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Efficacy, Safety and Tolerability of Multiple Doses of Valsartan in Children With Hypertension With or Without CKD

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01617681
First received: June 6, 2012
Last updated: October 6, 2014
Last verified: October 2014
  Purpose

To assess efficacy, safety and tolerability of valsartan when comparing two doses of valsartan in reducing and controlling blood pressure in children with hypertension with or without CKD.


Condition Intervention Phase
Pediatric Hypertension With or Without CKD
Drug: VAL489
Drug: VAL489 matching placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A 6 Week, Randomized, Multicenter, Double-blind, Double-dummy Study to Evaluate the Dose Response of Valsartan on Blood Pressure Reduction in Children 1-5 Years Old With Hypertension, With or Without Chronic Kidney Disease, Followed by a 20 Week Open-label Titration Phase

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Change from baseline (Week 0) in mean systolic blood pressure (MSBP) at Week 6 endpoint [ Time Frame: Baseline, week 6 ] [ Designated as safety issue: No ]
    Patient's blood pressure will be measured in the same position at every visit Systolic and diastolic blood pressures will be measured three times at 2-3 minute intervals. The arithmetic mean of these three blood pressure measurements will be used as the mean office blood pressure (MSBP and MDBP) for that visit.


Secondary Outcome Measures:
  • Change from baseline in mean diastolic blood pressure (MDBP) at Week 6 and end of study (26 weeks) [ Time Frame: 6 weeks, 26 weeks ] [ Designated as safety issue: Yes ]
    Patient's blood pressure will be measured in the same position at every visit Systolic and diastolic blood pressures will be measured three times at 2-3 minute intervals. The arithmetic mean of these three blood pressure measurements will be used as the mean office blood pressure (MSBP and MDBP) for that visit.

  • Percentage of patients achieving MSBP < 90th percentile for age, gender and height at Week 6 endpoint and end of study (26 weeks) [ Time Frame: 6 weeks, 26 weeks ] [ Designated as safety issue: Yes ]
    Patient's blood pressure will be measured in the same position at every visit Systolic and diastolic blood pressures will be measured three times at 2-3 minute intervals. The arithmetic mean of these three blood pressure measurements will be used as the mean office blood pressure (MSBP and MDBP) for that visit.

  • Number of patients with Urine Albumin Creatinine Ratio (UACR) response at Week 6 endpoint and end of study (26 weeks) [ Time Frame: 6 weeks, 26 weeks ] [ Designated as safety issue: Yes ]
    UACR response is defined as percentage change from baseline in UACR≤ 25%. UACR [mg/mmol] = urine albumin [mg/L] / urine creatinine [mmol/L]

  • Number of patients with adverse events, serious adverse events and death [ Time Frame: 26 weeks ] [ Designated as safety issue: Yes ]
    Patients safety will be based on frequency of adverse events.


Estimated Enrollment: 130
Study Start Date: November 2012
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Valsartan 0.25 mg/kg
Valsartan oral solution 0.25mg/kg once daily + matching placebo of valsartan oral solution 4 mg/kg once daily for 6 weeks (period 1)
Drug: VAL489
Valsartan 3mg/kg oral solution
Other Name: Diovan
Drug: VAL489 matching placebo
Valsartan 3 mg/kg oral solution
Other Name: Diovan
Experimental: Valsartan 4 mg/kg
Valsartan oral solution 4 mg/kg once daily + matching placebo of valsartan oral solution 0.25 mg/kg once daily for 6 weeks (period 1)
Drug: VAL489
Valsartan 3mg/kg oral solution
Other Name: Diovan
Drug: VAL489 matching placebo
Valsartan 3 mg/kg oral solution
Other Name: Diovan
Experimental: Valsartan 1 mg/kg
Open-label (Period 2) valsartan will be optionally titrated from 1 mg/kg to 2 mg/kg. Valsartan will continue to be optionally up titrated in 1 mg/kg increments every 4 weeks until maximum dose of 4 mg/kg is achieved. Duration 20 weeks.
Drug: VAL489
Valsartan 3mg/kg oral solution
Other Name: Diovan

  Eligibility

Ages Eligible for Study:   1 Year to 5 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients eligible for inclusion in this study have to fulfill all of the following criteria:

Have the ability to provide written informed consent; Have at baseline , a documented diagnosis of hypertension (as defined in the National High Blood Pressure Education Program 2004); MSBP (mean of 3 measurements) must be ≥95th percentile, and ≤25% above the 95th percentile, for age, gender and height, at baseline; CKD patients must be defined as any of the following criteria: Kidney damage for ≥3 months, as defined by structural or functional abnormalities of the kidney, with or without decreased GFR, manifested by one or more of the following features: Abnormalities in the composition of urine, Abnormalities in imaging tests, Abnormalities on kidney biopsy, Estimated eGFR <60 mL/min/1.73m2 for ≥3 months, with or without the other signs of kidney damage described above; Able to swallow the valsartan solution; Body weight must be ≥8 kg and ≤40 kg at baseline; Must be able to safely washout from other antihypertensive therapy (if applicable) Exclusion criteria AST/SGOT or ALT/SGPT >3 times the upper limit of the reference range; Estimated Glomerular Filtration Rate [eGFR] <30 mL/min/1.73m² (calculated using Modified Schwartz Formula); Serum potassium >5.3 mmol/L; Uncontrolled diabetes mellitus, as defined by the investigator; Unilateral, bilateral and graft renal artery stenosis; Current diagnosis of heart failure (NYHA Class II-IV); Patients taking any of the following concomitant medications following screening: RAAS blockers other than study drug, Lithium, Potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium and other substances that may increase potassium levels; Non-steroidal anti-inflammatory drugs (NSAIDS), including selective COX-2 inhibitors, acetylsalicylic acid >3g/day, and non-selective NSAIDs (paracetamol/acetaminophen is permitted); Antidepressant drugs in the class of MAO inhibitors (e.g. phenelzine); Chronic use of stimulant therapy for ADD/ADHD; patients who have coarctation of the aorta with a gradient of ≥30 mmHg; Previous solid organ transplantation except renal transplantation. Renal transplant must have occurred at least 1 year prior to enrollment; Patient must be on stable doses of immunosuppressive therapy and deemed clinically stable by the investigator; Patients known to be positive for the human immunodeficiency virus (HIV) Other protocol defined inclusion/exclusion criteria may apply.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01617681

Contacts
Contact: Novartis Pharmaceuticals +41613241111
Contact: Novartis Pharmaceuticals

  Show 45 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01617681     History of Changes
Other Study ID Numbers: CVAL489K2306, 2011-005991-40
Study First Received: June 6, 2012
Last Updated: October 6, 2014
Health Authority: United States: Food and Drug Administration
Belgium: Institutional Review Board

Keywords provided by Novartis:
Hypertension; CKD; Pediatric

Additional relevant MeSH terms:
Hypertension
Cardiovascular Diseases
Vascular Diseases
Valsartan
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Antihypertensive Agents
Cardiovascular Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014