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

May 9, 2011
June 13, 2016
August 2011
September 2015   (final data collection date for primary outcome measure)
  • 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.
To assess the long-term safety and tolerability profile of valsartan in children with hypertension, with or without chronic kidney disease. [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
Adverse events will be summarized by primary system organ class and preferred terms, laboratory data will be summarized for change from baseline, for shift with respect to normal range, and for occurrence of abnormality as appropriate.
Complete list of historical versions of study NCT01365481 on ClinicalTrials.gov Archive Site
  • 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
  • To assess the long-term efficacy of valsartan in reducing the mean sitting systolic (MSSBP) and mean sitting diastolic blood pressure (MSDBP) in children with hypertension. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • To assess the long-term efficacy of valsartan in controlling the MSSBP and MSDBP in children with hypertension. The target mean BP is <95th percentile for age, gender and height. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • To assess the effect of valsartan and valsartan-based treatments on proteinuria and eGFR in a subset of children with hypertension and chronic kidney disease. [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Safety and Tolerability of Valsartan in Children 6 to 17 Years of Age
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
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.
Not Provided
Interventional
Phase 3
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Hypertension
  • Chronic Kidney Disease
  • 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
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.
Interventions:
  • Drug: Valsartan
  • Drug: amlodipine
  • Drug: Hydrochlorothiazide
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
150
September 2015
September 2015   (final data collection date for primary outcome measure)

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

Both
6 Years to 17 Years   (Child)
No
Contact information is only displayed when the study is recruiting subjects
Colombia,   Finland,   Germany,   Guatemala,   Korea, Republic of,   Philippines,   Poland,   Romania,   Russian Federation,   Singapore
Argentina,   India
 
NCT01365481
CVAL489K2305, 2009-017594-37
No
Not Provided
Not Provided
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
June 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP