ORODISPERSIBLE MINITABLETS OF ENALAPRIL IN YOUNG CHILDREN WITH HEART FAILURE DUE TO CONGENITAL HEART DISEASE

• Register: EUCTR
• Last refreshed on: 11 April 2016
• Main ID: EUCTR2015-002396-18-NL
• Date of registration: 12/10/2015
• Prospective Registration: Yes
• Primary sponsor: Ethicare GmbH
• Public title: ORODISPERSIBLE MINITABLETS OF ENALAPRIL IN YOUNG CHILDREN WITH HEART FAILURE DUE TO CONGENITAL HEART DISEASE
• Scientific title: ORODISPERSIBLE MINITABLETS OF ENALAPRIL IN YOUNG CHILDREN WITH HEART FAILURE DUE TO CONGENITAL HEART DISEASE - ENACHD
• Date of first enrolment: 04/12/2015
• Target sample size: 50
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-002396-18
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: yes Other trial design description: Group 1: ACEI-pretreated patients. Group B: ACEI-naive patients If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Austria, Hungary, Netherlands, Serbia, United Kingdom

Contacts

• Name: Lead Clinical Project Manager
• Affiliation: Pharmaplex bvba

• Name: Lead Clinical Project Manager
• Affiliation: Pharmaplex bvba

Key inclusion & exclusion criteria

Inclusion criteria:
• Age from birth to less than 6 years.
• Male and female patients.
• Weight greater than 2.5 Kg.
• Diagnosis of heart failure due to congenital heart disease requiring after load reduction by drug therapy.
• Subjects may be naïve to ACE-Inhibitors (ACEI).
• Subjects already on ACE-Inhibitors willing to switch to Enalapril Orodispersable Minitablets.
• Patient and/or parent(s)/legal representative provided written informed consent.

Permitted:
Other CHF medications are allowed, at the discretion of the investigator. These include but are not limited to diuretics, beta-blockers, digoxin, mineralocorticoid receptor antagonist, aspirin and paracetamol.

Are the trial subjects under 18? yes
Number of subjects for this age range: 50
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:
• Neonates if born < 37 weeks gestation.
• Severe HF and/or end stage heart failure requiring ICU support precluding introduction or continuation of ACEI.
• Too low blood pressure, e.g. belowP5
• Uncorrected primary obstructive valvular disease, or significant systemic ventricular outflow obstruction, dilated restrictive or hypertrophic cardiomyopathy.
• Uncorrected severe peripheral stenosis of large arteries including severe coarctation of the aorta.
• Severe renal impairment with serum creatinine >2x ULN (Upper Limit of Normal) according to the hospital’s test methodology).
• History of Angioedema.
• Hypersensitivity to ACEI.
• Concomittant medication:
o Dual ACEI therapy
o Renin inhibitors
o Angiotensin II antagonists
o NSAIDs except for aspirin acetylsalicylic acid only for antiplatelet therapy
• Already enrolled in an interventional trial with an investigational drug, unless no interference with the current study can be shown.



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

Health Condition(s) or Problem(s) studied

Heart Failure due to Congenital Heart Disease
MedDRA version: 18.1 Level: LLT Classification code 10010495 Term: Congenital heart disease NOS System Organ Class: 100000004850

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Intervention(s)

Product Name: Enalapril Orodispersible Minitablets (ODMT)
Pharmaceutical Form: Orodispersible tablet
INN or Proposed INN: Enalapril Maleate
CAS Number: 76095-16-4
Current Sponsor code: ENA10BA
Other descriptive name: ENALAPRIL MALEATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-

Product Name: Enalapril Orodispersible Minitablet (ODMT)
Pharmaceutical Form: Orodispersible tablet
INN or Proposed INN: Enalapril maleate
CAS Number: 76095-16-4
Current Sponsor code: ENA10BA
Other descriptive name: ENALAPRIL MALEATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.25-

Primary Outcome(s)

Main Objective: To obtain paediatric pharmacokinetic data of enalapril and its active metabolite enalaprilat in patients treated with enalapril ODMTs to describe the dose exposure in the paediatric population with CHD.

Secondary Objective: • To demonstrate safety, in particular renal safety, of enalapril ODMTs in children with 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 CHD.
• To investigate the Shortening Fraction (SF) of the heart muscle by echocardiography.
• To investigate the acceptability and palatability of enalapril ODMTs in the paediatric population with CHD.

Timepoint(s) of evaluation of this end point: PK/PD profile sampling timepoints: Visit day 1: pre-dose, 0h, 2, 4, 6, 8, 12 hours

Primary end point(s): The bioavailability of enalapril and its active metabolite enalaprilat in young children (AUC from 0 to time of last sampling point, Cmax and Tmax); descriptive pharmacokinetic investigation.

Secondary Outcome(s)

Secondary end point(s): The bioavailability of enalapril and its active metabolite enalaprilat in the different age subsets (0 to ?12 months and 12 months to ?6 years) of the paediatric study population (AUC from 0 to time of last sampling point, Cmax and Tmax); descriptive pharmacokinetic investigation.
Markers of the renin-angiotensin-aldosterone system as exploratory pharmaco-dynamic investigation.
Brain natriuretic peptides (BNPs).
Acceptability and palatability of the novel formulation.
Safety parameters including blood pressure and renal function.
Echocardiography (Shortening Fraction)
Rehospitalisation due to heart failure including the need for heart transplantation or the institution of mechanical circulatory support.
Death due to worsening of the underlying disease.
Pharmacodynamic and efficacy endpoints analysis to differentiate high and low output disease.

Timepoint(s) of evaluation of this end point: Biochemistry, Urine and BNP collected during each visit in the hospital to monitor renal function.
PK and PD 1 sample collected during each visit, unless the patient
terminated use of the IMP, then only PD sample is collected.
Acceptability and Palatability questionnaire is completed during initial
visit, once stable dose is reached and during end of study visit.

Secondary ID(s)

2015-002396-18-HU

602295

2015-602295-02

Source(s) of Monetary Support

European Commission FP7 grant agreement 602295