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

NCT01365481 | Completed Phase 3 Results

• 2 other identifiers: CVAL489K23052009-017594-37
• Study Type: interventional
• Target: 150
• Locations: 10 countries
• Sites: 28

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.

Conditions

Hypertension; Chronic Kidney Disease

Keywords

Hypertension, pediatric; Hypertension with or without chronic kidney disease

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) at 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.

  Baseline, End Point (Week 78 or Last observation carried forward (LOCF)

• Change From Baseline in Mean Sitting Diastolic Blood Pressure (MsDBP) at 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.

  Baseline, End Point (Week 78 or Last observation carried forward (LOCF)

Secondary Outcomes (3)

• 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)

• 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 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)

Study Arms (1)

valsartan

EXPERIMENTAL

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; Drug: amlodipine; Drug: Hydrochlorothiazide

Interventions

Valsartan DRUG

week 1: 40/80/160 week 2-78: 80/160/320mg, oral, by mouth, once daily

Also known as: VAL489

valsartan

amlodipine DRUG

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

valsartan

Hydrochlorothiazide DRUG

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

Also known as: HCTZ

valsartan

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• AST/SGOT or ALT/SGPT \>3 times the upper limit of the reference range. Patients known to have active or chronic hepatitis were excluded.
• Total bilirubin \>2 times the upper limit of the reference range
• Estimated GFR \<30 mL/min/1.73m² (calculated using Modified Schwartz Formula)
• WBC count \<3000/mm³
• Platelet count \<100,000/mm³
• Serum potassium \>5.3 mmol/L
• 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)

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (28)

Novartis Investigative Site

Bucaramanga, Santander Department, 0001, Colombia

Location

Novartis Investigative Site

Barranquilla, Colombia

Location

Novartis Investigative Site

Cali, Colombia

Location

Novartis Investigative Site

Helsinki, Finland, 00029, Finland

Location

Novartis Investigative Site

Bochum, 44791, Germany

Location

Novartis Investigative Site

Cottbus, 03048, Germany

Location

Novartis Investigative Site

Freiburg im Breisgau, 79106, Germany

Location

Novartis Investigative Site

Homburg, 66421, Germany

Location

Novartis Investigative Site

Rostock, 18107, Germany

Location

Novartis Investigative Site

Guatemala City, Departamento de Guatemala, 01010, Guatemala

Location

Novartis Investigative Site

Manila, Philippines, 1000, Philippines

Location

Novartis Investigative Site

Quezon City, Philippines, 1100, Philippines

Location

Novartis Investigative Site

Quezon City, Philippines, 1101, Philippines

Location

Novartis Investigative Site

Warsaw, 04-154, Poland

Location

Novartis Investigative Site

Cluj-Napoca, Jud Cluj, Romania

Location

Novartis Investigative Site

Tg. Mures, Jud Mures, 540104, Romania

Location

Novartis Investigative Site

Timișoara, Jud. Timis, 300011, Romania

Location

Novartis Investigative Site

Bucharest, 041451, Romania

Location

Novartis Investigative Site

Bucharest, 20395, Romania

Location

Novartis Investigative Site

Iași, 700309, Romania

Location

Novartis Investigative Site

Kazan', 420012, Russia

Location

Novartis Investigative Site

Moscow, 119991, Russia

Location

Novartis Investigative Site

Moscow, 125315, Russia

Location

Novartis Investigative Site

Moscow, 127412, Russia

Location

Novartis Investigative Site

Voronezh, 394036, Russia

Location

Novartis Investigative Site

Singapore, Singapore, 119074, Singapore

Location

Novartis Investigative Site

Singapore, Singapore, 229899, Singapore

Location

Novartis Investigative Site

Seoul, Korea, 03080, South Korea

Location

MeSH Terms

Conditions

Hypertension; Renal Insufficiency, Chronic

Interventions

Valsartan; Amlodipine; Hydrochlorothiazide

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Valine; Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential; Dihydropyridines; Pyridines; Chlorothiazide; Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Thiazides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862 -778 -8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2011
• First Posted: June 3, 2011
• Study Start: August 1, 2011
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2015
• Last Updated: July 13, 2016
• Results First Posted: April 21, 2016

Record last verified: 2016-06

Locations

KR (1); FI (1); SG (2); CO (3); DE (5); PH (3); RU (5); GU (1); RO (6); PL (1)