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    The EU Clinical Trials Register currently displays   43871   clinical trials with a EudraCT protocol, of which   7290   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:2010-021955-14
    Sponsor's Protocol Code Number:BUP3030
    National Competent Authority:Hungary - National Institute of Pharmacy
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2011-09-07
    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 ConcernedHungary - National Institute of Pharmacy
    A.2EudraCT number2010-021955-14
    A.3Full title of the trial
    A Multicenter, Inpatient, Open-label Study to Characterize the Pharmacokinetics,
    Safety, and Efficacy of Intravenous Dosing of Buprenorphine in Pediatric Patients Aged from Birth to 6 Years of Age (inclusive) Who Require Opioid Analgesia for Acute Moderate to Severe Pain
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study of the body distribution, safety, and effectiveness of buprenorphine given by vein in children from birth to 6 years of age who require opioids for moderate to severe pain
    A.4.1Sponsor's protocol code numberBUP3030
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT01324544
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorPurdue Pharma L.P.
    B.1.3.4CountryUnited States
    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 supportPurdue Pharma L.P.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationPRA International
    B.5.2Functional name of contact pointPurdue Pediatric Call Centre
    B.5.3 Address:
    B.5.3.1Street AddressGlen Lake 6, 4130 Parklake Avenue, Suite 400.
    B.5.3.2Town/ cityRaleigh, NC
    B.5.3.3Post code27612
    B.5.3.4CountryUnited States
    B.5.4Telephone number+14349514115
    B.5.5Fax number+19135992753
    B.5.6E-mailPurduePediatric@praintl.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 nameBuprenex
    D.3.4Pharmaceutical form Injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 53152-21-9
    D.3.9.3Other descriptive nameBUPRENORPHINE HYDROCHLORIDE
    D.3.9.4EV Substance CodeSUB13133MIG
    D.3.10 Strength
    D.3.10.1Concentration unit µg/ml microgram(s)/millilitre
    D.3.10.2Concentration typeup to
    D.3.10.3Concentration number100
    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
    Acute moderate to severe pain requiring opioids for at least 24 hours in postoperative and prolonged endotracheal intubated patients
    E.1.1.1Medical condition in easily understood language
    Moderate to severe 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 14.0
    E.1.2Level LLT
    E.1.2Classification code 10002182
    E.1.2Term Analgesia
    E.1.2System Organ Class 10042613 - Surgical and medical procedures
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.0
    E.1.2Level LLT
    E.1.2Classification code 10021415
    E.1.2Term Immediate postoperative analgesia
    E.1.2System Organ Class 10042613 - Surgical and medical procedures
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To characterize the safety, PK, and efficacy of IV buprenorphine in pediatric patients
    aged from birth to up to 6 years of age, inclusive.
    E.2.2Secondary objectives of the trial
    N/A
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Must have written informed consent provided by the parent or legal guardian and/or patient assent, when appropriate
    2. Male and female children, from birth to aged 6 years, inclusive, with minimum weight of 2.5 kg
    3. Have or are anticipated to have acute moderate to severe pain; requiring treatment with an IV opioid analgesic medication for at least 24 hours postoperatively or; due to
    prolonged endotracheal intubation requiring IV opioid analgesic treatment for at least 24 hours poststabilization
    4. Must have stable vital signs
    5. Must have stable respiratory status
    6. Must have the following:
    a. A normal respiratory rate for age
    b. Sustained pulse oximetry (SpO2) ≥ 92%
    c. No significant (grade 3 or 4) somnolence based on the University of Michigan Sedation Scale (UMSS) and the investigator’s judgment
    7. Prolonged intubated patients must be stabilized on an opioid (standard of care) infusion other than buprenorphine
    8. Patients with cystic fibrosis resulting in persistent chest pain must have been treated with opioid analgesics up to the screening visit and have tolerated the therapy
    9. Must be inpatient for the treatment period of the study
    10. Must have 3 conventional 12-lead ECGs, a minimum of 10 minutes apart, after any surgery and before study drug treatment, with the average value of QTcB and QTcF of the 3 tracings < 460 msec
    11. Must have 24-hour digital ECGs (Holter Monitor), before study drug treatment, with the value of QTcB and QTcF < 460 msec
    12. Must have serum potassium, calcium, and magnesium levels within the reference range for age (defined by the testing laboratory)
    13. Must be able to use the age appropriate pain scales
    14. Must have vascular access to facilitate blood draws.
    E.4Principal exclusion criteria
    1. Have any known allergy or sensitivity to buprenorphine or other opioids (this criterion does not include patients who have experienced common opioid side effects [eg, nausea, constipation])
    2. Have evidence of impaired renal function (serum creatinine > 2 times the upper limit of normal [ULN] for age)
    3. Have hepatic impairment as evidenced by serum alanine transaminase (ALT/SGPT) or
    serum aspartate transaminase (AST/SGOT) > 5 times the ULN for age
    4. Have any history of seizures (with the exception of patients with history of pediatric febrile seizures)
    5. Have biliary tract disease, hypothyroidism, adrenal cortical insufficiency, or any other medical condition that, in the investigator’s opinion, was inadequately treated and precluded entry into the study
    6. Have any contraindication to blood sampling
    7. Have received epidural anesthesia < 12 hours prior to the first dose of study drug
    8. Are cyanotic
    9. Have a history of sleep apnea within the past year
    10. Have structural heart disease or a pacemaker
    11. Have syncope, near syncope, or palpitations requiring further investigations
    12. Have clinically unstable cardiac disease including but not limited to: unstable congestive heart failure or active myocardial ischemia
    13. Have either short (QTc less than 340 msec) or long QT Syndrome or inherited
    arrhythmia (including but not limited to: Brugada Syndrome, Catecholaminergic
    Polymorphic Ventricular Tachycardia [CPVT], or Arrhythmogenic Right Ventricular
    Dysplasia [ARVD]) or any family member with these conditions;
    14. Have the following conventional 12-lead ECG findings of any supraventricular
    arrhythmias (history or current) or any ventricular arrhythmias (history or current) except patients with single isolated monomorphic premature atrial contractions, premature junctional contractions, or premature ventricular contractions that occur less than 42
    times per hour (< 1,000 times per 24 hours) based on 24-hour digital ECG (Holter Monitor); QRS duration > 80 msec (intraventricular conduction delay); definite left or right ventricular hypertrophy based on voltage and repolarization measurements by age standard; amplitude of U wave 25% greater than that of T wave or inverted U wave in leads V1 to V5; 1st degree atrioventricular (AV) block by age standard (P-R interval > 140
    msec); suspicion of pre-excitation syndrome; 2nd degree AV block (Mobitz I); 2nd degree AV block (Mobitz II); 3rd degree AV block; atrial flutter; atrial fibrillation; marked sinus bradycardia by age standard (HR < 80 bpm for patients aged from birth to 3 years, inclusive; HR < 60 bpm for patients aged 4 to 6 years, inclusive); or sinus tachycardia by
    age standard (HR > 180 bpm for patients aged from birth to 3 years, inclusive; HR > 150 bpm for patients aged 4 to 6 years, inclusive)
    15. Have the following 24-hour digital ECG (Holter Monitor) findings of any supraventricular arrhythmias or any ventricular arrhythmias except patients with single isolated monomorphic premature atrial contractions, premature junctional contractions, or
    premature ventricular contractions that occur less than 42 times per hour (< 1,000 times per 24 hours); QRS duration > 80 msec (intraventricular conduction delay); 1st degree atrioventricular (AV) block by age standard (P-R interval > 140 msec); suspicion of pre-excitation syndrome; 2nd degree AV block (Mobitz I); 2nd degree AV block (Mobitz II); 3rd degree AV block; atrial flutter; atrial fibrillation; or marked sinus bradycardia by age standard (HR < 80 bpm for patients aged from birth to 3 years, inclusive; HR < 60 bpm for patients aged 4 to 6 years, inclusive);1, 2
    16. Have other clinically significant abnormal findings demonstrated on conventional 12-lead ECG that, in the investigator’s opinion, preclude the patient’s entry into this study
    17. Have other clinically significant abnormal findings demonstrated on 24-hour digital ECGs (Holter Monitor) that, in the investigator’s opinion, preclude the patient’s entry into this study
    18. Have received Class IA antiarrhythmic medications (eg, quinidine, procainamide,
    disopyramide) or Class III antiarrhythmic medications (eg, sotalol, amiodarone,
    dofetilide); within the last 7 days prior to the initial study drug dose and/or will require such medications during study treatment
    19. Have received medications that inhibit CYP450 3A4 enzymes within the last 7 days prior to the initial study drug dose and/or will require such medications during study treatment
    20. Have received medications that have the potential of prolonging QT interval within the last 7 days prior to the initial study drug dose and/or will require such medications during study treatment
    21. Have used any investigational medication/therapy within 30 days prior to the first dose of study drug
    22. Are deemed to be unsuitable by the investigator for reason(s) not specifically stated in the exclusion criteria.
    E.5 End points
    E.5.1Primary end point(s)
    Safety Variables: Physical examinations will be performed during the screening period and at end of study.
    Vital signs (blood pressure, pulse rate, respiratory rate, and temperature), SpO2, ECGs, reports of AEs, and somnolence using the UMSS, will be obtained at specified time intervals during the study. Clinical laboratory tests, including hepatic enzymes (alanine aminotransferase and aspartate aminotransferase), bilirubin,
    creatinine, blood urea nitrogen and complete blood count with differential will be obtained before initial administration of study drug and at end of study. Safety parameters will be closely monitored throughout the study.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Safety variables will be summarized descriptively within each age group for the safety population. Safety assessments to be summarized include reports of AEs, clinical laboratory test results, vital signs
    measurements, SpO2, ECGs, and assessments of somnolence (UMSS).
    E.5.2Secondary end point(s)
    Efficacy Variables: Pain intensity will be assessed by scale type dependent on whether the patient is postoperative or intubated and the patient’s age.
    Pain assessments will be performed prior to each administration of IV buprenorphine and/or supplemental pain medication. The nurse will be instructed to record the pain score or have the patient self-report using 1 of the following scales: Comfort "behavior" Scale, FLACC, or FPS-R.

    Pharmacokinetic Analysis:

    Plasma buprenorphine concentrations, sampling times, dosing data, and individual-specific covariate effects, including age and weight, will be collected.
    Compartmental PK parameters will be estimated using standard population nonlinear mixed effects methodology. Parameters of primary interest include clearance (CL/F) and apparent central volume of distribution (Vc/F). Point estimates and some measure of parameter estimation precision will be obtained for all population model parameters. The population PK analysis will be reported in a separate report from the clinical study report.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Efficacy Analysis:
    Descriptive statistics (n, mean, standard error, median, minimum, and maximum) will be tabulated for pain Intensity (Comfort "behavior" Scale, FLACC, FPS-R) at specified time intervals within each age group.
    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 No
    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) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    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 No
    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 No
    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.8.3 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 EEA29
    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
    Argentina
    Australia
    Austria
    Brazil
    Canada
    Chile
    Hungary
    India
    Italy
    Slovakia
    Spain
    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
    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 months
    E.8.9.1In the Member State concerned days18
    E.8.9.2In all countries concerned by the trial days18
    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: 60
    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: 10
    F.1.1.4Infants and toddlers (28 days-23 months) Yes
    F.1.1.4.1Number of subjects for this age range: 24
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 26
    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
    Written informed consent for the study will be obtained from all patients' parents/legal guardians.
    Assent by the patient will be documented in accordance with the policies of the investigator's IRB/EC and local regulations
    F.3.3.7Others Yes
    F.3.3.7.1Details of other specific vulnerable populations
    Peadiatric patients aged from birth to 6 years of age
    F.4 Planned number of subjects to be included
    F.4.1In the member state12
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 35
    F.4.2.2In the whole clinical trial 60
    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)
    As detailed in study protocol (section 9.5.5/9.5.6).
    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 Decision2011-10-17
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2011-10-10
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
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