NCT01573806

Pharmacology of Exenatide in Pediatric Sepsis

Phase 1-2 Study of the Pharmacology of Exenatide in Pediatric Sepsis

• Status: Withdrawn
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Seattle Children's Hospital · Academic / Other
• Sex: All
• Age: 1 Month – 18 Years
• Healthy volunteers: Not accepted

Summary

Pharmacology of Exenatide in Pediatric Sepsis, PEPS is a phase 1-2 research study that will examine drug safety, drug metabolism, drug action and preliminary drug clinical effects of four does of exenatide injected every 12 hours to children with shock from infection (septic shock). The investigators hypothesize that exenatide can be safely dosed to children with sepsis to achieve blood levels of drug similar to that achieved in teenagers with type 2 diabetes. The investigators further hypothesize that injection of exenatide to children with septic shock will normalize blood glucose levels and decrease levels of inflammation proteins in the blood during the early course of sepsis.

Detailed description

Pharmacology of Exenatide in Pediatric Sepsis, PEPS is a phase 1-2 investigation that will examine safety, pharmacokinetics, pharmacodynamics, and preliminary clinical efficacy of 4 subcutaneous doses of exenatide administered every 12 hours to children with newly diagnosed septic shock. The investigators' long term goal is to explore the potential benefit of exenatide on: early immunomodulation and glucose homeostasis, organ dysfunction, and clinically meaningful outcomes associated with pediatric sepsis. The current study objectives are to conduct a "3+3" dose escalation study, and then examine a "best exenatide allometric dose" to generate safety, pharmacokinetic, pharmacodynamic, and initial efficacy data in a larger cohort. In Phase 1 (three allometric doses; three age strata)the investigators will identify an exenatide dosing regimen that mimics area under the exenatide concentration curve for exenatide dosing among adolescents with type 2 diabetes with minimal or no adverse events. A total of 18 subjects are expected to be enrolled in Phase 1. In Phase 2 the investigators will utilize this "best exenatide allometric dose" to further clarify exenatide safety (adverse event occurence: e.g. nausea, abdominal pain, delayed gastric emptying, hypoglycemia, pancreatitis, renal dysfunction), pharmacokinetics, pharmacodynamics (glucose homeostasis; inflammatory cytokine serum concentrations), and effect on clinical outcomes (AUC of Saturation Index, AUC Vasoactive-Inotropic Score, AUC RIFLE Criteria, Pediatric Logistic Organ Dysfunction Score; changes in health-related quality of life and functional status). In Phase 2, 30 subjects in each age strata in the ratio of 4:1, exenatide: vehicle, are expected to be enrolled.

Conditions

• Septic Shock
• Inflammation
• Glucose Homeostasis
• Organ Dysfunction
• Health-related Quality of Life

Interventions

Type	Name	Description
DRUG	Exenatide	Exenatide, dosed subcutaneously every 12 hours for 4 doses
DRUG	Exenatide vehicle	Exenatide vehicle, dosed subcutaneously every 12 hours for 4 doses

Timeline

• Start date: 2012-10-01
• Primary completion: 2014-10-01
• Completion: 2014-10-01
• First posted: 2012-04-10
• Last updated: 2017-10-05

Locations

1 site across 1 country: United States