Clinical trial simulations in pediatric patients using realistic covariates: application to teduglutide, a glucagon-like peptide-2 analog in neonates and infants with short-bowel syndrome.

Abstract

Teduglutide, a synthetic glucagon-like peptide-2 (GLP-2) analog with activity relating to the regeneration, maintenance, and repair of the intestinal epithelium, is currently being evaluated for the treatment of short-bowel syndrome (SBS), Crohn's disease, and other gastrointestinal disorders. On the basis of promising results from teduglutide studies in adults with SBS and from studies in neonatal and juvenile animal models, a pediatric multiple-dose phase I clinical study was designed to determine the safety, efficacy, and pharmacokinetics of teduglutide in pediatric patients with SBS who have undergone resection for necrotizing enterocolitis, malrotation, or intestinal atresia. This report details the application of clinical trial simulations coupled with a novel approach using generalized additive modeling for location, scale, and shape (GAMLSS) that facilitates the simulation of demographic covariates specific to the targeted patient populations. The goal was to optimize phase I dosing strategies and the likelihood of achieving target exposure and therapeutic effect.

• Authors: M S Mouksassi, J F Marier, J Cyran, A A Vinks
• Journal: Clinical pharmacology and therapeutics (Clin Pharmacol Ther) Vol. 86 Issue 6 Pg. 667-71 (Dec 2009) ISSN: 1532-6535 [Electronic] United States
• PMID: 19847163 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Gastrointestinal Agents
• Glucagon-Like Peptide 2
• Peptides
• teduglutide

Topics

• Adult
• Age Factors
• Body Weight
• Clinical Trials, Phase I as Topic
• Computer Simulation
• Drug Dosage Calculations
• Gastrointestinal Agents (administration & dosage, pharmacokinetics)
• Glucagon-Like Peptide 2 (administration & dosage, pharmacokinetics)
• Humans
• Infant
• Infant, Newborn
• Models, Biological
• Peptides (administration & dosage, pharmacokinetics)
• Short Bowel Syndrome (drug therapy)
• Treatment Outcome