A study on pharmacokinetics, pharmacodynamics and safety of lixisenatide in children and adolescents with type 2 diabetes

Abstract

Objective: The aim of this study was to investigate the pharmacokinetic, pharmacodynamic and safety profile of the glucagon-like peptide-1 receptor agonist, lixisenatide, for the treatment of type 2 diabetes (T2D) in pediatric individuals.

Materials and methods: In this Phase 1, multicenter, randomized, double-blind, placebo-controlled, parallel-group, ascending repeated dose study (NCT02803918), participants aged ≥10 and < 18 years were randomized 3:1 to receive once-daily lixisenatide in 2-week increments of 5, 10, and 20 μg (n = 18) or placebo (n = 5) for 6 weeks.

Results: Mean lixisenatide concentrations generally increased with increasing doses irrespective of anti-drug antibody (ADA) status; however, mean lixisenatide concentrations and inter-subject variability were higher for participants with positive ADA status. Improvements in fasting plasma glucose, post-prandial glucose, AUC0-4.5 , HbA1c , and body weight were observed with lixisenatide. Overall, the safety profile was consistent with the known profile in adults, with no unexpected side effects and no treatment-emergent adverse events resulting in death or discontinuation. The most common events in the lixisenatide group were vomiting (11.1%) and nausea (11.1%). No symptomatic hypoglycemia was reported in either group. No clinically significant hematologic, biochemical or vital sign abnormalities were observed.

Conclusions: Mean lixisenatide concentrations generally increased with increasing dose, irrespective of ADA status. Lixisenatide was associated with improved glycemic control and a trend in body weight reduction compared with placebo. The safety and tolerability profile of repeated lixisenatide doses of up to 20 μg per day in children and adolescents with T2D was reflective of the established safety profile of lixisenatide in adults.

Keywords: antidiabetic drug; clinical trial; pharmacodynamics; pharmacokinetics; type 2 diabetes.

Conflict of interest statement

M Barrientos‐Pérez—has served as an investigator for trials in pediatrics for Sanofi, Novo Nordisk, Eli Lilly, Janssen, OKPO and Boehringer Ingelheim; and has received honoraria for lectures from Pfizer, Abbott, Novo Nordisk and Eli Lilly. D Hsia—has no conflicts to disclose, funds related to the content of this study were paid directly to his institution. O Mungur—has no conflicts to disclose. H Nell—has no conflicts to disclose. L Sloan—has served as an investigator for Amgen, Boehringer Ingelheim, GSK, Janssen, Lilly, Merck and Sanofi. He serves on advisory boards for and has received honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Janssen and Lilly. L Hovsepian, R Spranger and N Yang—are employees of Sanofi. E Niemoeller and W Schmider—are employees of Sanofi and hold shares in Sanofi.

© 2022 The Authors. Pediatric Diabetes published by John Wiley & Sons Ltd.

Figures

FIGURE 1

Study design. †Placebo solution and volume to be injected matching to lixisenatide solution. R, randomization; ↑, onsite visit