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    The EU Clinical Trials Register currently displays   43857   clinical trials with a EudraCT protocol, of which   7284   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    Summary
    EudraCT Number:2014-000623-24
    Sponsor's Protocol Code Number:KF5503-72
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2014-08-04
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedUK - MHRA
    A.2EudraCT number2014-000623-24
    A.3Full title of the trial
    Open-label evaluation of the population pharmacokinetic profile, safety, tolerability, and efficacy of tapentadol oral solution for the treatment of post-surgical pain in children aged from birth to less than 2 years.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Use of tapentadol oral solution for pain after surgery in children from newborn to less than 2 years old.
    A.3.2Name or abbreviated title of the trial where available
    Use of tapentadol oral solution for pain after surgery in children from newborn to less than 2 years
    A.4.1Sponsor's protocol code numberKF5503-72
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02221674
    A.5.3WHO Universal Trial Reference Number (UTRN)U1111-1153-1662
    A.5.4Other Identifiers
    Name:R331333PAI2007Number:Depomed Inc.
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/279/2013
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorGrünenthal GmbH
    B.1.3.4CountryGermany
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportGrünenthal GmbH
    B.4.2CountryGermany
    B.4.1Name of organisation providing supportDepomed Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationGrünenthal GmbH
    B.5.2Functional name of contact pointGrünenthal Trial Information Desk
    B.5.3 Address:
    B.5.3.1Street AddressZieglerstr. 6
    B.5.3.2Town/ cityAachen
    B.5.3.3Post code52078
    B.5.3.4CountryGermany
    B.5.4Telephone number49241569 3223
    B.5.6E-mailClinical-Trials@grunenthal.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Palexia 4 mg/mL Lösung zum Einnehmen
    D.2.1.1.2Name of the Marketing Authorisation holderGrünenthal GmbH
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameTapentadol 4 mg/mL Oral Solution
    D.3.2Product code CG5503
    D.3.4Pharmaceutical form Oral solution
    D.3.4.1Specific paediatric formulation Yes
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTapentadol
    D.3.9.1CAS number 175591-09-0
    D.3.9.2Current sponsor codeCG5503
    D.3.9.3Other descriptive nameTAPENTADOL HYDROCHLORIDE
    D.3.9.4EV Substance CodeSUB32145
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number4
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Moderate to severe acute post-operative pain.
    E.1.1.1Medical condition in easily understood language
    Acute post-operative pain
    E.1.1.2Therapeutic area Diseases [C] - Symptoms and general pathology [C23]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of the trial is to collect serum concentration data of tapentadol and its major metabolite tapentadol-O-glucuronide after the administration of a single dose of tapentadol oral solution in children aged from birth to less than 2 years after a surgical procedure that routinely produces moderate to severe acute post-surgical pain requiring opioid treatment. The concentration data will be used to characterize the pharmacokinetic parameters of tapentadol using a population and physiologically-based pharmacokinetic approach. This will enable data based recommendations for the use of tapentadol in children of different ages (birth to less than 1 month, 1 month to less than 6 months, and
    6 months to less than 2 years) in subsequent safety and efficacy trials.
    E.2.2Secondary objectives of the trial
    To evaluate the safety and tolerability of tapentadol oral solution in the population studied.
    To explore the effect of tapentadol oral solution on moderate to severe pain that, in the opinion of the investigator, requires treatment with an opioid.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    • The participant's parent(s) or legal guardian(s) have given written informed consent to participate.
    • Participant is not obese (e.g., a body weight above the 97th percentile for children based on the World Health Organization weight charts) with a minimum body weight of 2.5 kg.
    • Physical status rated not higher than P3 on the American Society of Anesthesiologists physical status classification in subjects aged from 1 month to less than 2 years.
    • Participant has undergone surgery that, in the investigator's opinion, would reliably produce moderate to severe pain requiring opioid treatment.
    • At the time of allocation to study medication, particiapnt has a sedation score that is not higher than 2 (moderately sedated) on the University of Michigan Sedation Scale and subject is able to tolerate oral medication and oral fluids.
    • Participant has a reliable venous vascular access for pharmacokinetic blood sampling.
    E.4Principal exclusion criteria
    • The participant's parent(s) or legal guardian(s) is an employee of the investigator or trial site, with direct involvement in this trial or other trials under the direction of that investigator or trial site, or the subject, or subject's parent(s), or legal guardian(s) is a family member of the employees or the investigator.
    • Participant has been previously exposed to tapentadol.
    • Participant has received an experimental drug or used an experimental medical device within 28 days before allocation to study medication, or within a period less than 10 times the drug's half-life, whichever is longer.
    • Concomitant participation in another clinical trial with an experimental drug or experimental device for the duration of this trial.
    • Participant has undergone brain surgery.
    • Participant has undergone a surgery that is expected to affect the absorption of tapentadol (e.g., to the gastrointestinal tract).
    • Participant has a history or current condition of any one of the following:
    - Seizure disorder.
    - Traumatic or hypoxic brain injury, brain contusion, stroke, transient ischemic attack, intracranial hematoma, post-traumatic amnesia, brain neoplasm, or episode(s) of unconsciousness of more than 24 hours.
    • Participant has a history or current condition of any one of the following:
    - Moderate to severe renal impairment.
    - Moderate to severe hepatic impairment, congestive hepatopathy, or hepatic portosystemic shunting.
    - Clinically relevant abnormal pulmonary function or clinically relevant respiratory disease.
    • Participant has signs or symptoms of congestive heart failure (e.g., requiring more than minimal inotropic support, an abnormal lactic acid value greater than 2-times upper limit of normal), or hemorrhagic disorder following surgery.
    • Minimal inotropic medication is defined as:
    - Dopamine less or equal to 5 microgram/kg per minute.
    - Epinephrine less or equal to 0.03 microgram/kg per minute (but not both dopamine and epinephrine).
    - Milrinone less or equal to 0.5 microgram/kg per minute or less.
    • Participant has a concomitant disease or disorder (e.g., endocrine, metabolic, neurological, or psychiatric disorder, or a febrile seizure or paralytic ileus) that in the opinion of the investigator may affect or compromise participant's safety during the trial participation.
    • Participant has cognitive or developmental impairment such that trial participation may affect or compromise the participant's safety, or the participant's ability to comply with the protocol requirements (as appropriate for the subject's age), in the investigator's judgment. Otherwise, participant's with cognitive or developmental impairment may be enrolled in the trial.
    • Participant has a clinically relevant history of hypersensitivity, allergy, or contraindication to tapentadol (or ingredients).

    Participant has:
    • Clinically relevant abnormal 12-lead ECG.
    • Signs of pre-excitation syndrome.
    • Corrected QT (QTcF) interval >460 ms. Subjects may be allocated to IMP with values >460 ms if, in the investigator’s opinion, the value is a consequence of cardiac surgery and is not considered clinically significant.
    • Participant has clinically relevant abnormal lab values from a sample obtained postoperatively and prior to allocation to study medication. The following specifications will apply:
    - Aspartate transaminase or alanine transaminase is greater than 2.5-times upper limit of normal.
    - Total bilirubin is greater than 2-times upper limit of normal and direct bilirubin is greater than 20% of the total bilirubin.
    - Glomerular filtration rate (calculated according to Schwartz et al. 1984, Schwartz et al. 2009, Schwartz and Work 2009)
    - less than 20 mL/min/1.73 m2 for participants less than 1 week old.
    - less than 30 mL/min/1.73 m2 for participants 1 week to 8 weeks old.
    - less than 50 mL/min/1.73 m2 for participants more than 8 weeks old.
    • Signs or symptoms indicative of a systemic infection within 24 hours prior to allocation to IMP, in the investigator’s judgment.
    • Participant has been administered a prohibited medication.
    • The mother of a newborn participant or the breastfeeding mother of a participant was administered a prohibited medication (see Restrictions for the mother of a newborn or breastfeeding mother).
    • Participant has post-operative, clinically unstable systolic and diastolic blood pressure, heart rate, respiratory depression, or clinically unstable upper or lower airway conditions.
    • Participant has a peripheral oxygen saturation (SpO2) <92% for acyanotic subjects, or <75% for cyanotic subjects, with or without supplemental oxygen via nasal cannula or high flow nasal cannula, at the time of allocation to IMP.
    • Participant requires continuous positive airway pressure or mechanical ventilation, at the time of allocation to IMP.
    E.5 End points
    E.5.1Primary end point(s)
    Pharmacokinetic evaluation based on serum concentrations of tapentadol and tapentadol-O-glucuronide obtained from blood samples.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Within 8 hours of study medication intake at 2 time points per participant.
    E.5.2Secondary end point(s)
    None
    E.5.2.1Timepoint(s) of evaluation of this end point
    Not applicable
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    staggered sequential dosing by participant age.
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial1
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned2
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Poland
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months12
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial months12
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 15
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) Yes
    F.1.1.3.1Number of subjects for this age range: 5
    F.1.1.4Infants and toddlers (28 days-23 months) Yes
    F.1.1.4.1Number of subjects for this age range: 10
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) No
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Minors incapable of giving consent.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state5
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 5
    F.4.2.2In the whole clinical trial 15
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Standard of care
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2014-08-28
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2014-10-30
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2016-12-14
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