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

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

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.

Study Overview

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

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 1

Contacts and Locations

Study Locations

• Mauritius
  • Phoenix, Mauritius
    • Investigational Site Number 480001
• Mexico
  • Monterrey, Mexico, 64460
    • Investigational Site Number 484001
  • Puebla, Mexico, 72190
    • Investigational Site Number 484002
• South Africa
  • Cape Town, South Africa, 7530
    • Investigational Site Number 710001
• Spain
  • Barcelona, Spain, 08009
    • Investigational Site Number 724002
• Turkey
  • Ankara, Turkey, 06500
    • Investigational Site Number 792002
  • Izmir, Turkey, 35100
    • Investigational Site Number 792001
• United States
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808-4124
      • Investigational Site Number 840002
    • New Orleans, Louisiana, United States, 70115-6969
      • Investigational Site Number 840006
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Investigational Site Number 840009
  • Texas
    • Lufkin, Texas, United States, 75904
      • Investigational Site Number 840007

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lixisenatide; 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: Metformin; Pharmaceutical form: tablet Route of administration: oral; Drug: Lixisenatide (AVE0010); Pharmaceutical form: solution Route of administration: subcutaneous; Drug: Basal Insulin; Pharmaceutical form: solution Route of administration: subcutaneous
Placebo Comparator: Placebo; 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: Metformin; Pharmaceutical form: tablet Route of administration: oral; Drug: Placebo; Pharmaceutical form: solution Route of administration: subcutaneous; Drug: Basal Insulin; Pharmaceutical form: solution Route of administration: subcutaneous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Sanofi

Publications and helpful links

General Publications

• Barrientos-Perez M, Hsia DS, Sloan L, Nell H, Mungur O, Hovsepian L, Schmider W, Spranger R, Yang N, Niemoeller E. A study on pharmacokinetics, pharmacodynamics and safety of lixisenatide in children and adolescents with type 2 diabetes. Pediatr Diabetes. 2022 Sep;23(6):641-648. doi: 10.1111/pedi.13343. Epub 2022 Apr 24.

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2017
• Primary Completion (Actual): January 27, 2020
• Study Completion (Actual): January 27, 2020

Study Registration Dates

• First Submitted: June 14, 2016
• First Submitted That Met QC Criteria: June 14, 2016
• First Posted (Estimate): June 17, 2016

Study Record Updates

• Last Update Posted (Actual): April 25, 2022
• Last Update Submitted That Met QC Criteria: April 22, 2022
• Last Verified: April 1, 2022

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; Metformin; Lixisenatide
• Other Study ID Numbers: TDR14311; U1111-1176-6142 (Other Identifier: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No