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

Hypertension Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01365481
• Other study ID #: CVAL489K2305
• Secondary ID: 2009-017594-37
• Status: Completed
• Phase: Phase 3
• First received: May 9, 2011
• Last updated: April 19, 2016
• Start date: August 2011
• Est. completion date: September 2015

Study information

• Verified date: April 2016
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationColombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y AlimentosColombia: Institutional Review BoardGuatemala: Ministry of HealthFinland: Ethics CommitteeFinland: Ministry of Social Affairs and HealthFinland: Finnish Medicines AgencyGermany: Ethics CommissionGermany: Federal Institute for Drugs and Medical DevicesGermany: Federal Ministry of Education and ResearchGermany: Federal Ministry of Food, Agriculture and Consumer ProtectionGermany: German Institute of Medical Documentation and InformationGermany: Ministry of HealthGermany: Paul-Ehrlich-InstitutPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsPoland: Ministry of HealthPoland: Ministry of Science and Higher EducationRomania: Ministry of Public HealthRomania: National Medicines AgencyRomania: State Institute for Drug ControlPhilippines: Department of HealthPhilippines: Bureau of Food and DrugsSingapore: Clinical Trials & Epidemiology Research Unit (CTERU)Singapore: Domain Specific Review BoardsSingapore: Health Sciences AuthorityIndia: Central Drugs Standard Control OrganizationIndia: Department of Atomic EnergyIndia: Drugs Controller General of IndiaIndia: Indian Council of Medical ResearchIndia: Institutional Review BoardIndia: Ministry of HealthIndia: Ministry of Science and TechnologyIndia: Science and Engineering Research CouncilRussia: Ethics CommitteeRussia: FSI Scientific Center of Expertise of Medical ApplicationRussia: Ministry of Health of the Russian FederationRussia: Pharmacological Committee, Ministry of HealthGuatemala: Ministry of Public Health and Social Assistance
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: September 2015
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Years to 17 Years

Eligibility

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

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Kidney Disease
• Hypertension
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

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

Locations

Country	Name	City	State
Colombia	Novartis Investigative Site	Barranquilla
Colombia	Novartis Investigative Site	Bucaramanga	Santander
Colombia	Novartis Investigative Site	Cali
Finland	Novartis Investigative Site	Helsinki
Germany	Novartis Investigative Site	Bochum
Germany	Novartis Investigative Site	Cottbus
Germany	Novartis Investigative Site	Freiburg
Germany	Novartis Investigative Site	Homburg
Germany	Novartis Investigative Site	Rostock
Guatemala	Novartis Investigative Site	Guatemala City
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Philippines	Novartis Investigative Site	Manila
Philippines	Novartis Investigative Site	Quezon City
Philippines	Novartis Investigative Site	Quezon City
Poland	Novartis Investigative Site	Warszawa
Romania	Novartis Investigative Site	Bucuresti
Romania	Novartis Investigative Site	Bucuresti
Romania	Novartis Investigative Site	Cluj-Napoca	Jud Cluj
Romania	Novartis Investigative Site	Iasi
Romania	Novartis Investigative Site	Tg. Mures	jud Mures
Romania	Novartis Investigative Site	Timisoara	jud. Timis
Russian Federation	Novartis Investigative Site	Kazan
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Voronezh
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Colombia,  Finland,  Germany,  Guatemala,  Korea, Republic of,  Philippines,  Poland,  Romania,  Russian Federation,  Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Primary	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)	No
Secondary	Number of Participants With MSSBP, MSDBP and (MSSBP and MSDBP Combined) < 95th Percentile for Gender, Age, and Height	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	End Point (Week 78 or Last observation carried forward (LOCF)	No
Secondary	Percentage of Chronic Kidney Disease (CKD) Patients Who Had >=50% Reduction in Urine Albumin/Creatinine Ratio (UACR) From Baseline to End Point	Percentage of Patients with CKD who had Urine albumin creatinine reduction >/= 50% from baseline	Baseline, End Point (Week 78 or Last observation carried forward (LOCF)	Yes
Secondary	Percentage of Chronic Kidney Disease (CKD) Patients Who Had Estimated Glomerular Filtration Rate (eGFR) Decrease > 25 % From Baselinefrom Baseline to End Point	Percentage of Patients with CKD who had eGFR decrease > 25 % from Baseline	Baseline, End Point (Week 78 or Last observation carried forward (LOCF)	Yes