Islet Cell Antigen and Glutamic Acid Decarboxylase autoantibodies and fasting C-peptide levels >= 0.85 ng/ml BMI > 50th percentile for age and sex Exclusion criteria: Uncontrolled hyperglycaemia with a glucose level > 240 mg/dl (> 13.3 mmol/l) History of acute metabolic decompensation such as diabetic ketoacidosis within 3 months before the screening visit with the exception of acute de-compensation at the time of type 2 diabetes diagnosis Treatment with weight reduction medications within 4 weeks before randomisation

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: empagliflozin high dose<br>Patient to receive a high dose of empagliflozin | Drug: empagliflozin high dose<br> <br> |
| Experimental: empagliflozin medium dose<br>Patient to receive a medium dose of empagliflozin | Drug: empagliflozin medium dose<br> <br> |
| Experimental: empagliflozin low dose<br>Patient to receive a low dose of empagliflozin | Drug: empagliflozin low dose<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-inf | Area under the concentration-time curve of analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf). | Before drug administration (-0:30 hours (h)) and 0:30h, 1:00h, 1:30h, 2:00h, 4:00h, 8:00h, 12:00 (Day 1), 24:00 (Day 2), 34:00 (Day 2), 48:00 (Day 3) after drug administration. | 
| AUC0-tz | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable concentration (AUC0-tz). | Before drug administration (-0:30 hours (h)) and 0:30h, 1:00h, 1:30h, 2:00h, 4:00h, 8:00h, 12:00 (Day 1), 24:00 (Day 2), 34:00 (Day 2), 48:00 (Day 3) after drug administration. | 
| Cmax | Maximum measured concentration in plasma (Cmax). | Before drug administration (-0:30 hours (h)) and 0:30h, 1:00h, 1:30h, 2:00h, 4:00h, 8:00h, 12:00 (Day 1), 24:00 (Day 2), 34:00 (Day 2), 48:00 (Day 3) after drug administration. | 
| Tmax | Maximum measured concentration in plasma (tmax). | Before drug administration (-0:30 hours (h)) and 0:30h, 1:00h, 1:30h, 2:00h, 4:00h, 8:00h, 12:00 (Day 1), 24:00 (Day 2), 34:00 (Day 2), 48:00 (Day 3) after drug administration. | 
| t1/2 | Terminal half-life in plasma (t1/2). | Before drug administration (-0:30 hours (h)) and 0:30h, 1:00h, 1:30h, 2:00h, 4:00h, 8:00h, 12:00 (Day 1), 24:00 (Day 2), 34:00 (Day 2), 48:00 (Day 3) after drug administration. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Urinary Glucose Excretion (UGE) Over 24 h After Study Drug Intake | Change from baseline in Urinary Glucose Excretion (UGE) over 24 h after study drug intake. For the changes from baseline in UGE on Day 1 (0 to 24 h postdose) , adjusted means per treatment group were to be calculated based on an ANCOVA including 'treatment' as a fixed effect and 'UGE at baseline' and 'FPG at baseline' as continuous covariates. Means presented are the adjusted means. | baseline and 24 hours | 
| Change From Baseline in Fasting Plasma Glucose (FPG) at 24 h After Study Drug Intake | Change from baseline in Fasting Plasma Glucose (FPG) at 24h after study drug intake. For the change from baseline in FPG at 24 h postdose (in the morning of Day 2), adjusted means per treatment group were to be calculated based on an ANCOVA including 'treatment' as a fixed effect and 'FPG at baseline' as continuous covariate. Means presented are the adjusted means. | baseline and 24 hours | 
| Change From Baseline in 8-point Plasma Glucose Profile Over 24 h After Study Drug Intake | Change from baseline in 8-point plasma glucose profile over 24h after study drug intake (as defined by change from baseline in Mean Daily Glucose (MDG) calculated at Day 1). For the changes from baseline in MDG on Day 1, adjusted means per treatment group were to be calculated based on an ANCOVA including 'treatment' as fixed effect and 'MDG at baseline' as continuous covariate. Means presented are the adjusted means. | baseline and 24 hours |