A randomized, multicenter, double-blind, 6 week study to evaluate the dose response of valsartan on blood pressure reduction in children 1-5 years old with hypertension, followed by a 2 week placebo withdrawal period. - ND

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2006-005261-19-IT
• Date of registration: 29/08/2007
• Prospective Registration: No
• Primary sponsor: NOVARTIS FARMA
• Public title: A randomized, multicenter, double-blind, 6 week study to evaluate the dose response of valsartan on blood pressure reduction in children 1-5 years old with hypertension, followed by a 2 week placebo withdrawal period. - ND
• Scientific title: A randomized, multicenter, double-blind, 6 week study to evaluate the dose response of valsartan on blood pressure reduction in children 1-5 years old with hypertension, followed by a 2 week placebo withdrawal period. - ND
• Date of first enrolment: 09/08/2007
• Target sample size: 75
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-005261-19
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: Placebo: Other:

Countries of recruitment

Belgium, France, Germany, Hungary, Italy, Sweden

Key inclusion & exclusion criteria

Inclusion criteria:
The investigator must ensure that all patients who meet all the inclusion criteria and none of the exclusion criteria are offered enrollment in the study. No additional exclusions can be applied by the investigator, in order that the study population will be representative of all eligible patients. 1. Patients who are eligible and able to participate in the study and whose parent(s)/guardian(s) consent in writing (written informed consent) to their doing so after the purpose and nature of the investigation has been clearly explained. 2. Male or female between the ages of 1 to 5 years, at visit 1 with a documented history of hypertension. 3. Must be able to swallow the liquid formulation of the study medication 4. Must be >=8 kg or <= 40 kg 5. Patients, either naïve or treated, must have a documented history of a mean seated systolic blood pressure (mean of three measurements), equal to or greater than 95th percentile for age, gender and height (Appendix 3). 6. Patients with uncontrolled blood pressure, receiving background antihypertensive therapy, may continue on this therapy provided there is no change in dosing regimen. 7. Patient that has had a previous solid organ transplantation more than 1 year ago. Patient must be on stable doses of immunosuppressive therapy and deemed clinically stable by the clinician. Stable doses of immunosuppressive therapy are defined as no change in frequency or total daily doses of immunosuppressive therapy for at least 3 months prior to screening. Doses of immunosuppressive therapy must be maintained throughout Periods 1 and 2 of the study. 8. Parent(s)/guardian(s) are able to follow verbal and/or written instructions in the local language
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Patients whose mean seated systolic blood pressure (mean of three measurements), at the baseline visit (Visit # 2) is >= 25% higher than the 95th percentile for age, gender and height see Appendix 3. 2. Physical examination of patient demonstrates abnormalities that would make this study medically hazardous to the patient. 3. Patients with background ARB therapy. 4. Patients that demonstrate any clinically significant abnormalities or clinically noteworthy abnormal laboratory values (other than those relating to renal function), including but not limited to the following: a. AST/SGOT or ALT/SGPT > 3 times the upper limit of the reference range b. Total bilirubin > 2 times the upper limit of the reference range c. Creatinine clearance < 30 mL/min/1.73m² (calculated using Modified Schwartz formula to estimate glomerular filtration rate [GFR], see section 7.5.5 for formula, based on the serum creatinine concentration obtained at Visit 1 (Screening). d. WBC count < 3000/mm³ e. Platelet count < 100,000/mm³ f. Serum potassium > upper limit of the reference range 5. Patients that demonstrate clinically significant ECG abnormalities other than those associated with left ventricular hypertrophy and AV block controlled with a pacemaker. Examples of clinically significant ECG abnormalities considered exclusionary are as follows: a. Heart Rate out of Range i. Rate < 60 BPM ii. Rate > 165 BPM b. Arrhythmia c. Supraventricular Tachycardia d. Ventricular Tachycardia e. Atrial Tachycardia (Fibrillation, Flutter, etc.) f. Conduction Abnormality g. Complete Atrioventricular Block (without Pacemaker) h. Second Degree AV Block, Type II (without Pacemaker) i. Sinus Node Dysfunction (Pause > 3 seconds or Bradycardia <45BPM) j. Sick Sinus Syndrome k. Repolarization Abnormality l. Prolonged rate-corrected QT (QTc) interval > 460 ms m. Acute Ischemia or Infarction 6. Patients that have coarctation of the aorta with a gradient of >= 30 mm Hg, or renal artery stenosis 7. Patient that has any clinically significant unstable medical condition or chronic disease that would put the patient at risk of experiencing an adverse event associated with the expected pharmacodynamic effects of the study medication. 8. Patient that has experienced a significant clinical illness within 10 days prior to baseline visit. 9. Patient that is known to have tested positive for the hepatitis B surface antigen or hepatitis C antibody. 10. Patient that is known to have tested seropositive for the human immunodeficiency virus (HIV) or patient is concomitantly receiving anti-retroviral therapy. 11. Patient that has a clinically significant abnormality of the hepatic system, or a history of malabsorption or previous gastrointestinal surgery that could affect drug absorption or metabolism. 12. Patient that has a known sensitivity to valsartan or other angiotensin II receptor blockers (ARB). 13. Patient receiving any of the prohibited medications listed in protocol section 6.6.5 unless these medications may be withdrawn ethically, prior to visit 1. 14. Patient has taken an investigational drug within 30 days prior to study drug administration


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

hypertension
MedDRA version: 9.1 Level: LLT Classification code 10020772 Term: Hypertension

Intervention(s)

Product Name: valsartan
Product Code: VAL489K
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Valsartan
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 160-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): The primary efficacy variable is: - Change from baseline in MSSBP (mean sitting systolic blood pressure) The primary analysis is for change from baseline at the Period I endpoint in a dose dependent manner. Baseline is defined as the Week 0 value. The Period I endpoint is defined as the Week 6 value or the last post-baseline observation during Period I carried forward (LOCF).

Secondary Objective: Secondary objective(s): To evaluate the overall safety and tolerability of valsartan in 1 to 5 year old hypertensive children when treated for up to 6 weeks. To evaluate blood pressure change at the end of Period 2 from end of Period 1, when comparing pooled valsartan patients versus pooled placebo patients

Main Objective: Primary objective: To evaluate a dose dependent reduction in MSSBP when comparing three doses of valsartan (0.25 mg,/kg, 1 mg/kg and 4 mg/kg ) over a 6 week period in children 1-5 years old with hypertension ( >= 95th percentile for age, gender, and height).

Secondary ID(s)

CVAL489K2303

2006-005261-19-BE