Phase 1
N=26
Safety Study of Lisinopril in Children and Adolescents With a Kidney Transplant
Hypertension
Bottom Line
View on ClinicalTrials.gov: NCT01491919 ↗Enrolled (actual)
26
Serious AEs
4.6%
Results posted
Jul 2015
Primary outcome: Primary: Pharmacokinetics (PK) - Area Under the Plasma Concentration-time Curve (AUC) — 298; 640; 702 ng*h/mL
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Lisinopril (Drug)
- Age
- Pediatric · 2+ yrs
- Sex
- All
- Sponsor
- Uptal Patel
- Primary completion
- Sep 2013
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Pharmacokinetics (PK) - Area Under the Plasma Concentration-time Curve (AUC) |
298; 640; 702 | — |
| PRIMARY PK - Maximum Observed Concentration of Drug in Plasma (Cmax) |
20.9; 47.7; 58.0 | — |
| PRIMARY PK - Time of the Maximum Observed Concentration in Plasma (Tmax) |
5.0; 5.0; 4.5 | — |
| PRIMARY PK - Oral Clearance (CL/F) |
17.9; 18.6; 32.8 | — |
| PRIMARY PK Renal Clearance (CLrenal) |
3.4; 3.4; 6.8 | — |
| PRIMARY Number of Adverse Events (AEs) and Serious Adverse Events (SAEs) During/After Study Drug Administration |
12; 12; 5; 0; 7; 12 | — |
| SECONDARY Change in Potassium Level From Baseline in Lisinopril-naive Participants |
0.1; -0.3; 0.3 | — |
| SECONDARY Worse Post-dose Decrease in Estimated Glomerular Filtration Rate (eGFR) From Baseline in Lisinopril-naive Participants |
1; 1.02; 0.89 | — |
| SECONDARY Largest eGFR Percent Decrease From Baseline in Lisinopril-naive Participants |
15; 12; 21 | — |
| SECONDARY Change in Urine Protein/Creatinine From Baseline in Lisinopril-naive Participants. |
-0.45; -0.08; -0.74 | — |
| SECONDARY Change in Diastolic Blood Pressure From Baseline in Lisinopril-naive Participants |
-4.0; 7.0; NA; -9.0; -6.0; -4.0 | — |
| SECONDARY Change in Systolic Blood Pressure From Baseline in Lisinopril-naive Participants |
-5.0; -6.0; NA; -6.7; -8.8; -11.3 | — |
| SECONDARY Change in Systolic Blood Pressure (BP) From Baseline in Lisinopril SOC Group |
-6.0; -1.0; 6.4; -1.0 | — |
| SECONDARY Change in Diastolic Blood Pressure From Baseline in Lisinopril SOC Group |
-6.0; -6.5; 3.4; -3.0 | — |
Summary
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.
Eligibility Criteria
Inclusion Criteria
- 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 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).
Exclusion Criteria
- 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
- Pregnancy
Data sourced from ClinicalTrials.gov (NCT01491919). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.