A Study on Safety, Pharmacokinetics and Pharmacodynamics of Lixisenatide in Pediatric Patients With Type 2 Diabetes Mellitus (T2DM)

Study Overview
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Brief Summary
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Primary Objective: To demonstrate safety of 14-day repeated lixisenatide doses with 3 ascending doses as compared to placebo in pediatric patients with T2DM. Secondary Objectives: To evaluate plasma concentrations of lixisenatide after repeated doses (3 ascending doses) and pharmacokinetic parameters of repeated lixisenatide doses in pediatric patients with T2DM. To evaluate the change from baseline in fasting and post-prandial plasma glucose concentrations during a standardized meal test after 3 ascending repeated doses of lixisenatide in comparison to placebo.

Detailed Description
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The total study duration will be up to 10 weeks that includes a 6-week treatment period with dose escalation every 2 weeks.

Official Title
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Randomized, Double-blind, Placebo-controlled, Dose Escalation, Study on Safety, Pharmacokinetics and Pharmacodynamics of Lixisenatide in Pediatric Patients With Type 2 Diabetes Mellitus Not Adequately Controlled With Metformin and/or Basal Insulin

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Lixisenatide (AVE0010)
* Drug: Placebo
* Drug: Basal Insulin
* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : Male or female patients aged ≥10 and <18 years old (at least 4 patients below 16 years old). Body mass index (BMI) >85th percentile for age and gender; BMI ≤50 kg/m2. Male and female patients with documented T2DM insufficiently controlled with metformin at a stable dose and regimen for 8 weeks prior to randomization and/or basal insulin at stable dose (± 20%) and regimen for 8 weeks prior to randomization. The exact individual metformin dose will be selected according to local regulation and to the investigator's medical judgment. Glycated hemoglobin (HbA1c) >6.5% and ≤11% at screening. Exclusion criteria: If female, ongoing pregnancy (defined as positive serum pregnancy test), breast-feeding. Sexually active postmenarchal female patient who does not agree to use an adequate and highly effective method of contraception throughout the study duration and according to local regulation (ie, hormonal contraception, condom, etc.). Diabetes other than T2DM. Fasting plasma glucose >250 mg/dL (>13.9 mmol/L) at screening. Use of other oral or injectable antidiabetic or hypoglycemic agents other than metformin and basal insulin (eg, alpha glucosidase inhibitor, glucagon-like peptide (GLP-1) receptor agonist, dipeptidyl peptidase-IV (DPP-IV) inhibitors, short-acting insulin etc.) within 1 month prior to the screening visit. History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery, inflammatory bowel disease. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lixisenatide<br>Administration of 3 ascending repeated doses of lixisenatide once daily and subcutaneously. Background therapy (metformin and basal insulin) will be administered daily about the same time as usually done. | Drug: Lixisenatide (AVE0010)<br>* Pharmaceutical form: solution Route of administration: subcutaneous<br>Drug: Basal Insulin<br>* Pharmaceutical form: solution Route of administration: subcutaneous<br>Drug: Metformin<br>* Pharmaceutical form: tablet Route of administration: oral<br>|
| Placebo Comparator: Placebo<br>Administration of 3 ascending repeated doses of matching placebo once daily and subcutaneously. Background therapy (metformin and basal insulin) will be administered daily about the same time as usually done. | Drug: Placebo<br>* Pharmaceutical form: solution Route of administration: subcutaneous<br>Drug: Basal Insulin<br>* Pharmaceutical form: solution Route of administration: subcutaneous<br>Drug: Metformin<br>* Pharmaceutical form: tablet Route of administration: oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with adverse events (AEs) |  | Up to 10 weeks | 
| Number of patients with treatment-emergent adverse events (TEAEs) |  | Up to 10 weeks | 
| Number of patients with anti-lixisenatide antibodies |  | Up to 10 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of pharmacokinetic (PK) parameters: lixisenatide plasma concentration |  | Day 14, Day 28 and Day 42 | 
| Assessment of PK parameters: maximum concentration (Cmax) |  | Day 42 | 
| Assessment of PK parameters: time to reach Cmax (Tmax) |  | Day 42 | 
| Assessment of PK parameters: area under up to last concentration (AUClast) |  | Day 42 | 
| Assessment of PK parameters: area under curve (AUC) |  | Day 42 | 
| Assessment of pharmacodynamic parameter: plasma glucose AUC-0-4.5 hours |  | Day 14, Day 28 and Day 42 |