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

• ClinicalTrials.gov Identifier: NCT01365481
• Recruitment Status: Completed
• First Posted: June 3, 2011
• Results First Posted: April 21, 2016
• Last Update Posted: July 13, 2016
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Hypertension; Chronic Kidney Disease	Drug: Valsartan; Drug: amlodipine; Drug: Hydrochlorothiazide	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 150 participants
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: August 2011
• Actual Primary Completion Date: September 2015
• Actual Study Completion Date: September 2015

Arms and Interventions

Arm

Intervention/treatment

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

Outcome Measures

Primary Outcome Measures :

1. 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) ]
   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.
2. 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) ]
   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 :

1. 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) ]
   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
2. 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) ]
   Percentage of Patients with CKD who had Urine albumin creatinine reduction >/= 50% from baseline
3. 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) ]
   Percentage of Patients with CKD who had eGFR decrease > 25 % from Baseline

Eligibility Criteria

• Ages Eligible for Study: 6 Years to 17 Years (Child)
• Sexes Eligible for Study: All
• 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

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, 041451

Novartis Investigative Site

Bucuresti, Romania, 20395

Novartis Investigative Site

Iasi, Romania, 700309

Russian Federation

Novartis Investigative Site

Kazan, Russian Federation, 420012

Novartis Investigative Site

Moscow, Russian Federation, 119991

Novartis Investigative Site

Moscow, Russian Federation, 125315

Novartis Investigative Site

Moscow, Russian Federation, 127412

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 ( EudraCT Number )
• First Posted: June 3, 2011
• Results First Posted: April 21, 2016
• Last Update Posted: July 13, 2016
• Last Verified: June 2016

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

Hypertension, pediatric; Hypertension with or without chronic kidney disease

Additional relevant MeSH terms:

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