Orodispersible Minitablets of Enalapril in Young Children With Heart Failure Due to Congenital Heart Disease

NCT02652741 | Unknown Phase 2 DMC

• 2 other identifiers: 2015-602295-022015-002396-18
• Study Type: interventional
• Target: 50
• Locations: 5 countries
• Sites: 6

Brief Summary

Paediatric clinical trial in 50 children, from newborn to less than 6 years of age, suffering from heart failure due to congenital heart disease, to obtain paediatric pharmacokinetic and pharmacodynamic data of enalapril and its active metabolite enalaprilat while treated for 8 weeks with enalapril in form of Orodispersible Minitablets (ODMTs), to describe the dose exposure in this patient population.

Conditions

Heart Failure; Congenital Heart Disease

Outcome Measures

Primary Outcomes (3)

• Area under the Curve (AUC) of enalapril and its active metabolite enalaprilat after administration of enalapril ODMTs in children with heart failure

  Area under the Curve (AUC) of enalapril and enalaprilat are measured at first dose or at any time during steady state to assess the bioavailability of enalapril ODMTs in young children with heart failure due to congenital heart disease (newborn to less than 6 years); descriptive pharmacokinetic investigation

  0 hours to 12 hours

• Maximum Concentration (Cmax) of enalapril and its active metabolite

  Maximum Concentration (Cmax) of enalapril and enalaprilat are measured at first dose or any time during steady state to assess the bioavailability of enalapril ODMTs in young children with heart failure due to congenital heart disease (newborn to less than 6 years); descriptive pharmacokinetic investigation

  0 hours to 12 hours

• Time to Maximum Concentration (Tmax) of enalapril and its active metabolite

  Time to Maximum Concentration (Tmax) of enalapril and enalaprilat are measured at first dose or any time during steady state to assess the bioavailability of enalapril ODMTs in young children with heart failure due to congenital heart disease (newborn to less than 6 years); descriptive pharmacokinetic investigation

  0 hours to 12 hours

Secondary Outcomes (18)

• AUC of enalapril and its active metabolite enalaprilat after administration of enalapril ODMTs in two age-subsets of children with heart failure

  0 hours to 12 hours

• Cmax of enalapril and its active metabolite enalaprilat after administration of enalapril ODMTs in two age-subsets of children with heart failure

  0 hours to 12 hours

• Tmax of enalapril and its active metabolite enalaprilat after administration of enalapril ODMTs in two age-subsets of children with heart failure

  0 hours to 12 hours

• Renin

  Pre-dose, 4 h post first dose, pre-dose at each Titration Visit and Study Control Visit (days 14, 28, 42) up to Last Visit (day 56)

• Angiotensin 1

  Pre-dose, 4 h post first dose, pre-dose at each Titration Visit and Study Control Visit (days 14, 28, 42) up to Last Visit (day 56)

Study Arms (1)

Drug administration

EXPERIMENTAL

Enalapril Orodispersible Minitablet (ODMT), 0.25 mg or 1 mg, administered 1x/day or 2x/day for up to 8 weeks

Drug: Enalapril Orodispersible Minitablet

Interventions

Enalapril Orodispersible Minitablet DRUG

8-weeks treatment, open, uncontrolled, PK/PD, acceptability and palatability assessments and safety assessments after Enalapril intake in form of 0.25 mg or 1 mg ODMTs

Also known as: Enalapril ODMT

Drug administration

Eligibility Criteria

• Age: 1 Day - 5 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.
• Subjects already on ACE-Inhibitors willing to switch to enalapril Orodispersible Minitablets.
• Patient and/or parent(s)/legal representative provided written informed consent and assent from the patient according to national legislation and as far as achievable from the child.

You may not qualify if:

• Neonates if born \< 37 weeks of gestation.
• Severe heart failure and/or end stage heart failure precluding introduction or continuation of ACE-Inhibitor.
• Too low blood pressure, e.g. ˂P5
• 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 Upper Limit of Normal (ULN) (according to the hospital's test methodology)
• History of angioedema.
• Hypersensitivity to ACE-Inhibitors.
• Concommitant medication:
• Dual ACE-Inhibitor therapy
• Renin inhibitors
• Angiotensin II antagonists
• Non-Steroidal Anti-Inflammatory Drugs (including ibuprofen) except for aspirin and paracetamol
• Already enrolled in an interventional trial with an investigational drug, unless no interference with the current study can be shown.

Sponsors & Collaborators

• Ethicare GmbH: lead

Study Sites (6)

Medical University of Vienna

Vienna, 1090, Austria

Location

Hungarian Paediatric Heart Centre, Göttsegen Gyorgy Hungarian Institute of Cardiology

Budapest, 1095, Hungary

Location

Sophia Children's Hospital, Erasmus MC

Rotterdam, 3015 CN, Netherlands

Location

Wilhelmina Children's Hospital, University Medical Center Utrecht

Utrecht, 3584 CX, Netherlands

Location

Univerzitetska Dečja Klinika

Belgrade, 11129, Serbia

Location

Great Ormond Street Hospital for Children NHS Trust

London, WC1N 3JH, United Kingdom

Location

MeSH Terms

Conditions

Heart Failure; Heart Defects, Congenital

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Cardiovascular Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Milica Bajcetic, Prof,MD,PhD

  Univerzitetska Dečja Klinika Belgrade

  STUDY CHAIR

• Ida Jovanovic, Prof,MD,PhD

  Univerzitetska Dečja Klinika Belgrade

  PRINCIPAL INVESTIGATOR

• Michiel Dalinghaus, MD,PhD

  Sophia Children's Hospital, Erasmus MC Rotterdam

  PRINCIPAL INVESTIGATOR

• J.M.P. J Breur, MD,PhD

  Wilhelmina Children's Hospital, University Medical Center Utrecht

  PRINCIPAL INVESTIGATOR

• Christoph Male, Prof,MD,PhD

  Medical University of Vienna

  PRINCIPAL INVESTIGATOR

• Michael Burch, Prof,MD,PhD

  Great Ormond Street Hospital for Children NHS Trust London

  PRINCIPAL INVESTIGATOR

• András Szatmári, Prof,MD,PhD

  Hungarian Paediatric Heart Centre, Göttsegen Gyorgy Hungarian Institute of Cardiology Budapest

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stephanie Laeer, Prof,MD,PhD

CONTACT

+49 211 8110740; stephanie.laeer@uni-duesseldorf.de

Ingrid Klingmann, MD,PhD

CONTACT

+32 2 784 36 93; iklingmann@pharmaplex.be

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2016
• First Posted: January 12, 2016
• Study Start: January 1, 2016
• Primary Completion: June 1, 2017
• Study Completion: June 1, 2017
• Last Updated: January 12, 2016

Record last verified: 2016-01

Data Sharing

• IPD Sharing: Will share

Locations

SE (1); AU (1); HU (1); GB (1); NL (2)