Clinical Trial Results:
An open label extentsion study to evaluate safety, tolerability, and efficacy of 18 weeks of valsartan treatment in children 6 months -5 years old with hypertension
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Summary
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EudraCT number |
2006-005473-21 |
Trial protocol |
BE FR GB HU SE IT DE |
Global end of trial date |
25 May 2009
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Results information
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Results version number |
v2(current) |
This version publication date |
17 Sep 2021
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First version publication date |
30 Jul 2015
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Other versions |
v1 |
Version creation reason |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
CVAL489K2303E1
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00457626 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Novartis Pharma AG
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Sponsor organisation address |
CH-4002, Basel, Switzerland,
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Public contact |
Clinical Disclosure Office, Novartis Pharma AG, +41 613241111,
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Scientific contact |
Clinical Disclosure Office, Novartis Pharma AG, +41 613241111,
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
25 May 2009
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
25 May 2009
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The main objective of the study was to evaluate the efficacy, safety and tolerability of long-term use of valsartan (1milligram/kilogram [mg/kg] or 2 mg/kg or 4 mg/kg) in hypertensive children aged 6 months to 5 years.
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
09 Apr 2007
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 4
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Country: Number of subjects enrolled |
South Africa: 5
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Country: Number of subjects enrolled |
Turkey: 2
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Country: Number of subjects enrolled |
Brazil: 8
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Country: Number of subjects enrolled |
India: 19
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Country: Number of subjects enrolled |
Poland: 10
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Country: Number of subjects enrolled |
France: 3
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Country: Number of subjects enrolled |
Hungary: 3
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Country: Number of subjects enrolled |
Italy: 2
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Country: Number of subjects enrolled |
Belgium: 10
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Worldwide total number of subjects |
66
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EEA total number of subjects |
28
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
10
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Children (2-11 years) |
56
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was conducted at 35 centres in 10 countries. | ||||||||||||||
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Pre-assignment
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Screening details |
This study enrolled a total of 66 subjects who completed the core study (CVAL489K2303). | ||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||
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Arms
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Arm title
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Valsartan | ||||||||||||||
Arm description |
Extemporaneous oral suspension prepared from valsartan tablets was administered to subjects once daily. The starting dose of valsartan was 1mg/kg which was escalated to 2 mg/kg or 4 mg/kg based on systolic blood pressure control after 2 weeks. | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
Valsartan
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Investigational medicinal product code |
VAL489
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Other name |
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Pharmaceutical forms |
Oral suspension
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Routes of administration |
Oral use
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Dosage and administration details |
Extemporaneous oral suspension prepared from valsartan tablets was administered to subjects once daily. The starting dose of valsartan was 1mg/kg which was escalated to 2 mg/kg or 4 mg/kg based on systolic blood pressure control after 2 weeks.
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Baseline characteristics reporting groups
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Reporting group title |
Overall Study
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Valsartan
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Reporting group description |
Extemporaneous oral suspension prepared from valsartan tablets was administered to subjects once daily. The starting dose of valsartan was 1mg/kg which was escalated to 2 mg/kg or 4 mg/kg based on systolic blood pressure control after 2 weeks. | ||
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End point title |
Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 26 [1] | ||||||||
End point description |
Sitting blood pressure was measured using a calibrated standard sphygmomanometer after the subject remained in sitting position for 5 minutes at clinic during the visit. The repeat sitting measurements were made at 1-2 minute intervals and the mean of three sitting systolic blood pressure (SSBP) measurements were used as the average sitting office blood pressure for that visit. The analysis was performed on Extension set, which included all subjects who entered open-label extension period with administration of at least one dose of open-label study drug. Missing data was imputed using last observation carry forward (LOCF) technique.
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End point type |
Primary
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End point timeframe |
Baseline to Week 26
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses have been reported for this primary end point. |
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End point title |
Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 26 [2] | ||||||||
End point description |
Sitting blood pressure was measured using a calibrated standard sphygmomanometer after the subject remained in sitting position for 5 minutes at clinic during the visit. The repeat sitting measurements were made at 1-2 minute intervals and the mean of three SDBP measurements were used as the average sitting office blood pressure for that visit. The analysis was performed on Extension set. Missing data was imputed using LOCF technique.
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End point type |
Primary
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End point timeframe |
Baseline to Week 26
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses have been reported for this primary end point. |
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End point title |
Number of subjects with Adverse Events (AEs) and Serious Adverse Events (SAEs) [3] | ||||||||||
End point description |
An AE was defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not related to study drug. A SAE was defined as an event which was fatal or life threatening, required or prolonged hospitalization, was significantly or permanently disabling or incapacitating, constituted a congenital anomaly or a birth defect, or encompassed any other clinically significant event that could jeopardize the subject or require medical or surgical intervention to prevent one of the aforementioned outcomes. The analysis was performed on Extension set.
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End point type |
Primary
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End point timeframe |
From Week 8 to Week 26 of extension phase
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses have been reported for this primary end point. |
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
12
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Reporting groups
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Reporting group title |
Valsartan
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Reporting group description |
Extemporaneous oral suspension prepared from valsartan tablets was administered to subjects once daily. The starting dose of valsartan was 1mg/kg which was escalated to 2 mg/kg or 4 mg/kg based on systolic blood pressure control after 2 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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26 Jun 2007 |
• A statement was added that unscheduled visits could be performed as needed at the discretion of the investigator to monitor patient safety.
• Two exclusion criteria were added: Patients who experienced any AEs considered serious or drug related in the core study and patients excluded from the core study.
• Details regarding study medication (including the supply, administration and preparation of the suspension) were added.
• Specifics regarding the use of concomitant medication were added.
• Instructions regarding study drug discontinuation, formerly missing from the protocol, were added.
• Urine dipstick testing was added.
• The requirement for patients to be fasting prior to laboratory evaluations was removed.
• Details on the collection and reporting of Suspected Unexpected Serious Adverse Reactions (SUSARs) were added, in accordance with Directive 2001/20/EC or as per
national regulatory requirements in participating countries.
• GFR testing (Glomerular Filtration Rate) was added.
• Several values in the tables of BP levels by age and height percentile were inaccurate. The tables (located in Appendix 3 of the protocol) were replaced to reflect correct values.
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30 Sep 2008 |
• The age range of the study subjects was changed from 1 to 5 years old to 6 months to 5 years old as per recommendations from European Medicines Agency Pediatric Committee
• Several changes were made to the section on discontinuation of study drug. These enhanced the monitoring of liver function, renal function and serum potassium alerts in all patients.
• Instructions were also added regarding decreases in body weight.
• The timing of visits was revised: all extension visits were conducted in relation to the number of days from Day 0, instead of the previous extension visit.
• The section on GFR estimates was revised to include infants <1 year old. The 2 to 12 year age group was changed to 1 to 12 years.
• Revisions were made to include the recommendations of an independent External Safety Monitoring Committee (ESMC).
• Blood-pressure charts for children 6 months to <1 year old were added to Appendix 3 of the protocol.
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
