Evaluation of the Blood Levels of the Drug (Lixisenatide), the Plasma Glucose Levels and Safety in Paediatric and Adult Patients With Type 2 Diabetes

A Randomized, Double-blind, Placebo Controlled Trial to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Lixisenatide in Paediatric (10 - 17 Years Old) and Adult Patients With Type 2 Diabetes

Primary Objective:

- To investigate the effects of two single subcutaneous lixisenatide doses (5 and 10 µg) as compared to placebo in reducing postprandial glucose (PPG) in type 2 diabetic paediatric population (10-17 years old) and adults as controls

Secondary Objectives:

- To evaluate in both paediatric and adult populations:

• the blood levels of lixisenatide (pharmacokinetic) parameters in plasma after single subcutaneous ascending doses
• the maximum post-prandial glucose excursion, and on the changes in insulin, C-peptide and glucagon plasma concentrations following a standardized breakfast
• safety and tolerability.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Placebo; Drug: Lixisenatide (AVE0010)

Detailed Description

The duration of the study for each patient is planned between 4 and 7 weeks including a screening period (25 to 30 days), 3 treatment periods 1-7 days apart, each period lasting only one day (Day 1) and an end-of-study visit between 1 to 7 days after the last dose administration.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Mexico
  • Puebla, Mexico, 72190
    • Investigational Site Number 484001
• South Africa
  • Cape Town, South Africa, 7530
    • Investigational Site Number 710002
• United Kingdom
  • Leeds, United Kingdom, LS2 9LH
    • Investigational Site Number 826001
• United States
  • California
    • Chula Vista, California, United States, 91911
      • Investigational Site Number 840005
  • Kansas
    • Overland Park, Kansas, United States, 66212
      • Investigational Site Number 840001
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Investigational Site Number 840003

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria :

• Male or female patients with type 2 diabetes mellitus, as defined by WHO (fasting plasma glucose ≥ 7 mmol/L (126mg/dL) or 2 hours postprandial plasma glucose ≥ 11.1 mmol/L (200 mg/dL)), diagnosed for at least 1 year (adults) and at least 3 months for paediatric population at the time of screening visit, with or without metformin (stable dose ± 10 % for at least 4 weeks prior to randomization)
• HbA1c ≥ 7% and ≤ 10% at screening
• Age eligibility for paediatric population: ≥ 10 years and <18 years with at least 3 patients below 15 years and no more than 3 patients aged between 16 and 18 years; Age eligibility for adults: ≥ 18 and ≤ 65 years
• For paediatric population:body weight >50kg, BMI >85th percentile for age and gender and BMI ≤ 50 kg/m²
• For adults: BMI > 25 kg/m2 and ≤ 37 kg/m2

Exclusion criteria:

• If female, pregnancy (defined as positive serum pregnancy test), breast-feeding
• Diabetes other than type 2 diabetes
• Positive test for insulinoma associated protein (IA2) and glutamic acid decarboxylase (GAD) autoantibodies
• Use of other oral or injectable antidiabetic or hypoglycemic agents other than metformin (e.g., alpha glucosidase inhibitor, exenatide, DPP-IV inhibitors, insulin etc.) within 3 months prior to the time of screening
• Allergic reaction to any GLP-1 agonist in the past (e.g. exenatide, liraglutide) or to metacresol
• History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery, inflammatory bowel disease
• Personal or family history of medullary thyroid cancer (MTC) or genetic conditions that predispose to MTC (e.g., multiple endocrine neoplasia syndromes)

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; 1 single administration (volume matched to the dose lixisenatide: 50 µL or 100µL) once a day subcutaneously	Drug: Placebo; Pharmaceutical form:Solution for injection Route of administration: subcutaneous
Experimental: Dose 1; 1 single administration of 5 µg lixisenatide (50 µL) once a day subcutaneously	Drug: Lixisenatide (AVE0010); Pharmaceutical form:Solution for injection Route of administration: subcutaneous
Experimental: Dose 2; 1 single administration of 10 µg lixisenatide (100 µL) once a day subcutaneously	Drug: Lixisenatide (AVE0010); Pharmaceutical form:Solution for injection Route of administration: subcutaneous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
GLU-AUC 0:30-4:30h: area under the plasma glucose concentration time profile from time of the standardized breakfast start (30 min after IMP injection and pre-meal plasma glucose) until 4 hours later subtracting the pre-meal value	D1 at each period up to 4h30 after study drug injection (8 timepoints)

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics: lixisenatide plasma concentration	0 (predose), 30 min, 1h, 1h30, 2h30, 3h30, 4h30 and 6h30 post-dose at D1 of each study period (8 timepoints)
Pharmacokinetic parameter (Cmax)	calculated over the period of timepoints at D1 of each study period
Pharmacokinetic parameter (Tmax)	calculated over the period of timepoints at D1 of each study period
Pharmacokinetic parameter (AUC last)	estimated over the period of timepoints at D1 of each study period
Pharmacokinetic parameter (AUC)	extrapolated based on the period of timepoints at D1 of each study period
Area under the concentration time profile from time of standardized breakfast start (30 min after IMP injection) until 4 hours later for insulin, C-peptide and glucagon	D1 at each period up to 4h30 after study drug injection (7 timepoints)

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: April 4, 2012
• First Submitted That Met QC Criteria: April 4, 2012
• First Posted (Estimate): April 6, 2012

Study Record Updates

• Last Update Posted (Estimate): May 23, 2014
• Last Update Submitted That Met QC Criteria: May 22, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Lixisenatide
• Other Study ID Numbers: PKD11475; 2011-004584-67 (EudraCT Number); U1111-1124-3136 (Other Identifier: UTN)