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    The EU Clinical Trials Register currently displays   43974   clinical trials with a EudraCT protocol, of which   7312   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:2014-004897-40
    Sponsor's Protocol Code Number:GABA-2
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:
    Date on which this record was first entered in the EudraCT database:2017-05-11
    Trial 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 ConcernedFrance - ANSM
    A.2EudraCT number2014-004897-40
    A.3Full title of the trial
    Randomized, double-blind, placebo controlled, multi-centre, superiority phase II study to evaluate the safety, pharmacokinetic, efficacy of gabapentin liquid formulation as add-on to morphine in children from 3 months to less than 18 years of age experiencing severe chronic neuropathic or mixed pain.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Efficacy and safety study of gabapentin as add-on to morphine in paediatric patients affected by chronic severe pain
    A.3.2Name or abbreviated title of the trial where available
    Efficacy and safety study to compare gabapentin as add on to morphine in paediatric patients
    A.4.1Sponsor's protocol code numberGABA-2
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/250/2015
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorPHARM – Pharmaceutical Research Management srl
    B.1.3.4CountryItaly
    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 supportEuropean Commission – FP7-HEALTH-2013- INNOVATION-1 Grant Agreement n. 602962
    B.4.2CountryEuropean Union
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationPHARM – Pharmaceutical Research Management srl
    B.5.2Functional name of contact pointTrial Management
    B.5.3 Address:
    B.5.3.1Street AddressVia Einstein, Loc. Cascina Codazza
    B.5.3.2Town/ cityLodi
    B.5.3.3Post code26900
    B.5.3.4CountryItaly
    B.5.4Telephone number003903714662684
    B.5.5Fax number003903714662523
    B.5.6E-mailtrialmanagement@pharmsrl.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 No
    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 namegabapentin
    D.3.4Pharmaceutical form Syrup
    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 INNgabapentin hydrochloride
    D.3.9.1CAS number 60142-95-2
    D.3.9.2Current sponsor codenot applicable
    D.3.9.3Other descriptive nameGABAPENTIN HYDROCHLORIDE
    D.3.9.4EV Substance CodeSUB126895
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number75
    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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSyrup
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Chronic pain of neuropathic or mixed origin
    E.1.1.1Medical condition in easily understood language
    Chronic pain
    E.1.1.2Therapeutic area Diseases [C] - Nervous System Diseases [C10]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10054095
    E.1.2Term Neuropathic pain
    E.1.2System Organ Class 100000004852
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    to evaluate the efficacy of gabapentin as adjunctive therapy to morphine in the treatment of severe chronic neuropathic or mixed pain in children from 3 months to less than 18 years of age assessed by the difference in average pain scores between treatment arms at the end of the treatment period.
    E.2.2Secondary objectives of the trial
    1.To assess the effect of gabapentin as adjunctive therapy to morphine compared to morphine alone on quality of life (physical, emotional, social and school functioning) and global satisfaction with treatment.
    2.To assess the safety of gabapentin combined with morphine compared to morphine alone in the treatment of severe neuropathic or mixed pain in children from 3 months to less than 18 years of age.
    3.To characterise the population pharmacokinetic-pharmacodynamic (PKPD) relationship of gabapentin liquid formulation with and without morphine and provide confirmation of the recommended paediatric dose.
    Additional exploratory objectives of the study are:
    4.To explore the metabolomic profile of drug treatments.
    5.To explore genetic polymorphisms and their impact on pharmacokinetics (PK) and pharmacodynamics (PD).
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1.Male or female, aged 3 months to less than 18 years at screening (V1)
    2.Informed consent by parent(s) and/or legal guardian according to each country legal requirement.
    3.Assent, where applicable, according to each country legal requirement.Informed (co-) consent of child, where applicable, according to each country legal requirement.
    4.Subjects that meet the diagnostic criteria for neuropathic or mixed pain.
    5.Subjects that present with chronic pain defined as the recurrent or continuous pain persisting more than 3 months.
    6.Subject that present with severe pain as defined by average pain intensity of ≥7 /10 as assessed during a 3-day screening period
    7.Stable underlying disease condition and treatment.
    8.Patients with Chemotherapy Induced Peripheral Neuropathy, when in clinical remission or maintenance phase of their therapeutic protocol.
    E.4Principal exclusion criteria
    1.Pain duration of more than 5 years.
    2.Current use of gabapentin.
    3.Current use of strong opioids (morphine, methadone, fentanyl, ketamine, oxycodone).
    4.History of failure to respond to adequate treatment by gabapentin or opioids for neuropathic pain.
    5.History of epileptic condition (except febrile seizure disorder).
    6.Subjects with diagnosis of sickle cell disease.
    7.Subjects that present significant cognitive impairment.
    8.Subjects that present current, controlled or uncontrolled, co-morbid psychiatric diagnosis that can impair pain diagnosis and assessment such as severe depressive conditions or psychosis.
    9.Subjects with history of or current suicidal ideation or behaviour.
    10.Subjects with history of substance abuse in particular opioids.
    11.Subjects under prohibited concomitant medication .
    12.Subjects with a body mass index (BMI) for age and gender of < 5th percentile or > 95th percentile (charts provided as Appendix 3).
    13.Subjects with significant renal impairment, i.e., glomerular filtration rate < 90 mL/min/1.73 m2 (Revised Schwarz equation).
    14.Subjects with significant hepatic impairment or with Aspartate Transaminase (AST) or Alanine Transaminase (ALT) enzymes 3 times the upper limit of the age-specific reference range.
    15.Subjects in need for corticosteroid oral treatment or corticosteroid infiltrations to treat pain caused by infiltration or compression of neural structures, e.g. peripheral nerves or spinal cord.
    16.Subjects with clinically relevant abnormal ECG at the screening visit in the discretion of the Investigator/cardiologist.
    17.Subjects with known allergy, hypersensibility or clinically significant intolerance to gabapentin or any component found in the study drugs.
    18.Subjects with fructose intolerance, diabetes, glucose-galactose malabsorption or lactase-isomaltase deficiency.
    19.Subjects participating in another clinical interventional trial.
    20.Subjects scheduled for surgery or in recovery from surgery occurring within 3 months of baseline assessment.
    21.Female subjects who are pregnant or currently lactating.
    22.Subjects that failed screening or were previously enrolled in this study
    23.Patients with Chemotherapy Induced Peripheral Neuropathy, when in induction phase of their therapeutic protocol.
    E.5 End points
    E.5.1Primary end point(s)
    Average pain scores in the two treatment groups (average of 2 measures each day for 3 days before end of study visit V10) assessed by age-appropriate pain scales (FLACC. FPS-R, NRS-11).
    E.5.1.1Timepoint(s) of evaluation of this end point
    Baseline, End of study
    E.5.2Secondary end point(s)
    a) Percentage of responders to treatments, defined as subjects with a 30% reduction from baseline in assessment scale (FLACC, FPS-R, NRS-11).
    b) Average daily pain intensity, assessed by age appropriate scale (FLACC, FPS-R or NRS-11) during dose optimization.
    c) Observational assessment of pain using the NRS-11 completed by parents and Investigator (or caregiver) at each visit.
    d) Self-assessment of pain for children ≥8 years of age using the FPS-R pain scale at each visit.
    e) Extent of pain evaluated as the number of painful areas using the pain charts at screening visit (V1), randomisation (v2) and EOS visit (V10).
    f) Number of episodes of breakthrough pain (>7/10 pain score and use of rescue medications) during treatment period.
    g) Number of rescue interventions required during treatment period.
    h) Number of pain-free days (<4/10 average pain score without the use of rescue medications) during treatment period.
    i) Participant dropouts due to lack of adequate pain response.
    j) The total cumulative weight normalized dose of each rescue drug.
    k) Quality of life, physical, emotional, social and school functioning and quality of sleep on the PedsQL Generic Core Scales (by parent, patient) assessed at randomisation (V2) and at EOS (V10).
    l) Acceptability of treatment (Five Point Facial Hedonic Scale) at EOS visit (V10).
    m) Global satisfaction with treatment (NRS-11, by parent, patient) at EOS visit (V10).
    n) Clinical Global Impression of Change (CGI-S, CGI-I; by Investigator) at randomization (V2) for CGI-S and V6 and EOS visit (V10) for CGI-I.
    o) Patient/parent Global Impression of Change (PGIC; by parent, patient) at V6 and EOS visit (V10).
    p) Primary (CL/F, Vd/F, Ka) and secondary (AUC, Cmax, Tmax, Css and Cmin) pharmacokinetic parameters for gabapentin.
    q) Systemic exposure to investigational product during maintenance period, as assessed by predicted steady-state concentrations.
    r) Incidence of Adverse Events at all visits.
    s) Percentage of subjects discontinuing the Trial due to treatment-emergent adverse events.
    t) Aggressive behaviour in children aged >6 years using the Retrospective Modified Overt Aggression Scale (R-MOAS) at V2, V6 and EOS visit (V10).
    u) Suicidal ideation/behaviour in subjects aged 6 years and older using the Columbia - Suicide Severity Rating Scale (C-SSRS) scores before IMP (screening V1), V6, EOS visit (V10) and taper visit (V11).
    v) Assessment of blinding: guess of the subject’s treatment group (by Investigator, parents and subject if at adequate maturity level) at V10.
    E.5.2.1Timepoint(s) of evaluation of this end point
    a) Baseline, end of study
    b) Daily during dose optimisation
    c) Monthly
    d) Monthly
    e) Daily during treatment period
    f) Daily during treatment period.
    g) Daily during treatment period.
    h) Daily during treatment period
    i) End of study
    j) End of study
    k) Randomisation, end of study
    l) End of study
    m) End of study
    n) Randomisation, end of optimisation phase, end of study
    o) End of optimisation phase, end of study
    p) Sparse sampling during study or end of study
    q) Sparse sampling during study or end of study
    r) Monthly
    s) End of study
    t) Randomisation, end of optimisation phase, end of study
    u) Screening, End of optimisation phase, end of study, end of taper
    v) End of study
    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 Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Metabolomic
    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 Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    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 concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA11
    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
    Albania
    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 years1
    E.8.9.1In the Member State concerned months8
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months8
    E.8.9.2In all countries concerned by the trial days0
    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: 66
    F.1.1.1In Utero No
    F.1.1.1.1Number of subjects for this age range: 0
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.2.1Number of subjects for this age range: 0
    F.1.1.3Newborns (0-27 days) No
    F.1.1.3.1Number of subjects for this age range: 0
    F.1.1.4Infants and toddlers (28 days-23 months) Yes
    F.1.1.4.1Number of subjects for this age range: 4
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 31
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 31
    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 Yes
    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
    Paediatric population
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state15
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 61
    F.4.2.2In the whole clinical trial 66
    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)
    In accordance with the Declaration of Helsinki, subjects who still require analgesic treatment after the study period will
    be treated with the standard of care practices of the local site and national guidelines
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation Teddy Network
    G.4.3.4Network Country Italy
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2017-05-02
    N.Ethics Committee Opinion of the trial application
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion
    P. End of Trial
    P.End of Trial Status
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