Orodispersible Minitablets of Enalapril in Children With Heart Failure Due to Dilated Cardiomyopathy

NCT02652728 | Unknown Phase 2 DMC

• 2 other identifiers: 2015-602295-012015-002335-17
• Study Type: interventional
• Target: 50
• Locations: 5 countries
• Sites: 6

Brief Summary

Paediatric clinical trial in 50 children, from 1 month to less than 12 years of age, suffering from heart failure due to dilated cardiomyopathy, 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; Dilated Cardiomyopathy

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 bioavailability of enalapril ODMTs in children with heart failure due to dilated cardiomyopathy (1 month to less than 12 years); descriptive pharmacokinetic investigation

  0 hours to 12 hours

• Maximum Concentration (Cmax) of enalapril and its active metabolite enalaprilat after administration of enalapril ODMTs in children with heart failure

  Maximum Concentration (Cmax) of enalapril and enalaprilat are measured at first dose or any time during steady state to assess bioavailability of enalapril ODMTs in children with heart failure due to dilated cardiomyopathy (1 month to less than 12 years); descriptive pharmacokinetic investigation

  0 hours to 12 hours

• Time to Maximum Concentration (Tmax) of enalapril and its active metabolite enalaprilat after administration of enalapril ODMTs in children with heart failure

  Time to Maximum Concentration (Tmax) of enalapril and enalaprilat are measured at first dose or any time during steady state to assess bioavailability of enalapril ODMTs in children with heart failure due to dilated cardiomyopathy (1 month to less than 12 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 children with heart failure of two age-subsets

  0 hours to 12 hours

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

  0 hours to 12 hours

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

  0 hours to 12 hours

• Renin

  Pre-dose, 4 h post first dose, pre-dose at each Titration Visit and Study Control Visit (day 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 (day 14, 28, 42) up to Last Visit after 8 (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

Weight-dependent dose titration and long-term treatment scheme with enalapril ODMTs of 0.25 mg and 1 mg strength

Also known as: Enalapril ODMT

Drug administration

Eligibility Criteria

• Age: 1 Month - 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Patients presenting with heart failure with signs of left ventricular (LV) systolic dysfunction who are eligible to receive ACE-Inhibitors in addition to standard therapy (e.g., digitalis and diuretics) can be enrolled into this trial. Patients who previously presented with LV systolic dysfunction and who have already been treated with ACE-Inhibitors, and currently still have an indication for the use of an ACE-Inhibitor can be switched to an equivalent starting dose of enalapril ODMT.
• Age 1 month to less than 12 years.
• Male and female patients.
• Diagnosis of dilated cardiomyopathy presenting with LV end-diastolic dimension \> P95 and/or LV shortening fraction (SF) \< 25%
• Subjects may be naïve to ACE-Inhibitor.
• Subjects already on ACE-Inhibitor willing to switch to enalapril Orodispersible Minitablets.
• Written informed consent from parent(s)/legal representative and assent from the patient according to national legislation and as far as achievable from the child.

You may not qualify if:

• Severe heart failure and/or end stage heart failure precluding introduction or continuation of ACE-Inhibitor.
• 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 serum creatinine \>2x Upper Limit of Normal (ULN) (according to the hospital's test methodology).
• History of angioedema.
• Hypersensitivity to ACE-Inhibitor.
• Concomitant 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; Cardiomyopathy, Dilated

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Cardiomegaly; Cardiomyopathies; Laminopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Michiel Dalinghaus, MD, PhD

  Sophia Children's Hospital Erasmus MC Rotterdam

  STUDY CHAIR

• J.M.P. J. Breur, MD, PhD

  Wilhelmina Children's Hosptial University Medical Center Utrecht

  PRINCIPAL INVESTIGATOR

• Ida Jovanovic, Prof,MD,PhD

  Univerzitetska Decja Klinika Belgrade

  PRINCIPAL INVESTIGATOR

• Christoph Male, Prof, MD,PhD

  Medical University of Vienna

  PRINCIPAL INVESTIGATOR

• Michael Burch, Prof,MD,PhD

  Great Ormond Street Hospital for Children London

  PRINCIPAL INVESTIGATOR

• András Szatmári, Prof,MD,PhD

  Hungarian Paediatric Heart Institute, 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 7843692; 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 3, 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

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