Hypertension in children under the age of 6 years
Conditions
Interventions
Product Name: Candesartan cilexetil 0,1 mg/ml
Pharmaceutical Form: Oral suspension
INN or Proposed INN: Candesartan cilexetil
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equa
Sponsors
AstraZeneca Pharmaceuticals
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: For study inclusion, subjects must fulfill all eligibility criteria 1) Signed informed consent by a parent or a legal guardian 2) Age 1 to less than 6 years 3) Weight ³ 10 kg and £ 40 kg 4) SiSBP and/or SiDBP ³ 95th percentile and £ 20 mm Hg (systolic) and/or 10 mm Hg (diastolic) above the 95th percentile at screening and at randomization based on height-adjusted charts for age and gender (Appendices C through H) 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
Exclusion criteria: The following exclude subjects from study participation: 1) Any situation, clinical condition or laboratory abnormality that, in the opinion of the investigator or sponsor, may interfere with the subject’s participation in the study or would pose a significant risk to the subject or interfere with the assessment of safety and efficacy endpoints 2) Weight 40 kg 3) Less than 80% compliance with study medication during single-blind placebo screening as assessed by residual medication volume 4) Hypertension secondary to pheochromocytoma, hyperthyroidism, or Cushing’s syndrome 5) Uncorrected coarctation of the aorta, bilateral renal artery stenosis, or unilateral renal artery stenosis in a single kidney 6) Estimated glomerular filtration rate (GFR) 50 mL/min/1.73m2, 3) stable doses of immunosuppressive medications are anticipated throughout the 4-week, double-blind period of the study, 4) no episodes of acute allograft rejection have occurred within 30 days of study entry, and 5) the renal allograft has no documented renal artery stenosis 8) Nephrotic syndrome not in remission 9) Unstable insulin dependent diabetes mellitus 10) Known bleeding, coagulation, or platelet disorder that could interfere with blood sampling 11) Clinically significant valvular heart disease 12) Clinical diagnosis of heart failure 13) Clinically significant arrhythmia (eg, any arrhythmia requiring medical therapy or that causes symptoms) 14) Second or third degree AV block 15) Impaired liver function defined as either acute liver disease or chronic liver disease with persistent liver enzyme values greater than 1½ times the upper limit of the reference range for aspartate aminotransferase (AST) or alanine aminotransferase (ALT) 16) Known hypersensitivity to ARBs 17) Currently receiving an angiotensin receptor blocker or an angiotensin converting enzyme inhibitor that in the investigator’s judgement cannot safely be withdrawn during the study Subjects receiving an angiotensin receptor blocker or an angiotensin converting enzyme inhibitor may be eligible if they undergo withdrawal of the antihypertensive medication over a 2-week washout period and subsequently meet BP inclusion/exclusion criteria. Subjects currently receiving other classes of antihypertensive medications (eg, diuretics, calcium channel blockers or beta-blockers) and whose BP values meet inclusion/exclusion criteria may participate in the study while continuing their current antihypertensive medication regimen. Up to 2 concomitant antihypertensive medications are permitted. Doses and dose regimens of concomitant antihypertensive medications must remain unchanged during the 4-week double-blind period of the study. 18) Currently using, or used within 14 days prior to receiving double-blind medication, any concomitant medications which in the opinion of the investigator could negatively affect the subject 19) Unable or unwilling to comply with the study requirements including blood sampling and swallowing study drug suspension 20) Received an investigational agent within 30 days prior to receiving study medication
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to characterize the dose response relationship of candesartan cilexetil (once-daily) in hypertensive pediatric subjects (1 to <6 years of age) by evaluation of the slope of the linear regression for the change in trough SiSBP from baseline (Day 0) to the end of the 4-week double-blind treatment period (Day 28) as a function of dose. ;Secondary Objective: Dose response relationship of Atacand for the change in trough SiSBP from baseline to the end of the double-blind treatment period as a function of dose for each of the 2 body weight panels Dose response relationship of Atacand for the change in trough SiDBP, SuSBP, and SuDBP from baseline to the end of the double-blind treatment period as a function of dose Mean change in trough SiSBP, SuSBP, SiDBP, and SuDBP for Atacand from baseline to the end of the double-blind treatment period Change in urinary protein/creatinine and urinary albumin/creatinine ratio from baseline to the end of the double-blind treatment period and to the end of the open-label treatment period Safety as assessed by adverse events, adverse events that necessitate study drug discontinuation, serious adverse events, physical exam findings, ECG, and laboratory tests during the double-blind treatment period and the open-label treatment period Pharmacokinetics Medication adherence ;Primary end point(s): The primary efficacy endpoint of this study is the slope of linear regression for the change in trough SiSBP from baseline (Day 0) to the end of the 4-week double-blind treatment period (Day 28) as a function of dose for subjects 1 to less than 6 years of age with hypertension based on the ITT population. Safety endpoints include 1) Incidence of AEs 2) Incidence of discontinuations due to any AE 3) SAEs 4) Heart rate and change in heart rate 5) Clinical laboratory test results 6) Physical examination and ECG findings 7) Height/Length, Weight, and Head circumference (in children of age <2 | — |
Countries
Belgium, Denmark, Germany, Italy, United Kingdom
Outcome results
None listed