ACEIs are a cornerstone of treatment for paediatric heart failure (HF) but prior to Aqumeldi®:1
- Insufficient paediatric data for ACEI dose-PK relationships in heart failure existed, so dose estimates were often extrapolated from adult patients1
- No licensed enalapril suitable for use in children with heart failure was available in Europe1
LENA (Labelling Enalapril from Neonates up to Adolescents) Project
The LENA project was a collaboration of European Professors and Paediatric Cardiologists funded by the European Commission with the aim of developing an effective and clinically safe, orally administered age-appropriate formulation of enalapril for paediatric use in Europe.1-3
It comprised of multiple research studies including pharmacokinetics modelling, bioavailability assessments, pharmacokinetic bridging and clinical safety.
Note: The project was initiated independently from industry. Proveca was chosen to manage the licensing and launch of the medication due to their expertise and commitment in developing medicines for children.
Studies Summary
- The first PK data of enalapril and its metabolite enalaprilat after administration of a mini orodispersible formulation to paediatric patients with HF.3
- The rate and extent of enalapril absorption from the novel formulation were shown to be equivalent to that from conventional enalapril tablets.2
- The acceptability and palatability assessment demonstrated that enalapril mini ODT is an appropriate and reliable form of drug administration, even in very young patients.4,5
- No rehospitalisation due to HF, no mechanical circulatory support, no transplantation and no death reported in the studies6
- No drug related serious adverse events4-6
Additional Study Details
PK Bridging Studies - Objectives 4,5
Primary Objective
- To obtain paediatric pharmacokinetic data of enalapril and its active metabolite enalaprilat in patients treated with enalapril mini ODTs to describe the dose exposure in the paediatric population with dilated cardiomyopathy (DCM) or congenital heart disease (CHD)
Seconday Objectives
- To demonstrate safety, in particular renal safety, of enalapril mini ODTs in children with DCM or CHD
- To characterise the dose/safety relationship from a starting dose to an optimal maintenance dose
- To explore the dose exposure/response relationship with pharmacodynamic parameters in the paediatric population with DCM or CHD
- To investigate the Shortening Fraction (SF) in echocardiography
- To investigate the acceptability and palatability of enalapril mini ODTs in the paediatric population with DCM or CHD
PK Bridging Studies - Primary Results 2-5
- The PK results demonstrated that an appropriate enalapril exposure with enalapril mini ODT had been achieved2-5
- AUC and Cmax were successfully characterised in both populations and in all age groups4,5
- Maximum plasma concentrations were as expected in both populations4,5
- Patient's age influenced the extent and rate of enalapril and enalaprilat exposure3
Acceptability Data 4,5
- Patient acceptability is likely to have a significant impact on patient adherence and consequently on the safety and efficacy of the medicine4,5
- The acceptability and palatability assessment demonstrated that enalapril mini ODT is an appropriate and reliable form of drug administration, even in very young patients4,5
- Acceptability was recorded at 100% for both DCM and CHD patients4,5
- Palatability was recorded at 97% for both DCM and CHD patients4,5
Contact Form
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