Trial Outcomes & Findings for Safety Study of Lisinopril in Children and Adolescents With a Kidney Transplant (NCT NCT01491919)
NCT ID: NCT01491919
Last Updated: 2015-07-08
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
26 participants
Primary outcome timeframe
Day 14 (+/- 3 days) of lisinopril therapy at hours 0 (pre-dose) and 1,2,4,5,8,12 and 24 hrs after dose
Results posted on
2015-07-08
Participant Flow
Participant milestones
| Measure |
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.
|
|---|---|---|---|
|
Overall Study
STARTED
|
13
|
10
|
3
|
|
Overall Study
COMPLETED
|
12
|
8
|
2
|
|
Overall Study
NOT COMPLETED
|
1
|
2
|
1
|
Reasons for withdrawal
| Measure |
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.
|
|---|---|---|---|
|
Overall Study
Insufficient PK sampling
|
1
|
2
|
1
|
Baseline Characteristics
Safety Study of Lisinopril in Children and Adolescents With a Kidney Transplant
Baseline characteristics by cohort
| Measure |
Low Dose: Lisinopril
n=12 Participants
Participants will receive study medication for 14±3 days at a dose 0.1 mg/kg/day
|
Medium Dose: Lisinopril
n=8 Participants
Participants will receive study medication for 14±3 days at a dose 0.2 mg/kg/day
|
High Dose: Lisinopril
n=2 Participants
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
n=22 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
14.9 years
STANDARD_DEVIATION 2.3 • n=5 Participants
|
13.0 years
STANDARD_DEVIATION 3 • n=7 Participants
|
9.5 years
STANDARD_DEVIATION 3.5 • n=5 Participants
|
13.8 years
STANDARD_DEVIATION 3 • n=4 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
15 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
7 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
11 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
12 participants
n=5 Participants
|
8 participants
n=7 Participants
|
2 participants
n=5 Participants
|
22 participants
n=4 Participants
|
|
Estimated glomerular filtration rate (eGFR)
|
72.5 ml/min per 1.73m^2
STANDARD_DEVIATION 25.7 • n=5 Participants
|
62 ml/min per 1.73m^2
STANDARD_DEVIATION 16.7 • n=7 Participants
|
89.3 ml/min per 1.73m^2
STANDARD_DEVIATION 44.4 • n=5 Participants
|
70.2 ml/min per 1.73m^2
STANDARD_DEVIATION 24.4 • n=4 Participants
|
|
Time since transplant
|
4.8 years
STANDARD_DEVIATION 4.7 • n=5 Participants
|
4.9 years
STANDARD_DEVIATION 3.4 • n=7 Participants
|
0.9 years
STANDARD_DEVIATION 0.4 • n=5 Participants
|
4.5 years
STANDARD_DEVIATION 4.1 • n=4 Participants
|
|
Ethnicity
Hispanic/Latino
|
2 participants
n=5 Participants
|
2 participants
n=7 Participants
|
0 participants
n=5 Participants
|
4 participants
n=4 Participants
|
|
Ethnicity
Non-hispanic/non-latino
|
10 participants
n=5 Participants
|
6 participants
n=7 Participants
|
2 participants
n=5 Participants
|
18 participants
n=4 Participants
|
|
Weight
|
56.8 kg
STANDARD_DEVIATION 19.4 • n=5 Participants
|
50.2 kg
STANDARD_DEVIATION 28.7 • n=7 Participants
|
23.1 kg
STANDARD_DEVIATION 3.0 • n=5 Participants
|
51.3 kg
STANDARD_DEVIATION 23.8 • n=4 Participants
|
PRIMARY outcome
Timeframe: Day 14 (+/- 3 days) of lisinopril therapy at hours 0 (pre-dose) and 1,2,4,5,8,12 and 24 hrs after doseAt 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.
Outcome measures
| Measure |
High Dose: Lisinopril
n=2 Participants
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.
|
Low Dose: Lisinopril
n=12 Participants
Participants will receive study medication for 14±3 days at a dose 0.1 mg/kg/day
|
Medium Dose: Lisinopril
n=8 Participants
Participants will receive study medication for 14±3 days at a dose 0.2 mg/kg/day
|
|---|---|---|---|
|
Pharmacokinetics (PK) - Area Under the Plasma Concentration-time Curve (AUC)
|
702 ng*h/mL
Geometric Coefficient of Variation 66.4
|
298 ng*h/mL
Geometric Coefficient of Variation 46.5
|
640 ng*h/mL
Geometric Coefficient of Variation 28.6
|
PRIMARY outcome
Timeframe: Day14 (+/- 3 d) of dose at 0 hour and 1, 2, 4, 5, 8, 12, and 24 hrs after doseAt 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.
Outcome measures
| Measure |
High Dose: Lisinopril
n=2 Participants
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.
|
Low Dose: Lisinopril
n=12 Participants
Participants will receive study medication for 14±3 days at a dose 0.1 mg/kg/day
|
Medium Dose: Lisinopril
n=8 Participants
Participants will receive study medication for 14±3 days at a dose 0.2 mg/kg/day
|
|---|---|---|---|
|
PK - Maximum Observed Concentration of Drug in Plasma (Cmax)
|
58.0 ng/ml
Geometric Coefficient of Variation 41.2
|
20.9 ng/ml
Geometric Coefficient of Variation 41.2
|
47.7 ng/ml
Geometric Coefficient of Variation 25.1
|
PRIMARY outcome
Timeframe: Day 14 (+/- 3 d) of dose at 0 hour and 1, 2, 4, 5, 8, 12, and 24 hrs after doseAt 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.
Outcome measures
| Measure |
High Dose: Lisinopril
n=2 Participants
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.
|
Low Dose: Lisinopril
n=12 Participants
Participants will receive study medication for 14±3 days at a dose 0.1 mg/kg/day
|
Medium Dose: Lisinopril
n=8 Participants
Participants will receive study medication for 14±3 days at a dose 0.2 mg/kg/day
|
|---|---|---|---|
|
PK - Time of the Maximum Observed Concentration in Plasma (Tmax)
|
4.5 hours
Interval 4.0 to 5.0
|
5.0 hours
Interval 4.0 to 8.1
|
5.0 hours
Interval 4.0 to 8.0
|
PRIMARY outcome
Timeframe: Day 14 (+/- 3 d) of dose at 0 hour and at 1, 2, 4, 5, 8, 12, and 24 hrs after doseAt 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.
Outcome measures
| Measure |
High Dose: Lisinopril
n=2 Participants
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.
|
Low Dose: Lisinopril
n=12 Participants
Participants will receive study medication for 14±3 days at a dose 0.1 mg/kg/day
|
Medium Dose: Lisinopril
n=8 Participants
Participants will receive study medication for 14±3 days at a dose 0.2 mg/kg/day
|
|---|---|---|---|
|
PK - Oral Clearance (CL/F)
|
32.8 L/h/70 kg
Geometric Coefficient of Variation 54.1
|
17.9 L/h/70 kg
Geometric Coefficient of Variation 61.2
|
18.6 L/h/70 kg
Geometric Coefficient of Variation 34.4
|
PRIMARY outcome
Timeframe: 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.
Outcome measures
| Measure |
High Dose: Lisinopril
n=2 Participants
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.
|
Low Dose: Lisinopril
n=12 Participants
Participants will receive study medication for 14±3 days at a dose 0.1 mg/kg/day
|
Medium Dose: Lisinopril
n=8 Participants
Participants will receive study medication for 14±3 days at a dose 0.2 mg/kg/day
|
|---|---|---|---|
|
PK Renal Clearance (CLrenal)
|
6.8 L/h/70 kg
Geometric Coefficient of Variation 94.4
|
3.4 L/h/70 kg
Geometric Coefficient of Variation 60.4
|
3.4 L/h/70 kg
Geometric Coefficient of Variation 46.0
|
PRIMARY outcome
Timeframe: First dose of study drug to 30 days after final study visit for AEs and until resolution for SAEsNumber of Adverse Events (AEs) related and not related to study drug; number of Serious Adverse Events (SAEs) related and not related to study drug
Outcome measures
| Measure |
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.
|
Low Dose: Lisinopril
n=15 Participants
Participants will receive study medication for 14±3 days at a dose 0.1 mg/kg/day
|
Medium Dose: Lisinopril
n=11 Participants
Participants will receive study medication for 14±3 days at a dose 0.2 mg/kg/day
|
|---|---|---|---|
|
Number of Adverse Events (AEs) and Serious Adverse Events (SAEs) During/After Study Drug Administration
AEs
|
—
|
12 events
|
12 events
|
|
Number of Adverse Events (AEs) and Serious Adverse Events (SAEs) During/After Study Drug Administration
AE related to study drug
|
—
|
5 events
|
0 events
|
|
Number of Adverse Events (AEs) and Serious Adverse Events (SAEs) During/After Study Drug Administration
AEs not related to study drug
|
—
|
7 events
|
12 events
|
|
Number of Adverse Events (AEs) and Serious Adverse Events (SAEs) During/After Study Drug Administration
SAE
|
—
|
1 events
|
0 events
|
|
Number of Adverse Events (AEs) and Serious Adverse Events (SAEs) During/After Study Drug Administration
SAE not related to study drug
|
—
|
1 events
|
0 events
|
SECONDARY outcome
Timeframe: At baseline visit and Day 14 prior to final study dose.Potassium values will be obtained at Baseline and Day 14 prior to the final dose of study drug. Mean calculated from the two measurements.
Outcome measures
| Measure |
High Dose: Lisinopril
n=3 Participants
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.
|
Low Dose: Lisinopril
n=6 Participants
Participants will receive study medication for 14±3 days at a dose 0.1 mg/kg/day
|
Medium Dose: Lisinopril
n=6 Participants
Participants will receive study medication for 14±3 days at a dose 0.2 mg/kg/day
|
|---|---|---|---|
|
Change in Potassium Level From Baseline in Lisinopril-naive Participants
|
0.3 mEq/L
Standard Deviation 0.5
|
0.1 mEq/L
Standard Deviation 0.3
|
-0.3 mEq/L
Standard Deviation 0.6
|
SECONDARY outcome
Timeframe: Baseline to Day 14 (+/- 3 days)The eGFR at entry will need to be ≥ 30 ml/min/1.73m\^2 to minimize concerns about an acute angiotensin-converting enzyme inhibitors (ACE-I)-mediated reduction in kidney function. eGFR ratio was computed from the worst post-dose value divided by the Baseline value.
Outcome measures
| Measure |
High Dose: Lisinopril
n=3 Participants
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.
|
Low Dose: Lisinopril
n=6 Participants
Participants will receive study medication for 14±3 days at a dose 0.1 mg/kg/day
|
Medium Dose: Lisinopril
n=6 Participants
Participants will receive study medication for 14±3 days at a dose 0.2 mg/kg/day
|
|---|---|---|---|
|
Worse Post-dose Decrease in Estimated Glomerular Filtration Rate (eGFR) From Baseline in Lisinopril-naive Participants
|
0.89 ratio
Geometric Coefficient of Variation 14
|
1 ratio
Geometric Coefficient of Variation 14
|
1.02 ratio
Geometric Coefficient of Variation 10
|
SECONDARY outcome
Timeframe: Baseline to Day 14 (+/- 3 days)The eGFR at entry will need to be ≥ 30 ml/min/1.73m\^2 to minimize concerns about an acute angiotensin-converting enzyme inhibitor (ACEI) mediated reduction in kidney function. Largest eGFR percent decrease from baseline reported in results section.
Outcome measures
| Measure |
High Dose: Lisinopril
n=3 Participants
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.
|
Low Dose: Lisinopril
n=6 Participants
Participants will receive study medication for 14±3 days at a dose 0.1 mg/kg/day
|
Medium Dose: Lisinopril
n=6 Participants
Participants will receive study medication for 14±3 days at a dose 0.2 mg/kg/day
|
|---|---|---|---|
|
Largest eGFR Percent Decrease From Baseline in Lisinopril-naive Participants
|
21 percentage
|
15 percentage
|
12 percentage
|
SECONDARY outcome
Timeframe: Baseline to worst post-dose before Day 14 (+/- 3 days)Change in urine protein/creatinine obtained as follows: Mean change (worst post-dose from baseline) presented for urine protein/creatinine ratio. Geometric mean of the ratio (worst post-dose / baseline with Geometric Coefficient of Variation percent (CV%) and greatest decrease presented for eGFR by dose group. Two patients in the high dose group had an evaluable urine protein/creatinine change.
Outcome measures
| Measure |
High Dose: Lisinopril
n=3 Participants
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.
|
Low Dose: Lisinopril
n=6 Participants
Participants will receive study medication for 14±3 days at a dose 0.1 mg/kg/day
|
Medium Dose: Lisinopril
n=6 Participants
Participants will receive study medication for 14±3 days at a dose 0.2 mg/kg/day
|
|---|---|---|---|
|
Change in Urine Protein/Creatinine From Baseline in Lisinopril-naive Participants.
|
-0.74 mg/mg
Geometric Coefficient of Variation 1.37
|
-0.45 mg/mg
Geometric Coefficient of Variation 0.6
|
-0.08 mg/mg
Geometric Coefficient of Variation 0.15
|
SECONDARY outcome
Timeframe: Baseline to Day 14 (+/-3 days)Population: Change in diastolic blood pressure from baseline is reported here for lisinopril-naive participants (not the standard of care group which are reported separately).
Ambulatory blood pressure readings were measured during the baseline/pre-study dose period using a SpaceLabs (Redmond, WA) device at home to avoid the confounding effects of venipuncture and abnormal sleep pattern. Another blood pressure reading was performed at 1 day before the final dose of lisinopril (day before the last scheduled visit). The mean of these measurements was calculated.
Outcome measures
| Measure |
High Dose: Lisinopril
n=3 Participants
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.
|
Low Dose: Lisinopril
n=6 Participants
Participants will receive study medication for 14±3 days at a dose 0.1 mg/kg/day
|
Medium Dose: Lisinopril
n=6 Participants
Participants will receive study medication for 14±3 days at a dose 0.2 mg/kg/day
|
|---|---|---|---|
|
Change in Diastolic Blood Pressure From Baseline in Lisinopril-naive Participants
eGFR 30-59 ml/min per 1.73m^2 (n=3, 1, 0)
|
NA mmHg
Standard Deviation NA
no participants in this category
|
-4.0 mmHg
Standard Deviation 20
|
7.0 mmHg
Standard Deviation 0
|
|
Change in Diastolic Blood Pressure From Baseline in Lisinopril-naive Participants
eGFR >=60 ml/min per 1.73m^2 (n=3, 5, 3)
|
-4.0 mmHg
Standard Deviation 5.3
|
-9.0 mmHg
Standard Deviation 7.5
|
-6.0 mmHg
Standard Deviation 6.7
|
SECONDARY outcome
Timeframe: Baseline to Day 14 (+/- 3 days)Population: Change in systolic blood pressure from baseline is reported here for lisinopril-naive participants (not the standard of care (SOC) group which are reported separately).
Ambulatory blood pressure readings were measured during the baseline/pre-study dose period using a SpaceLabs (Redmond, WA) device at home to avoid the confounding effects of venipuncture and abnormal sleep pattern. Another blood pressure reading was performed at 1 day before the final dose of lisinopril (day before the last scheduled visit). The mean from these measurements was calculated.
Outcome measures
| Measure |
High Dose: Lisinopril
n=3 Participants
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.
|
Low Dose: Lisinopril
n=6 Participants
Participants will receive study medication for 14±3 days at a dose 0.1 mg/kg/day
|
Medium Dose: Lisinopril
n=6 Participants
Participants will receive study medication for 14±3 days at a dose 0.2 mg/kg/day
|
|---|---|---|---|
|
Change in Systolic Blood Pressure From Baseline in Lisinopril-naive Participants
eGFR 30-59 ml/min per 1.73m2 (n=3, 1, 0)
|
NA mmHg
Standard Deviation NA
no participants in this category
|
-5.0 mmHg
Standard Deviation 11.4
|
-6.0 mmHg
Standard Deviation 0
|
|
Change in Systolic Blood Pressure From Baseline in Lisinopril-naive Participants
eGFR >+60 ml/min per 1.732 (n=3, 5, 3)
|
-11.3 mmHg
Standard Deviation 2.1
|
-6.7 mmHg
Standard Deviation 4.0
|
-8.8 mmHg
Standard Deviation 11.7
|
SECONDARY outcome
Timeframe: Screening to Day 14 to 40Population: Change in systolic blood pressure from baseline is reported here for lisinopril SOCparticipants (not the Lisinopril-naive group which are reported separately).
Lisinopril SOC participants were not given the ambulatory blood pressure machine to obtain readings at home, as was the Lisinopril-naive participants. Instead BP measurements were obtained during screening visit and compared to the Day 14 to 40 visit measurements. Note: these participants were not required to attend a Day 14 (+/-3 day visit) but did need to attend sometime between Day 14 to Day 40 (inclusive). The mean of these blood pressure measurements was calculated.
Outcome measures
| Measure |
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.
|
Low Dose: Lisinopril
n=7 Participants
Participants will receive study medication for 14±3 days at a dose 0.1 mg/kg/day
|
Medium Dose: Lisinopril
n=4 Participants
Participants will receive study medication for 14±3 days at a dose 0.2 mg/kg/day
|
|---|---|---|---|
|
Change in Systolic Blood Pressure (BP) From Baseline in Lisinopril SOC Group
eGFR 30-59 ml/min per 1.73m2 (n=2, 2, 0)
|
—
|
-6.0 mmHg
Standard Deviation 17
|
-1.0 mmHg
Standard Deviation 4.2
|
|
Change in Systolic Blood Pressure (BP) From Baseline in Lisinopril SOC Group
eGFR >=60 ml/min per 1.73m2 (n=5, 2, 0)
|
—
|
6.4 mmHg
Standard Deviation 6.9
|
-1.0 mmHg
Standard Deviation 0
|
SECONDARY outcome
Timeframe: Screening to Day 14 to 40Population: Change in diastolic blood pressure from baseline is reported here for lisinopril SOCparticipants (not the Lisinopril-naive group which are reported separately).
Lisinopril SOC participants were not given the ambulatory blood pressure machine to obtain readings at home, as was the Lisinopril-naive participants. Instead BP measurements were obtained during screening visit and compared to the Day 14 to 40 visit measurements (note: the participants were not required to attend a Day 14 (+/-3 day visit) but did need to attend sometime between Day 14 to Day 40. The mean from the blood pressure measurements was calculated.
Outcome measures
| Measure |
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.
|
Low Dose: Lisinopril
n=7 Participants
Participants will receive study medication for 14±3 days at a dose 0.1 mg/kg/day
|
Medium Dose: Lisinopril
n=4 Participants
Participants will receive study medication for 14±3 days at a dose 0.2 mg/kg/day
|
|---|---|---|---|
|
Change in Diastolic Blood Pressure From Baseline in Lisinopril SOC Group
eGFR 30-59 ml/min per 1.73m2 (n=2, 2, 0)
|
—
|
-6.0 mmHg
Standard Deviation 5.7
|
-6.5 mmHg
Standard Deviation 9.2
|
|
Change in Diastolic Blood Pressure From Baseline in Lisinopril SOC Group
eGFR >=60 ml/min per 1.73m2 (n=5, 2, 0)
|
—
|
3.4 mmHg
Standard Deviation 14.0
|
-3.0 mmHg
Standard Deviation 0
|
Adverse Events
Low Dose: Lisinopril
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Medium Dose: Lisinopril
Serious events: 1 serious events
Other events: 4 other events
Deaths: 0 deaths
High Dose: Lisinopril
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Low Dose: Lisinopril
n=12 participants at risk
Participants will receive study medication for 14±3 days at a dose 0.1 mg/kg/day
|
Medium Dose: Lisinopril
n=8 participants at risk
Participants will receive study medication for 14±3 days at a dose 0.2 mg/kg/day
|
High Dose: Lisinopril
n=2 participants at risk
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.
|
|---|---|---|---|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/12
|
12.5%
1/8
|
0.00%
0/2
|
Other adverse events
| Measure |
Low Dose: Lisinopril
n=12 participants at risk
Participants will receive study medication for 14±3 days at a dose 0.1 mg/kg/day
|
Medium Dose: Lisinopril
n=8 participants at risk
Participants will receive study medication for 14±3 days at a dose 0.2 mg/kg/day
|
High Dose: Lisinopril
n=2 participants at risk
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.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
8.3%
1/12
|
0.00%
0/8
|
0.00%
0/2
|
|
Gastrointestinal disorders
Abdominal pain upper
|
8.3%
1/12
|
25.0%
2/8
|
0.00%
0/2
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/12
|
25.0%
2/8
|
0.00%
0/2
|
|
Gastrointestinal disorders
Nausea
|
8.3%
1/12
|
12.5%
1/8
|
0.00%
0/2
|
|
Gastrointestinal disorders
Retching
|
0.00%
0/12
|
25.0%
2/8
|
0.00%
0/2
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/12
|
0.00%
0/8
|
50.0%
1/2
|
|
General disorders
Infusion site extravasation
|
8.3%
1/12
|
0.00%
0/8
|
0.00%
0/2
|
|
General disorders
Infusion site pain
|
8.3%
1/12
|
0.00%
0/8
|
0.00%
0/2
|
|
General disorders
Infusion site pruritus
|
8.3%
1/12
|
0.00%
0/8
|
0.00%
0/2
|
|
Infections and infestations
Otitis externa
|
0.00%
0/12
|
12.5%
1/8
|
0.00%
0/2
|
|
Injury, poisoning and procedural complications
Upper limb fracture
|
0.00%
0/12
|
0.00%
0/8
|
50.0%
1/2
|
|
Investigations
Glomerular filtration rate decreased
|
0.00%
0/12
|
0.00%
0/8
|
50.0%
1/2
|
|
Investigations
Hemoglobin decreased
|
0.00%
0/12
|
0.00%
0/8
|
50.0%
1/2
|
|
Nervous system disorders
Dizziness
|
0.00%
0/12
|
25.0%
2/8
|
0.00%
0/2
|
|
Nervous system disorders
Headache
|
8.3%
1/12
|
12.5%
1/8
|
0.00%
0/2
|
|
Skin and subcutaneous tissue disorders
Rash
|
8.3%
1/12
|
0.00%
0/8
|
0.00%
0/2
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place