Dose Ranging, Safety and Tolerability of TOPROL-XL® Extended-Release Tablets in Hypertensive Pediatric Subjects
Summary
This was a 4-week, multicenter, double-blind, placebo-controlled, randomized, parallel-group study to determine the antihypertensive dose range, efficacy, safety and tolerability of TOPROL-XL ® (metoprolol succinate) extended-release tablets (metoprolol CR/XL) in hypertensive pediatric subjects. The study population included school age children (age 6 to < Tanner Stage 3) and adolescents (> Tanner Stage 3 to age 16) of both genders. No more than 50% of the randomized subjects could be adolescents (> Tanner Stage 3 to 16 years old). Since response to some therapies in adult hypertension appears to be different in black and non-black populations, recruitment was aimed at a mixture of black and non-black children. The design included a 1-week screening period (for treatment naive subjects), a 1-week single-blind placebo run-in period, and a 4-week double-blind treatment period. Eligible subjects were randomized to the double-blind period with a once daily oral dose of metoprolol CR/XL to one of three target doses: 0.2, 1.0 and 2.0 mg/kg, or placebo. Dosing was weight adjusted. The dose range for this study was 12.5 to 200 mg daily. Subjects were closely monitored and evaluated at the end of Weeks 1, 2, 3 and 4 during the double-blind treatment period.
Study Design
Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment
Conditions
Hypertension
Intervention
metoprolol succinate
Location
Research Site
Little Rock
Arkansas
United States
Status
Completed
Source
AstraZeneca
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00255528
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Succinate-coa Ligases
Enzymes that catalyze the first step leading to the oxidation of succinic acid by the reversible formation of succinyl-CoA from succinate and CoA with the concomitant cleavage of ATP to ADP (EC 6.2.1.5) or GTP to GDP (EC 6.2.1.4) and orthophosphate. Itaconate can act instead of succinate and ITP instead of GTP.EC 6.2.1.-.
Metoprolol
A selective adrenergic beta-1-blocking agent with no stimulatory action. It's binding to plasma albumin is weaker than alprenolol and it may be useful in angina pectoris, hypertension, or cardiac arrhythmias.
Succinate-semialdehyde Dehydrogenase
An enzyme that plays a role in the GLUTAMATE and butanoate metabolism pathways by catalyzing the oxidation of succinate semialdehyde to SUCCINATE using NAD+ as a coenzyme. Deficiency of this enzyme, causes 4-hydroxybutyricaciduria, a rare inborn error in the metabolism of the neurotransmitter 4-aminobutyric acid (GABA).
Succinate Dehydrogenase
A flavoprotein containing oxidoreductase that catalyzes the dehdyrogenation of SUCCINATE to fumerate. In most eukaryotic organisms this enzyme is a component of mitochondrial electron transport complex II.
Succinate-semialdehyde Dehydrogenase (nadp+)
An enzyme that catalyzes the oxidation of succinate semialdehyde to SUCCINIC ACID. It plays a role in the metabolism of GLUTAMATE; TYROSINE; and butanoate.
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