Phase 1-2 Study of the Pharmacology of Exenatide in Pediatric Sepsis
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Exenatide associated adverse event occurence
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 1 Month 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 44 weeks estimated gestational age to 18 years AND
- •Admitted to the PICU for the sepsis event AND
- •Vascular catheter capable of providing serial blood samples in place AND
- •Diagnosis of septic shock = sepsis with cardiovascular organ dysfunction AND
- •Parents speak English or Spanish
排除标准
- •Greater than 12 hours from admission to PICU to enrollment OR
- •Chronic or acute dialytic therapy, history of renal impairment or renal transplantation OR
- •History of pancreatitis OR
- •History of hypersensitivity to Byetta OR
- •History of severe gastrointestinal disease or gastroparesis OR
- •History of diabetes mellitus, type I or type II OR
- •History of insulin, sulfonyl urea drugs, or coumarin use OR
- •History of hypoglycemia OR
- •History of active pregnancy (effect of exenatide on the fetus is unknown) OR
- •Inability to collect serial blood samples OR
- •Previously enrolled in the PEPS study OR
- •Lack of commitment to aggressive sepsis therapy OR
- •Expectation to succumb from the sepsis event OR
- •Patient is a foster child and/or ward of the state OR
- •Sepsis event associated with a PICU-acquired nosocomial infection OR
- •Patient is enrolled in another interventional investigation that might obscure the potential effects of exenatide dosing.
研究组 & 干预措施
Exenatide
Subjects dosed with exenatide in Phase 2
干预措施: Exenatide (Drug)
Exenatide vehicle
Subjects dosed with exenatide vehicle in Phase 2
干预措施: Exenatide vehicle (Drug)
结局指标
主要结局
Exenatide associated adverse event occurence
时间窗: From PICU admission to PICU discharge, an average interval of 7.5 days
Potential adverse events associated with exenatide: nausea, abdominal pain, hypoglycemia, delayed gastric emptying, pancreatitis, renal dysfunction, reactions at injection site. Adverse event occurence will be tabulated while the subject remains in the PICU.
Exenatide pharmacokinetics: Area under the exenatide concentration curve for 4 subcutaneous exenatide injections administered every 12 hours.
时间窗: 48 hours following the first exenatide dose
Delineation of the pharmacokinetics of subcutaneously dosed exenatide among children with de novo septic shock.
次要结局
- Exenatide clinical efficacy: Effect of exenatide on intensity and duration of pulmonary failure.(From onset to discontinuation of mechanical ventilator support, an average interval of 4.5 days)
- Exenatide pharmacodynamics: Effect of exenatide on glucose homeostasis(60 hours following first exenatide dose)
- Exenatide pharmacodynamics: Effect of exenatide on serum inflammatory cytokine concentrations.(60 hours following first exenatide dose)
- Exenatide clinical efficacy: Effect of exenatide on intensity and duration of organ dysfunctions.(From PICU admission to PICU discharge, an average interval of 7.5 days)
- Exenatide clinical efficacy: Effect of exenatide on intensity and duration of renal failure(From PICU admission to PICU discharge, an average interval of 7.5 days)
- Exenatide clinical efficacy: Effect of exenatide on intensity and duration of hemodynamic instability.(From onset to discontinuation of vasoactive-inotropic support, an average interval of 4 days)
- Exenatide clinical efficacy: Effect of exenatide on magnitude of sepsis-associated change in functional status.(2 measurements: baseline and PICU discharge, the latter occuring on average at 7.5 days)
- Exenatide clinical efficacy: Effect of exenatide on magnitude of sepsis-associated change in health-related quality of life(2 measurements: baseline and PICU discharge, the latter occuring on average at 7.5 days)
研究者
Jerry Zimmerman
Principal Investigator
Seattle Children's Hospital