Safety and Tolerability of Valsartan in Children 6 to 17 Years of Age

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01365481
First received: May 9, 2011
Last updated: June 13, 2016
Last verified: June 2016
  Purpose
The purpose of this study is to assess the long-term safety and tolerability profile of valsartan and valsartan-based treatments in children with hypertension, with or without chronic kidney disease.

Condition Intervention Phase
Hypertension
Chronic Kidney Disease
Drug: Valsartan
Drug: amlodipine
Drug: Hydrochlorothiazide
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter, Open-label, 18 Month Study to Evaluate the Long-term Safety and Tolerability of Valsartan in Children 6 to 17 Years of Age With Hypertension and With or Without Chronic Kidney Disease

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) at End Point (Week 78 or Last Observation Carried Forward (LOCF) [ Time Frame: Baseline, End Point (Week 78 or Last observation carried forward (LOCF) ] [ Designated as safety issue: No ]
    Sitting blood pressure was measured using a calibrated standard sphygmomanometer after the participants remained in sitting position for 5 minutes at clinic during the visit. The repeat sitting measurements were made at 2 to 3 minute intervals and the mean of three sSBP measurements were used as the average sitting office blood pressure for that visit.

  • Change From Baseline in Mean Sitting Diastolic Blood Pressure (MsDBP) at End Point (Week 78 or Last Observation Carried Forward (LOCF) [ Time Frame: Baseline, End Point (Week 78 or Last observation carried forward (LOCF) ] [ Designated as safety issue: No ]
    Sitting blood pressure was measured using a calibrated standard sphygmomanometer after the participants remained in sitting position for 5 minutes at clinic during the visit. The repeat sitting measurements were made at 2 to 3 minute intervals and the mean of three sDBP measurements were used as the average sitting office blood pressure for that visit.


Secondary Outcome Measures:
  • Number of Participants With MSSBP, MSDBP and (MSSBP and MSDBP Combined) < 95th Percentile for Gender, Age, and Height [ Time Frame: End Point (Week 78 or Last observation carried forward (LOCF) ] [ Designated as safety issue: No ]
    Number of Participants with Mean sitting systolic (MSSBP) and mean sitting diastolic(MSDBP) blood pressure and both combined less than the 95th percentile for age, gender and height

  • Percentage of Chronic Kidney Disease (CKD) Patients Who Had >=50% Reduction in Urine Albumin/Creatinine Ratio (UACR) From Baseline to End Point [ Time Frame: Baseline, End Point (Week 78 or Last observation carried forward (LOCF) ] [ Designated as safety issue: Yes ]
    Percentage of Patients with CKD who had Urine albumin creatinine reduction >/= 50% from baseline

  • Percentage of Chronic Kidney Disease (CKD) Patients Who Had Estimated Glomerular Filtration Rate (eGFR) Decrease > 25 % From Baselinefrom Baseline to End Point [ Time Frame: Baseline, End Point (Week 78 or Last observation carried forward (LOCF) ] [ Designated as safety issue: Yes ]
    Percentage of Patients with CKD who had eGFR decrease > 25 % from Baseline


Enrollment: 150
Study Start Date: August 2011
Study Completion Date: September 2015
Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: valsartan
Valsartan starting dose: ≥18 kg to <35 kg is 40 mg, ≥35 kg to <80 kg is 80 mg, ≥80 kg to ≤160 kg is 160 mg for 1 week then Valsartan maintenance dose: ≥18 kg to <35 kg is 80 mg, ≥35 kg to <80 kg is 160 mg, ≥80 kg to ≤160 kg is 320 mg after Week 8 if the Mean Sitting Systolic Blood Pressure (MSSBP) and/or Mean Sitting Diastolic Blood Pressure (MSDBP) was higher than 95th percentile for age, gender and height under the maintenance valsartan dose then add amlodipine and/or Hydrochlorothiazide (HCTZ). The valsartan +antihypertensive group includes patients who received background antihypertensive medication or received antihypertensive medication including amlodipine or HCTZ during the study.
Drug: Valsartan
week 1: 40/80/160 week 2-78: 80/160/320mg, oral, by mouth, once daily
Other Name: VAL489
Drug: amlodipine
added to valsartan after week 8 if the MSSBP and/or MSDBP was higher than 95th percentile for age, gender and height under the maintenance valsartan dose
Drug: Hydrochlorothiazide
added to valsartan after week 8 if the MSSBP and/or MSDBP was higher than 95th percentile for age, gender and height under the maintenance valsartan dose
Other Name: HCTZ

  Eligibility

Ages Eligible for Study:   6 Years to 17 Years   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Documented diagnosis of hypertension
  • able to swallow a tablet
  • body weight ≥18 kg and ≤160 kg at baseline
  • MSSBP must be ≥ 95th percentile and ≤25% above the 95th percentile for age, gender and height.

Exclusion Criteria:

  • Any clinically significant physical abnormalities or clinically relevant abnormal laboratory values (other than those relating to renal function) obtained at the screening visit. Including the following:

    1. AST/SGOT or ALT/SGPT >3 times the upper limit of the reference range. Patients known to have active or chronic hepatitis were excluded.
    2. Total bilirubin >2 times the upper limit of the reference range
    3. Estimated GFR <30 mL/min/1.73m² (calculated using Modified Schwartz Formula)
    4. WBC count <3000/mm³
    5. Platelet count <100,000/mm³
    6. Serum potassium >5.3 mmol/L
    7. Hemoglobin <8 g/dL
  • Uncontrolled diabetes mellitus
  • Unilateral, bilateral and graft renal artery stenosis
  • Current diagnosis of heart failure (New York Heart Association Class II-IV)
  • Patients taking any of the following concomitant medications following screening: Renin-angiotensin receptor(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, Antidepressant drugs in the class of Monoamine oxidase (MAO) inhibitors (e.g. phenelzine), Chronic use of stimulant therapy for Attention deficit disorder/attention deficit hyperactivity disorder (ADD/ADHD) -Patients who demonstrate clinically significant ECG abnormalities such as concurrent potentially life threatening arrhythmia or symptomatic arrhythmia and patients with second or third degree heart block without a pacemaker.
  • Coarctation of the aorta with a gradient of >=30 mmHg
  • Previous solid organ transplantation except renal transplantation.
  • Patients known to be positive for the human immunodeficiency virus (HIV)
  • Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of the study drug
  • Known or suspected contraindications to the study drug, including severe hepatic impairment, biliary cirrhosis, cholestasis and history of allergy to ARBs and/or angiotensin-converting enzymes (ACE) and/or Direct Renin Inhibitors (DRIs)
  • History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin.
  • History or evidence of drug or alcohol abuse within the last 12 months.
  • Female patients of child-bearing potential, defined as all female patients physiologically capable of becoming pregnant, unless they are willing to use highly effective contraception during the study
  • Pregnant or nursing (lactating) female patients
  • Participation in any investigational drug study within 30 days prior to screening or within 5 elimination half-lives of the study drug prior to screening, or whichever is longer.
  • History of hypersensitivity to the study drug or to drugs of similar chemical classes.

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: NCT01365481

Locations
Colombia
Novartis Investigative Site
Bucaramanga, Santander, Colombia, 0001
Novartis Investigative Site
Barranquilla, Colombia
Novartis Investigative Site
Cali, Colombia
Finland
Novartis Investigative Site
Helsinki, Finland, 00029
Germany
Novartis Investigative Site
Bochum, Germany, 44791
Novartis Investigative Site
Cottbus, Germany, 03048
Novartis Investigative Site
Freiburg, Germany, 79106
Novartis Investigative Site
Homburg, Germany, 66421
Novartis Investigative Site
Rostock, Germany, 18107
Guatemala
Novartis Investigative Site
Guatemala City, Guatemala, 01010
Korea, Republic of
Novartis Investigative Site
Seoul, Korea, Korea, Republic of, 03080
Philippines
Novartis Investigative Site
Manila, Philippines, 1000
Novartis Investigative Site
Quezon City, Philippines, 1100
Novartis Investigative Site
Quezon City, Philippines, 1101
Poland
Novartis Investigative Site
Warszawa, Poland, 04-154
Romania
Novartis Investigative Site
Cluj-Napoca, Jud Cluj, Romania
Novartis Investigative Site
Tg. Mures, jud Mures, Romania, 540104
Novartis Investigative Site
Timisoara, jud. Timis, Romania, 300011
Novartis Investigative Site
Bucuresti, Romania, 20395
Novartis Investigative Site
Bucuresti, Romania, 041451
Novartis Investigative Site
Iasi, Romania, 700309
Russian Federation
Novartis Investigative Site
Kazan, Russian Federation, 420012
Novartis Investigative Site
Moscow, Russian Federation, 127412
Novartis Investigative Site
Moscow, Russian Federation, 125315
Novartis Investigative Site
Moscow, Russian Federation, 119991
Novartis Investigative Site
Voronezh, Russian Federation, 394036
Singapore
Novartis Investigative Site
Singapore, Singapore, 119074
Novartis Investigative Site
Singapore, Singapore, 229899
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01365481     History of Changes
Other Study ID Numbers: CVAL489K2305  2009-017594-37 
Study First Received: May 9, 2011
Results First Received: March 9, 2016
Last Updated: June 13, 2016
Health Authority: United States: Food and Drug Administration
Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos
Colombia: Institutional Review Board
Guatemala: Ministry of Health
Finland: Ethics Committee
Finland: Ministry of Social Affairs and Health
Finland: Finnish Medicines Agency
Germany: Ethics Commission
Germany: Federal Institute for Drugs and Medical Devices
Germany: Federal Ministry of Education and Research
Germany: Federal Ministry of Food, Agriculture and Consumer Protection
Germany: German Institute of Medical Documentation and Information
Germany: Ministry of Health
Germany: Paul-Ehrlich-Institut
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Poland: Ministry of Health
Poland: Ministry of Science and Higher Education
Romania: Ministry of Public Health
Romania: National Medicines Agency
Romania: State Institute for Drug Control
Philippines: Department of Health
Philippines: Bureau of Food and Drugs
Singapore: Clinical Trials & Epidemiology Research Unit (CTERU)
Singapore: Domain Specific Review Boards
Singapore: Health Sciences Authority
India: Central Drugs Standard Control Organization
India: Department of Atomic Energy
India: Drugs Controller General of India
India: Indian Council of Medical Research
India: Institutional Review Board
India: Ministry of Health
India: Ministry of Science and Technology
India: Science and Engineering Research Council
Russia: Ethics Committee
Russia: FSI Scientific Center of Expertise of Medical Application
Russia: Ministry of Health of the Russian Federation
Russia: Pharmacological Committee, Ministry of Health
Guatemala: Ministry of Public Health and Social Assistance

Keywords provided by Novartis:
Hypertension, pediatric
Hypertension with or without chronic kidney disease

Additional relevant MeSH terms:
Hypertension
Kidney Diseases
Renal Insufficiency, Chronic
Vascular Diseases
Cardiovascular Diseases
Urologic Diseases
Renal Insufficiency
Amlodipine
Hydrochlorothiazide
Valsartan
Antihypertensive Agents
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Sodium Chloride Symporter Inhibitors
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists

ClinicalTrials.gov processed this record on July 28, 2016