Clinical trial NCT01572649: Evaluation of the Blood Levels of the Drug (Lixisenatide), the Plasma Glucose Levels and Safety in Paediatric and Adult Patients With Type 2 Diabetes
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2012-04-06
Enrollment: 24
Sex: ALL
Minimum age (years): 10
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: D1 at each period up to 4h30 after study drug injection (8 timepoints)
Secondary outcomes:
measure: Pharmacokinetics: lixisenatide plasma concentration
timeFrame: 0 (predose), 30 min, 1h, 1h30, 2h30, 3h30, 4h30 and 6h30 post-dose at D1 of each study period (8 timepoints)
measure: Pharmacokinetic parameter (Cmax)
timeFrame: calculated over the period of timepoints at D1 of each study period
measure: Pharmacokinetic parameter (Tmax)
timeFrame: calculated over the period of timepoints at D1 of each study period
measure: Pharmacokinetic parameter (AUC last)
timeFrame: estimated over the period of timepoints at D1 of each study period
measure: Pharmacokinetic parameter (AUC)
timeFrame: extrapolated based on the period of timepoints at D1 of each study period
measure: 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
timeFrame: D1 at each period up to 4h30 after study drug injection (7 timepoints)
Other outcomes:
Locations:
city: Chula Vista
country: United States
facility: Investigational Site Number 840005
state: California
city: Overland Park
country: United States
facility: Investigational Site Number 840001
state: Kansas
city: Louisville
country: United States
facility: Investigational Site Number 840003
state: Kentucky
city: Puebla
country: Mexico
facility: Investigational Site Number 484001
city: Cape Town
country: South Africa
facility: Investigational Site Number 710002
city: Leeds
country: United Kingdom
facility: Investigational Site Number 826001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: