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

Phase 3

Completed

Conditions: Hypertension
Chronic Kidney Disease

Interventions: Drug: Valsartan
Drug: amlodipine
Drug: Hydrochlorothiazide

Registration Number: NCT01365481

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 150

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
valsartan	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.
valsartan	Hydrochlorothiazide	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.
valsartan	amlodipine	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.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) at End Point (Week 78 or Last Observation Carried Forward (LOCF)	Baseline, End Point (Week 78 or Last observation carried forward (LOCF)	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)	Baseline, End Point (Week 78 or Last observation carried forward (LOCF)	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

Name	Time	Method
Number of Participants With MSSBP, MSDBP and (MSSBP and MSDBP Combined) < 95th Percentile for Gender, Age, and Height	End Point (Week 78 or Last observation carried forward (LOCF)	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 Estimated Glomerular Filtration Rate (eGFR) Decrease > 25 % From Baselinefrom Baseline to End Point	Baseline, End Point (Week 78 or Last observation carried forward (LOCF)	Percentage of Patients with CKD who had eGFR decrease \> 25 % from Baseline
Percentage of Chronic Kidney Disease (CKD) Patients Who Had >=50% Reduction in Urine Albumin/Creatinine Ratio (UACR) From Baseline to End Point	Baseline, End Point (Week 78 or Last observation carried forward (LOCF)	Percentage of Patients with CKD who had Urine albumin creatinine reduction \>/= 50% from baseline