ORODISPERSIBLE MINITABLETS OF ENALAPRIL IN CHILDREN WITH HEART FAILURE DUE TO DILATED CARDIOMYOPATHY

• Register: EUCTR
• Last refreshed on: 24 September 2018
• Main ID: EUCTR2015-002335-17-HU
• Date of registration: 29/09/2015
• Prospective Registration: Yes
• Primary sponsor: Ethicare GmbH
• Public title: ORODISPERSIBLE MINITABLETS OF ENALAPRIL IN CHILDREN WITH HEART FAILURE DUE TO DILATED CARDIOMYOPATHY
• Scientific title: ORODISPERSIBLE MINITABLETS OF ENALAPRIL IN CHILDREN WITH HEART FAILURE DUE TO DILATED CARDIOMYOPATHY - ENADCM
• Date of first enrolment: 30/11/2015
• Target sample size: 50
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-002335-17
• 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
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Germany, 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 1 month to <12 years.
• Male and female patients.
• Diagnosis of DCM presenting with LV end-diastolic dimension >? P95 and/or LV shortening fraction (SF) • Subjects may be naïve to ACEI.
• Subjects already on ACEI willing to switch to enalapril Orodispersable Minitablets.
• Patient and/or parent(s)/legal representative provided written informed consent.

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

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:
• Severe HF and/or end stage heart failure requiring ICU support precluding introduction or continuation of ACEI.
• Too low blood pressure, e.g. ?P5
• Restrictive and hypertrophic cardiomyopathies.
• Obstructive valvular disease (peak echocardiographic gradient more than 30 mm Hg).
• Uncorrected severe peripheral stenosis of large arteries including severe coarctation of the aorta.
• Severe renal impairment with a GFR below 30 ml/1.73 m2 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 interventional trial with an investigational drug, unless no interference with current study can be shown.


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

Health Condition(s) or Problem(s) studied

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

Heart Failure due to Dilated Cardiomyopathy
MedDRA version: 18.1 Level: LLT Classification code 10056419 Term: Dilated cardiomyopathy System Organ Class: 100000004849

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)

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

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

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

Secondary Objective: 1. To demonstrate safety, in particular renal safety, of enalapril ODMTs in children with DCM.
2. To characterise the dose/safety relationship from a starting dose to an optimal maintenance dose.
3. To explore the dose exposure/response relationship with pharmacodynamic parameters in the paediatric population with DCM.
4. To investigate the Shortening Fraction (SF) of the heart muscle by echocardiography.
5. To investigate the acceptability and palatability of enalapril ODMTs in the paediatric population with DCM.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Biochemistry, Urine and BNP collected during each visit in the hospital to ensure 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.
Accepútability and Palatability questionnaire is completed during initial visit, once stable dose is reached and during end of study visit.

Secondary end point(s): 1. The bioavailability of enalapril and its active metabolite enalaprilat in the different age subsets (1 months to ?12 months, 12 months to ?6 years, 6 years to ?12 years) of the paediatric population (AUC from 0 to time of last sampling point, Cmax and Tmax); descriptive pharmacokinetic investigation.
2. Markers of the renin-angiotensin-aldosterone system as exploratory pharmacodynamic investigation.
3. Brain natriuretic peptides (BNPs).
4. Acceptability and palatability of the novel formulation.
5. Safety parameters including blood pressure and renal function.
6. Echocardiography (Shortening Fraction)
7. Rehospitalisation due to heart failure.
8. Death due to worsening of the underlying disease
9. Pharmacodynamic and efficacy endpoints analysis to differentiate high and low output disease

Secondary ID(s)

602295

2015-602295-01

Source(s) of Monetary Support

European Commission FP7 grant agreement 602295