Clinical trial NCT00244621: Atacand Dose Ranging in Hypertensive Pediatric Subjects 1 Year to Less Than 6 Years of Age
Official title: A Dose-ranging Safety and Pharmacokinetics Study of Candesartan Cilexetil in Hypertensive Pediatric Subjects 1 to Less That 6 Years of Age: A 4-week, Multicenter, Randomized, Double-blind Study With a 1-year, Open-label, Follow-up Period.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypertension
Keywords: Pediatric hypertension
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2005-10-27
Enrollment: 95
Sex: ALL
Minimum age (years): 1
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a dose ranging study of candesartan cilexetil in hypertensive pediatric subjects ages 1 to less than 6 years of age. It employs a double blind, randomized, dose ranging design intended for conduct as a multicenter trial. There are 3 study 'periods': a 1-week placebo run-in, a 4-week double blind treatment, and a 52-week open-label, long-term treatment period. Subjects undergo a screening evaluation, then a 1-week single-blind, placebo run-in, after which eligible subjects are allocated to receive 1 of 3 dose levels of candesartan cilexetil (0.05 mg/kg, or 0.20 mg /kg or 0.40 mg /kg), liquid formulation, in a 1:1:1 ratio for 4-weeks. At the end of randomized dose allocation (Day 28), blood pressure assessment will be performed and subjects may begin the 52-week, open-label treatment period of the study.


Eligibility criteria: Inclusion Criteria:

* Signed informed consent by a parent or a legal guardian.
* Weight \> 10 kg and \< 40 kg.
* SiSBP and/or SiDBP \> 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.

Exclusion Criteria:

* 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.
* Weight \< 10 kg and \> 40 kg.
* Less than 80% compliance with study medication during single-blind placebo screening as assessed by residual medication volume.
* Hypertension secondary to pheochromocytoma, hyperthyroidism, or Cushing's Syndrome.
* Uncorrected coarctation of the aorta, bilateral renal artery renal artery stenosis in a single kidney.
* Estimated glomerular filtration rate (GFR) \< 50 mL/min/1.73m 2 based on the Schwartz Formula (Schwartz et al, 1987).
* Renal transplant \< 6 months prior to study entry. Subjects who have received a renal transplant \> 6 months prior to study entry may participate in the study if: 1) renal function is stable, 2) estimated GFR \>50 mL/min/1.73m 2, 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.

Nephrotic syndrome not in remission.

* Unstable insulin dependent diabetes mellitus.
* Known bleeding, coagulation, or platelet disorder that could interfere with blood sampling.
* Clinically significant valvular heart disease.
* Clinical diagnosis of heart failure.
* Clinically significant arrhythmia (eg, any arrhythmia requiring medical therapy or that causes symptoms).
* Second or third degree AV block.
* 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).
* Known hypersensitivity to ARBs.
* Currently receiving an angiotensin receptor blocker or an angiotensin converting enzyme inhibitor that in the investigator's judgment 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.
* 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.
* Unable or unwilling to comply with the study requirements including blood sampling and swallowing study drug suspension.

Primary outcomes:
measure: Mean Change From Baseline to Week 4 in Systolic Blood Pressure (SBP)
timeFrame: From randomisation to end of double-blind treatment (4 weeks)
Secondary outcomes:
measure: Mean Change From Baseline to Week 4 in Diastolic Blood Pressure (DBP)
timeFrame: From randomisation to end of double-blind treatment (4 weeks)
measure: Change in Albumin/Creatinine (A/C) Ratio for Each Assigned Dose Level From Baseline to Day 28
timeFrame: From randomisation to day 28
measure: Change in Protein/Creatinine (P/C) Ratio for Each Assigned Dose Level From Baseline to Day 28
timeFrame: From randomisation to day 28
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Little Rock
country: United States
facility: Research Site
state: Arkansas
city: Los Angeles
country: United States
facility: Research Site
state: California
city: San Francisco
country: United States
facility: Research Site
state: California
city: Miami
country: United States
facility: Research Site
state: Florida
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Boise
country: United States
facility: Research Site
state: Idaho
city: Detroit
country: United States
facility: Research Site
state: Michigan
city: Durham
country: United States
facility: Research Site
state: North Carolina
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Portland
country: United States
facility: Research Site
state: Oregon
city: Malvern
country: United States
facility: Research Site
state: Pennsylvania
city: Chattanooga
country: United States
facility: Research Site
state: Tennessee
city: Beaumont
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Edegem
country: Belgium
facility: Research Site
city: Gent
country: Belgium
facility: Research Site
city: Arhus
country: Denmark
facility: Research Site
city: Strasbourg Cedex
country: France
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Erlangen
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Heidelberg
country: Germany
facility: Research Site
city: Marburg
country: Germany
facility: Research Site
city: Rostock
country: Germany
facility: Research Site
city: Genova
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Padova
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Gdansk
country: Poland
facility: Research Site
city: Kraków
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: San Juan
country: Puerto Rico
facility: Research Site
city: Crimea
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: AstraZeneca Atacand Medical Science Director, MD
role: STUDY_DIRECTOR
References:
citation: Schaefer F, van de Walle J, Zurowska A, Gimpel C, van Hoeck K, Drozdz D, Montini G, Bagdasorova IV, Sorof J, Sugg J, Teng R, Hainer JW; Candesartan in Children with Hypertension Investigators. Efficacy, safety and pharmacokinetics of candesartan cilexetil in hypertensive children from 1 to less than 6 years of age. J Hypertens. 2010 May;28(5):1083-90. doi: 10.1097/HJH.0b013e328336b86b.