Safety Study of Lisinopril in Children and Adolescents With a Kidney Transplant (PTN_LISINO)

This study has been completed.
Sponsor:
Collaborators:
The EMMES Corporation
University of Rochester
OpAns, LLC
Information provided by (Responsible Party):
Uptal Patel, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT01491919
First received: November 29, 2011
Last updated: June 15, 2015
Last verified: June 2015
Results First Received: April 27, 2015  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Pharmacokinetics Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Hypertension
Intervention: Drug: Lisinopril

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Low Dose: Lisinopril Participants will receive study medication for 14±3 days at a dose 0.1 mg/kg/day
Medium Dose: Lisinopril Participants will receive study medication for 14±3 days at a dose 0.2 mg/kg/day
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.

Participant Flow:   Overall Study
    Low Dose: Lisinopril     Medium Dose: Lisinopril     High Dose: Lisinopril  
STARTED     13     10     3  
COMPLETED     12     8     2  
NOT COMPLETED     1     2     1  
Insufficient PK sampling                 1                 2                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Low Dose: Lisinopril Participants will receive study medication for 14±3 days at a dose 0.1 mg/kg/day
Medium Dose: Lisinopril Participants will receive study medication for 14±3 days at a dose 0.2 mg/kg/day
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.
Total Total of all reporting groups

Baseline Measures
    Low Dose: Lisinopril     Medium Dose: Lisinopril     High Dose: Lisinopril     Total  
Number of Participants  
[units: participants]
  12     8     2     22  
Age  
[units: years]
Mean (Standard Deviation)
  14.9  (2.3)     13.0  (3)     9.5  (3.5)     13.8  (3)  
Gender  
[units: participants]
       
Female     4     2     1     7  
Male     8     6     1     15  
Race (NIH/OMB)  
[units: participants]
       
American Indian or Alaska Native     0     1     0     1  
Asian     0     0     0     0  
Native Hawaiian or Other Pacific Islander     0     0     0     0  
Black or African American     3     4     0     7  
White     7     2     2     11  
More than one race     0     0     0     0  
Unknown or Not Reported     2     1     0     3  
Region of Enrollment  
[units: participants]
       
United States     12     8     2     22  
Estimated glomerular filtration rate (eGFR) [1]
[units: ml/minĀ perĀ 1.73m^2]
Mean (Standard Deviation)
  72.5  (25.7)     62  (16.7)     89.3  (44.4)     70.2  (24.4)  
Time since transplant  
[units: years]
Mean (Standard Deviation)
  4.8  (4.7)     4.9  (3.4)     0.9  (0.4)     4.5  (4.1)  
Ethnicity  
[units: participants]
       
Hispanic/Latino     2     2     0     4  
Non-hispanic/non-latino     10     6     2     18  
Weight  
[units: kg]
Mean (Standard Deviation)
  56.8  (19.4)     50.2  (28.7)     23.1  (3.0)     51.3  (23.8)  
[1]

Estimated glomerular filtration rate (eGFR) calculated by modified Schwartz formula [=0.413 x Length (cm)/serum creatinine (mg/dl)].

Note: text verified with protocol on 4/2/15 as '413xLength'. Added spaces for clarification.




  Outcome Measures
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1.  Primary:   Pharmacokinetics (PK) - Area Under the Plasma Concentration-time Curve (AUC)   [ Time Frame: Day 14 (+/- 3 days) of lisinopril therapy at hours 0 (pre-dose) and 1,2,4,5,8,12 and 24 hrs after dose ]

2.  Primary:   PK - Maximum Observed Concentration of Drug in Plasma (Cmax)   [ Time Frame: Day14 (+/- 3 d) of dose at 0 hour and 1, 2, 4, 5, 8, 12, and 24 hrs after dose ]

3.  Primary:   PK - Time of the Maximum Observed Concentration in Plasma (Tmax)   [ Time Frame: Day 14 (+/- 3 d) of dose at 0 hour and 1, 2, 4, 5, 8, 12, and 24 hrs after dose ]

4.  Primary:   PK - Oral Clearance (CL/F)   [ Time Frame: Day 14 (+/- 3 d) of dose at 0 hour and at 1, 2, 4, 5, 8, 12, and 24 hrs after dose ]

5.  Primary:   PK Renal Clearance (CLrenal)   [ Time Frame: Day 14 (+/- 3 d) of dose at 0 hour and 1, 2, 4, 5, 8, 12, and 24 hrs after dose. ]

6.  Primary:   Number of Adverse Events (AEs) and Serious Adverse Events (SAEs) During/After Study Drug Administration   [ Time Frame: First dose of study drug to 30 days after final study visit for AEs and until resolution for SAEs ]

7.  Secondary:   Change in Potassium Level From Baseline in Lisinopril-naive Participants   [ Time Frame: At baseline visit and Day 14 prior to final study dose. ]

8.  Secondary:   Worse Post-dose Decrease in Estimated Glomerular Filtration Rate (eGFR) From Baseline in Lisinopril-naive Participants   [ Time Frame: Baseline to Day 14 (+/- 3 days) ]

9.  Secondary:   Largest eGFR Percent Decrease From Baseline in Lisinopril-naive Participants   [ Time Frame: Baseline to Day 14 (+/- 3 days) ]

10.  Secondary:   Change in Urine Protein/Creatinine From Baseline in Lisinopril-naive Participants.   [ Time Frame: Baseline to worst post-dose before Day 14 (+/- 3 days) ]

11.  Secondary:   Change in Diastolic Blood Pressure From Baseline in Lisinopril-naive Participants   [ Time Frame: Baseline to Day 14 (+/-3 days) ]

12.  Secondary:   Change in Systolic Blood Pressure From Baseline in Lisinopril-naive Participants   [ Time Frame: Baseline to Day 14 (+/- 3 days) ]

13.  Secondary:   Change in Systolic Blood Pressure (BP) From Baseline in Lisinopril SOC Group   [ Time Frame: Screening to Day 14 to 40 ]

14.  Secondary:   Change in Diastolic Blood Pressure From Baseline in Lisinopril SOC Group   [ Time Frame: Screening to Day 14 to 40 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Uptal Patel, MD
Organization: Duke Clinical Research Institute
phone: 919-668-4601
e-mail: uptal.patel@duke.edu


Publications:
Prinivil® (lisinopril tablets) package insert; Whitehouse Station, NJ: Merck & Co., Inc.; 2003
CDER Approval Package for Prinivil®: Application Number 19-558/S-043. Clinical Pharmacology and Biopharmaceutics Review. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/19-558S043_Prinivil.cfm. Last accessed Jan. 6, 2011.


Responsible Party: Uptal Patel, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT01491919     History of Changes
Other Study ID Numbers: Pro00029537, HHSN275201000003I
Study First Received: November 29, 2011
Results First Received: April 27, 2015
Last Updated: June 15, 2015
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
Best Pharmaceuticals for Children Act(BPCA): Data Monitoring Committee