Safety and Pharmacokinetics of Lisinopril in Pediatric Kidney Transplant Recipients
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 26
- 试验地点
- 7
- 主要终点
- Number of Adverse Events (AEs) and Serious Adverse Events (SAEs) During/After Study Drug Administration
研究概览
简要总结
The drug lisinopril is approved by the U.S. Food and Drug Administration for the treatment of high blood pressure, heart failure, and acute heart attacks in adult patients. In children over 6 years of age, lisinopril is approved for the treatment of high blood pressure. Lisinopril is in a group of medications called angiotensin-converting enzyme inhibitors (ACE). ACE inhibitors such as lisinopril work by decreasing certain chemicals that tighten the blood vessels so blood flows more smoothly and the heart can pump blood more efficiently.
There is some information available about how children with high blood pressure absorb, distribute, metabolize, and eliminate lisinopril (this information about medication processing by the body is called pharmacokinetic data). However, there is no information about how children with high blood pressure who have received a kidney transplant process lisinopril. In addition to decreasing blood pressure, investigators believe that lisinopril may help kidney transplants work longer by reducing the activity of chemicals made by cells in kidney transplants that can lead to inflammation and injury. Such benefits have not been found with another group of blood pressure medications called calcium channel blockers, which are the most commonly used medication group to control high blood pressure in children after a kidney transplant. A clinical trial will be conducted in the future to compare which medication group helps kidney transplants in children last longer. To guide the selection of the best dose to test in future studies, investigators in this study will try to determine the safety profile, dose tolerability, and pharmacokinetics of lisinopril in children and adolescents (2-17 years of age) who have received a kidney transplant and have high blood pressure.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Kidney transplant recipient
- •Age 2-17 years, inclusive, at the time of first study dose
- •Estimated GFR (eGFR) ≥30 ml/min/1.73m2, with stable allograft function as indicated by <20% change in serum creatinine in the previous 30 days
- •Stable immunosuppressive regimen, as indicated by <10% change in dosage (in mg/kg) in these medications, within the 14 days prior to enrollment
- •Systolic BP >90th percentile for age, gender, and height, necessitating initiation or addition of an antihypertensive medication
- •For females of child-bearing potential, a negative serum pregnancy test prior to initial dosing and agreement to practice appropriate contraceptive measures, including abstinence, from the time of the initial pregnancy testing through the remainder of the study (30 days after last administration of investigational agents).
排除标准
- •History of anaphylaxis attributable to lisinopril or other angiotensin-converting enzyme inhibitor (ACEI) agents (e.g.,enalapril, ramipril, quinapril)
- •History of anaphylaxis attributable to iohexol or an iodine hypersensitivity
- •Use of an angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker, or renin antagonist within 30 days prior to enrollment
- •Stage 2 hypertension defined as the >99th percentile for age, height and gender + 5 mm Hg
- •Blood Potassium value > 6.0 milliequivalent / liter (mEq/L) (as determined at the screening visit)
- •Previous participation in this study
- •Physician concern that the participant may not adhere to the study protocol, based on prior behavior
- •Current plasmapheresis treatment
- •History of angioedema
研究组 & 干预措施
Low Dose: Lisinopril
Participants will receive study medication for 14±3 days at a dose 0.1 mg/kg/day
干预措施: Lisinopril (Drug)
Medium Dose: Lisinopril
Participants will receive study medication for 14±3 days at a dose 0.2 mg/kg/day
干预措施: Lisinopril (Drug)
High Dose: Lisinopril
Participants will initially receive study medication at 0.2 mg/kg/day for 5±2 days. If blood tests exclude drug-related toxicity, then the lisinopril dose will be increased to 0.4 mg/kg/day and participants will continue to complete the 14±3 day Treatment Period.
干预措施: Lisinopril (Drug)
结局指标
主要结局
Number of Adverse Events (AEs) and Serious Adverse Events (SAEs) During/After Study Drug Administration
时间窗: First dose of study drug to 30 days after final study visit for AEs and until resolution for SAEs
Number of Adverse Events (AEs) related and not related to study drug; number of Serious Adverse Events (SAEs) related and not related to study drug
PK - Maximum Observed Concentration of Drug in Plasma (Cmax)
时间窗: Day14 (+/- 3 d) of dose at 0 hour and 1, 2, 4, 5, 8, 12, and 24 hrs after dose
At the Day 14 (±3 days) visit, blood (1 mL) will be collected at 0 hour (pre-dose) and at 1, 2, 4, 5, 8, 12 and 24 hours post-lisinopril dose for determination of Cmax. Geometric mean was calculated from all measurements.
PK - Time of the Maximum Observed Concentration in Plasma (Tmax)
时间窗: Day 14 (+/- 3 d) of dose at 0 hour and 1, 2, 4, 5, 8, 12, and 24 hrs after dose
At the Day 14 (±3 days) visit, blood (1 mL) will be collected at 0 hour (pre-dose) and at 1, 2, 4, 5, 8, 12 and 24 hours post-lisinopril dose for determination of plasma lisinopril concentration. Medium was calculated from all measurements.
PK - Oral Clearance (CL/F)
时间窗: Day 14 (+/- 3 d) of dose at 0 hour and at 1, 2, 4, 5, 8, 12, and 24 hrs after dose
At the Day 14 (±3 days) visit, blood (1 mL) will be collected at 0 hour (pre-dose) and at 1, 2, 4, 5, 8, 12 and 24 hours post-lisinopril dose for determination of CL/F. Geometric mean was calculated from all measurements.
Pharmacokinetics (PK) - Area Under the Plasma Concentration-time Curve (AUC)
时间窗: Day 14 (+/- 3 days) of lisinopril therapy at hours 0 (pre-dose) and 1,2,4,5,8,12 and 24 hrs after dose
At the Day 14 (±3 days) visit, blood (1 mL) will be collected at 0 hour (pre-dose) and at 1, 2, 4, 5, 8, 12 and 24 hours post-lisinopril dose for determination of AUC. Geometric mean was calculated from all measurements.
PK Renal Clearance (CLrenal)
时间窗: Day 14 (+/- 3 d) of dose at 0 hour and 1, 2, 4, 5, 8, 12, and 24 hrs after dose.
At the Day 14 (±3 days) visit, blood (1 mL) will be collected at 0 hour (pre-dose) and at 1, 2, 4, 5, 8, 12 and 24 hours post-lisinopril dose for determination of CLrenal. Geometric mean was calculated from all measurements.
次要结局
- Change in Urine Protein/Creatinine From Baseline in Lisinopril-naive Participants.(Baseline to worst post-dose before Day 14 (+/- 3 days))
- Change in Potassium Level From Baseline in Lisinopril-naive Participants(At baseline visit and Day 14 prior to final study dose.)
- Worse Post-dose Decrease in Estimated Glomerular Filtration Rate (eGFR) From Baseline in Lisinopril-naive Participants(Baseline to Day 14 (+/- 3 days))
- Largest eGFR Percent Decrease From Baseline in Lisinopril-naive Participants(Baseline to Day 14 (+/- 3 days))
- Change in Systolic Blood Pressure (BP) From Baseline in Lisinopril SOC Group(Screening to Day 14 to 40)
- Change in Diastolic Blood Pressure From Baseline in Lisinopril SOC Group(Screening to Day 14 to 40)
- Change in Diastolic Blood Pressure From Baseline in Lisinopril-naive Participants(Baseline to Day 14 (+/-3 days))
- Change in Systolic Blood Pressure From Baseline in Lisinopril-naive Participants(Baseline to Day 14 (+/- 3 days))
研究者
Uptal Patel
Assoc Professor of Medicine
Duke University