Trial Outcomes & Findings for A Study to Evaluate the Safety/Tolerability and Pharmacokinetics of Aliskiren in Hypertensive Pediatric and Adolescent Patients 6-17 Years of Age (NCT NCT00834041)
NCT ID: NCT00834041
Last Updated: 2011-05-09
Results Overview
Blood samples (1 mL) for pharmacokinetic (PK) evaluation were drawn pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 10, and 24 hours following administration of aliskiren on Day 1 and Day 8. The pre-dose PK evaluations were collected in a fasted state (7-12 hours without food or beverage except water). PK parameters were calculated from plasma concentration-time data and actual recorded sampling times for each patient, using non-compartmental methods with the software program WinNonlin Pro v5.2.
COMPLETED
PHASE1/PHASE2
39 participants
Day 1 and Day 8
2011-05-09
Participant Flow
Participant milestones
| Measure |
Aliskiren 2 mg/kg
Patients received aliskiren 2 mg/kg of their body weight orally once daily at approximately 8 AM.
|
Aliskiren 6 mg/kg
Patients received aliskiren 6 mg/kg of their body weight orally once daily at approximately 8 AM.
|
|---|---|---|
|
Overall Study
STARTED
|
19
|
20
|
|
Overall Study
COMPLETED
|
18
|
19
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
Reasons for withdrawal
| Measure |
Aliskiren 2 mg/kg
Patients received aliskiren 2 mg/kg of their body weight orally once daily at approximately 8 AM.
|
Aliskiren 6 mg/kg
Patients received aliskiren 6 mg/kg of their body weight orally once daily at approximately 8 AM.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
Baseline Characteristics
A Study to Evaluate the Safety/Tolerability and Pharmacokinetics of Aliskiren in Hypertensive Pediatric and Adolescent Patients 6-17 Years of Age
Baseline characteristics by cohort
| Measure |
Aliskiren 2 mg/kg
n=19 Participants
Patients received aliskiren 2 mg/kg of their body weight orally once daily at approximately 8 AM.
|
Aliskiren 6 mg/kg
n=20 Participants
Patients received aliskiren 6 mg/kg of their body weight orally once daily at approximately 8 AM.
|
Total
n=39 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
12.2 years
STANDARD_DEVIATION 3.12 • n=99 Participants
|
11.8 years
STANDARD_DEVIATION 3.78 • n=107 Participants
|
12.0 years
STANDARD_DEVIATION 3.44 • n=206 Participants
|
|
Age, Customized
6-11 years old
|
10 participants
n=99 Participants
|
10 participants
n=107 Participants
|
20 participants
n=206 Participants
|
|
Age, Customized
12-17 years old
|
9 participants
n=99 Participants
|
10 participants
n=107 Participants
|
19 participants
n=206 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
18 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=99 Participants
|
12 Participants
n=107 Participants
|
21 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Day 1 and Day 8Population: Pharmacokinetic population: All patients who had evaluable aliskiren concentration data.
Blood samples (1 mL) for pharmacokinetic (PK) evaluation were drawn pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 10, and 24 hours following administration of aliskiren on Day 1 and Day 8. The pre-dose PK evaluations were collected in a fasted state (7-12 hours without food or beverage except water). PK parameters were calculated from plasma concentration-time data and actual recorded sampling times for each patient, using non-compartmental methods with the software program WinNonlin Pro v5.2.
Outcome measures
| Measure |
Aliskiren 2 mg/kg
n=19 Participants
Patients received aliskiren 2 mg/kg of their body weight orally once daily at approximately 8 AM.
|
Aliskiren 6 mg/kg
n=20 Participants
Patients received aliskiren 6 mg/kg of their body weight orally once daily at approximately 8 AM.
|
|---|---|---|
|
Maximum Plasma Concentration (Cmax) at Day 1 and Day 8 in 6-11 and 12-17 Year Old Patients
Day 1: 6-11 years old, n=10, 10
|
76.8 ng/ml
Standard Deviation 78.21
|
393.3 ng/ml
Standard Deviation 377.37
|
|
Maximum Plasma Concentration (Cmax) at Day 1 and Day 8 in 6-11 and 12-17 Year Old Patients
Day 8: 6-11 years old, n=9, 10
|
82.2 ng/ml
Standard Deviation 97.85
|
397.1 ng/ml
Standard Deviation 187.06
|
|
Maximum Plasma Concentration (Cmax) at Day 1 and Day 8 in 6-11 and 12-17 Year Old Patients
Day 1: 12-17 years old, n=9, 10
|
136.5 ng/ml
Standard Deviation 132.57
|
424.3 ng/ml
Standard Deviation 188.79
|
|
Maximum Plasma Concentration (Cmax) at Day 1 and Day 8 in 6-11 and 12-17 Year Old Patients
Day 8: 12-17 years old, n=9, 10
|
278.7 ng/ml
Standard Deviation 357.54
|
485.7 ng/ml
Standard Deviation 300.58
|
PRIMARY outcome
Timeframe: Day 1 and Day 8Population: Pharmacokinetic population: All patients who had evaluable aliskiren concentration data.
Blood samples (1 mL) for pharmacokinetic (PK) evaluation were drawn pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 10, and 24 hours following administration of aliskiren on Day 1 and Day 8. The pre-dose PK evaluations were collected in a fasted state (7-12 hours without food or beverage except water). PK parameters were calculated from plasma concentration-time data and actual recorded sampling times for each patient, using non-compartmental methods with the software program WinNonlin Pro v5.2.
Outcome measures
| Measure |
Aliskiren 2 mg/kg
n=19 Participants
Patients received aliskiren 2 mg/kg of their body weight orally once daily at approximately 8 AM.
|
Aliskiren 6 mg/kg
n=20 Participants
Patients received aliskiren 6 mg/kg of their body weight orally once daily at approximately 8 AM.
|
|---|---|---|
|
Area Under the Plasma Concentration-time Curve (AUC0-τ) in One Dosing Interval (24 h) at Day 1 and Day 8 in 6-11 and 12-17 Year Old Patients
Day 1: 6-11 years old, n=10, 10
|
278.3 h*ng/mL
Standard Deviation 237.29
|
1231.0 h*ng/mL
Standard Deviation 728.46
|
|
Area Under the Plasma Concentration-time Curve (AUC0-τ) in One Dosing Interval (24 h) at Day 1 and Day 8 in 6-11 and 12-17 Year Old Patients
Day 8: 6-11 years old, n=9, 10
|
403.6 h*ng/mL
Standard Deviation 326.76
|
1959.9 h*ng/mL
Standard Deviation 821.43
|
|
Area Under the Plasma Concentration-time Curve (AUC0-τ) in One Dosing Interval (24 h) at Day 1 and Day 8 in 6-11 and 12-17 Year Old Patients
Day 1: 12-17 years old, n=9, 10
|
390.9 h*ng/mL
Standard Deviation 264.50
|
1808.7 h*ng/mL
Standard Deviation 806.78
|
|
Area Under the Plasma Concentration-time Curve (AUC0-τ) in One Dosing Interval (24 h) at Day 1 and Day 8 in 6-11 and 12-17 Year Old Patients
Day 8: 12-17 years old, n=9, 10
|
847.2 h*ng/mL
Standard Deviation 803.44
|
2087.0 h*ng/mL
Standard Deviation 999.10
|
PRIMARY outcome
Timeframe: Day 8Population: Pharmacokinetic population: All patients who had evaluable aliskiren concentration data.
Blood samples (1 mL) for pharmacokinetic (PK) evaluation were drawn pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 10, and 24 hours following administration of aliskiren on Day 1 and Day 8. The pre-dose PK evaluations were collected in a fasted state (7-12 hours without food or beverage except water). PK parameters were calculated from plasma concentration-time data and actual recorded sampling times for each patient, using non-compartmental methods with the software program WinNonlin Pro v5.2.
Outcome measures
| Measure |
Aliskiren 2 mg/kg
n=19 Participants
Patients received aliskiren 2 mg/kg of their body weight orally once daily at approximately 8 AM.
|
Aliskiren 6 mg/kg
n=20 Participants
Patients received aliskiren 6 mg/kg of their body weight orally once daily at approximately 8 AM.
|
|---|---|---|
|
Apparent Plasma Clearance (CL/F) at Day 8 in 6-11 and 12-17 Year Old Patients
Day 8: 6-11 years old, n=9, 10
|
9694.0 mL/h/kg
Standard Deviation 8704.71
|
3905.4 mL/h/kg
Standard Deviation 2628.52
|
|
Apparent Plasma Clearance (CL/F) at Day 8 in 6-11 and 12-17 Year Old Patients
Day 8: 12-17 years old, n=9, 10
|
5388.1 mL/h/kg
Standard Deviation 5580.55
|
3539.0 mL/h/kg
Standard Deviation 1587.49
|
SECONDARY outcome
Timeframe: Baseline to 2 and 10 hours post-dose on Day 1; pre-dose, 2, 10, and 24 hours post-dose on Day 8-9Population: Full Analysis Set (FAS): All randomized patients, excluding mis-randomized patients. Data was not available for all patients at all time points. For each time point, n = the number of subjects for whom data was available for each treatment group.
Blood samples (2 mL) for pharmacodynamics evaluation of plasma renin activity were drawn pre-dose and at 2 and 10 hours following the dose of study medication on Day 1 and at pre-dose and at 2, 10, and 24 hours post-dose on Day 8-9.
Outcome measures
| Measure |
Aliskiren 2 mg/kg
n=19 Participants
Patients received aliskiren 2 mg/kg of their body weight orally once daily at approximately 8 AM.
|
Aliskiren 6 mg/kg
n=20 Participants
Patients received aliskiren 6 mg/kg of their body weight orally once daily at approximately 8 AM.
|
|---|---|---|
|
Change in Plasma Renin Activity From Baseline on Day 1, Day 8, and Day 9
Day 1: 2 h post-dose, n=15, 15
|
-1.8 ng/mL/h
Standard Deviation 1.62
|
-4.0 ng/mL/h
Standard Deviation 6.68
|
|
Change in Plasma Renin Activity From Baseline on Day 1, Day 8, and Day 9
Day 1: 10 h post-dose, n=14, 13
|
-1.8 ng/mL/h
Standard Deviation 1.73
|
-3.8 ng/mL/h
Standard Deviation 6.79
|
|
Change in Plasma Renin Activity From Baseline on Day 1, Day 8, and Day 9
Day 8: pre-dose, n=14, 15
|
-1.3 ng/mL/h
Standard Deviation 1.77
|
-3.5 ng/mL/h
Standard Deviation 5.91
|
|
Change in Plasma Renin Activity From Baseline on Day 1, Day 8, and Day 9
Day 8: 2 h post-dose, n=11, 14
|
-1.4 ng/mL/h
Standard Deviation 1.60
|
-3.6 ng/mL/h
Standard Deviation 6.79
|
|
Change in Plasma Renin Activity From Baseline on Day 1, Day 8, and Day 9
Day 8: 10 h post dose, n=13, 15
|
-1.7 ng/mL/h
Standard Deviation 1.81
|
-3.8 ng/mL/h
Standard Deviation 6.41
|
|
Change in Plasma Renin Activity From Baseline on Day 1, Day 8, and Day 9
Day 8-9: 24 h post dose, n=13, 15
|
-1.5 ng/mL/h
Standard Deviation 1.82
|
-3.6 ng/mL/h
Standard Deviation 6.46
|
SECONDARY outcome
Timeframe: Baseline to end of treatment (Day 9)Population: Full Analysis Set (FAS): All randomized patients, excluding mis-randomized patients.
Blood pressure (BP) measurements were made with a mercury sphygmomanometer or an automated blood pressure measuring device. Sitting BP was measured 3 times at 2-3 minute intervals after the patient had been sitting for 5 minutes. Means of the 3 measurements were calculated. A negative change in BP indicates lowered BP.
Outcome measures
| Measure |
Aliskiren 2 mg/kg
n=19 Participants
Patients received aliskiren 2 mg/kg of their body weight orally once daily at approximately 8 AM.
|
Aliskiren 6 mg/kg
n=20 Participants
Patients received aliskiren 6 mg/kg of their body weight orally once daily at approximately 8 AM.
|
|---|---|---|
|
Change in Mean Sitting Systolic and Diastolic Blood Pressure (msSBP and msDBP) From Baseline to the End of Treatment (Day 9) in 6-11 and 12-17 Year Old Patients
msDBP: 6-11 years old, n=10, 10
|
-1.7 mmHg
Standard Deviation 4.69
|
0.0 mmHg
Standard Deviation 8.87
|
|
Change in Mean Sitting Systolic and Diastolic Blood Pressure (msSBP and msDBP) From Baseline to the End of Treatment (Day 9) in 6-11 and 12-17 Year Old Patients
msSBP: 6-11 years old, n=10, 10
|
-4.5 mmHg
Standard Deviation 14.63
|
-7.7 mmHg
Standard Deviation 11.76
|
|
Change in Mean Sitting Systolic and Diastolic Blood Pressure (msSBP and msDBP) From Baseline to the End of Treatment (Day 9) in 6-11 and 12-17 Year Old Patients
msSBP: 12-17 years old,n=9, 10
|
-7.6 mmHg
Standard Deviation 9.07
|
-7.7 mmHg
Standard Deviation 9.38
|
|
Change in Mean Sitting Systolic and Diastolic Blood Pressure (msSBP and msDBP) From Baseline to the End of Treatment (Day 9) in 6-11 and 12-17 Year Old Patients
msDBP: 12-17 years old, n=9, 10
|
-5.3 mmHg
Standard Deviation 8.78
|
-5.8 mmHg
Standard Deviation 8.00
|
Adverse Events
Aliskiren 2 mg/kg
Aliskiren 6 mg/kg
Serious adverse events
| Measure |
Aliskiren 2 mg/kg
n=19 participants at risk
Patients received aliskiren 2 mg/kg of their body weight orally once daily at approximately 8 AM.
|
Aliskiren 6 mg/kg
n=20 participants at risk
Patients received aliskiren 6 mg/kg of their body weight orally once daily at approximately 8 AM.
|
|---|---|---|
|
Infections and infestations
Swine influenza
|
0.00%
0/19 • 12 days
|
5.0%
1/20 • 12 days
|
Other adverse events
| Measure |
Aliskiren 2 mg/kg
n=19 participants at risk
Patients received aliskiren 2 mg/kg of their body weight orally once daily at approximately 8 AM.
|
Aliskiren 6 mg/kg
n=20 participants at risk
Patients received aliskiren 6 mg/kg of their body weight orally once daily at approximately 8 AM.
|
|---|---|---|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
0.00%
0/19 • 12 days
|
5.0%
1/20 • 12 days
|
|
Ear and labyrinth disorders
Tinnitus
|
5.3%
1/19 • 12 days
|
0.00%
0/20 • 12 days
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/19 • 12 days
|
5.0%
1/20 • 12 days
|
|
Gastrointestinal disorders
Abdominal pain upper
|
5.3%
1/19 • 12 days
|
10.0%
2/20 • 12 days
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/19 • 12 days
|
5.0%
1/20 • 12 days
|
|
Gastrointestinal disorders
Nausea
|
5.3%
1/19 • 12 days
|
10.0%
2/20 • 12 days
|
|
General disorders
Fatigue
|
5.3%
1/19 • 12 days
|
0.00%
0/20 • 12 days
|
|
General disorders
Pyrexia
|
0.00%
0/19 • 12 days
|
5.0%
1/20 • 12 days
|
|
Infections and infestations
Nasopharyngitis
|
5.3%
1/19 • 12 days
|
0.00%
0/20 • 12 days
|
|
Infections and infestations
Upper respiratory tract infection
|
5.3%
1/19 • 12 days
|
0.00%
0/20 • 12 days
|
|
Investigations
Blood pressure increased
|
5.3%
1/19 • 12 days
|
0.00%
0/20 • 12 days
|
|
Investigations
Body temperature increased
|
5.3%
1/19 • 12 days
|
0.00%
0/20 • 12 days
|
|
Nervous system disorders
Headache
|
21.1%
4/19 • 12 days
|
10.0%
2/20 • 12 days
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.3%
1/19 • 12 days
|
5.0%
1/20 • 12 days
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
5.3%
1/19 • 12 days
|
0.00%
0/20 • 12 days
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngeal inflammation
|
5.3%
1/19 • 12 days
|
0.00%
0/20 • 12 days
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
5.3%
1/19 • 12 days
|
0.00%
0/20 • 12 days
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.00%
0/19 • 12 days
|
5.0%
1/20 • 12 days
|
|
Vascular disorders
Flushing
|
0.00%
0/19 • 12 days
|
5.0%
1/20 • 12 days
|
|
Vascular disorders
Hypertension
|
0.00%
0/19 • 12 days
|
5.0%
1/20 • 12 days
|
Additional Information
Study Director
Novartis Pharmaceuticals
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
- Publication restrictions are in place
Restriction type: OTHER