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    The EU Clinical Trials Register currently displays   43865   clinical trials with a EudraCT protocol, of which   7286   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:2012-002996-32
    Sponsor's Protocol Code Number:12UK/DCsc04
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2012-10-10
    Trial results Removed from public view
    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 number2012-002996-32
    A.3Full title of the trial
    Preliminary evaluation of the efficacy and local tolerability of Injectable Diclofenac at 5, 12.5, 25 and 50 mg/mL, administered locally prior to surgery for the prevention of post-operative pain after third molar surgery
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Dental Pain 4
    A.3.2Name or abbreviated title of the trial where available
    Injectable Diclofenac for the prevention of post-operative dental pain
    A.4.1Sponsor's protocol code number12UK/DCsc04
    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 SponsorIBSA Institut Biochimique S.A.
    B.1.3.4CountrySwitzerland
    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 support
    B.4.2Country
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationIBSA Institut Biochimique S.A.
    B.5.2Functional name of contact pointBarbara Gugliotta
    B.5.3 Address:
    B.5.3.1Street AddressVia del Piano
    B.5.3.2Town/ cityP.O.Box 266, Pambio-Noranco
    B.5.3.3Post codeCH-6915
    B.5.3.4CountrySwitzerland
    B.5.4Telephone number0041583601000
    B.5.5Fax number0041583601655
    B.5.6E-mailbarbara.gugliotta@ibsa.ch
    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 nameDiclofenac HPBCD 25 mg/ml
    D.3.2Product code Diclofenac HPBCD 25 mg/ml
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMP
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNDiclofenac sodium
    D.3.9.1CAS number 15307-79-6
    D.3.9.4EV Substance CodeAS1
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    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.IMP: 2
    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 nameDiclofenac HPBCD 50 mg/ml
    D.3.2Product code Diclofenac HPBCD 50 mg/ml
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMP
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNDiclofenac sodium
    D.3.9.1CAS number 15307-79-6
    D.3.9.4EV Substance CodeAS3
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    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 placeboSolution for injection
    D.8.4Route of administration of the placeboOther use (Noncurrent)
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    post-surgical pain after lower third molar removal.
    E.1.1.1Medical condition in easily understood language
    post-surgical pain.
    E.1.1.2Therapeutic area Diseases [C] - Mouth and tooth diseases [C07]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 15.0
    E.1.2Level LLT
    E.1.2Classification code 10036286
    E.1.2Term Post-operative pain
    E.1.2System Organ Class 100000004863
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    This study will evaluate the analgesic efficacy and local tolerability of single doses of diclofenac sodium at four different strengths 5, 12.5, 25 and 50 mg/mL injected directly at the surgical area prior to oral surgery.
    E.2.2Secondary objectives of the trial
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Out-patients of either gender.
    2. Patients aged ≥ 18 to ≤ 65 years old.
    3. Subjects able and willing to give their written consent prior to inclusion in the study.
    4. Female subjects of childbearing potential must (1) have a negative urine pregnancy test at the inclusion visit, (2) be using an appropriate method of contraception according to the definition of Note of ICH M3 Guideline (implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or vasectomised partner), and (3) be willing to continue using the contraceptive method throughout the entire study period.
    5. Patients must (1) be able to comprehend the full nature and purpose of the study, including possible risks and side effects, (2) fully co-operate with the Investigator, (3) comply with the requirements of the entire study.
    6. Patients undergoing surgical extraction of a single, fully or partially impacted mandibular 3rd molar requiring bone removal.
    E.4Principal exclusion criteria
    1. Patients refusing to give Written Informed Consent.
    2. Patients not able to understand the purposes of the study or not willing to return for the control visits.
    3. Patients with major psychiatric disorders that, in the investigator’s opinion, could compromise study participation.
    4. Patients enrolled in any clinical trial in the previous 3 months.
    5. Employees of the study centre with direct involvement in the proposed study or other studies under the direction of the main investigator or study centre, as well as family members of the employees or investigator.
    6. Pregnant or breast-feeding women.
    7. Alcohol or drug abuse in the previous 12 months.
    8. Clinically significant or unstable concomitant disease whose sequelae might interfere with the study evaluation parameters.


    Trial specific

    9. Contralateral lower 3rd molar extraction or any other concomitant extraction.
    10. Surgery requiring general anaesthesia or sedation (including nitrous oxide by inhalation).
    11. Acute local or systemic infection occurring before surgery that in the investigator’s opinion, could confound the post-surgical evaluation.
    12. Patients with clinical signs or history of gastrointestinal disorders (e.g. gastritis, gastro-duodenal ulcer, gastrointestinal bleeding).
    13. Clinical signs or history of coagulation disorders.
    14. Patients with significant cardiac impairment (e.g. heart failure, ischemic heart disease), history of cerebrovascular disease (e.g. ictus), history of peripheral arterial disease or uncontrolled hypertension, (i.e. not stable = repeated measurements of systolic pressure > 160 mmHg or diastolic pressure > 95 mmHg, despite pharmacological treatment).
    15. Hepatic or renal impairment.
    16. Hypersensitivity to diclofenac or other NSAIDs.
    17. Patients under chronic treatment with topical or systemic analgesics/NSAIDs.
    18. Patients who have taken any medication as reported below:

    Non-Permitted Medications and wash-out period before surgery:
    Systemic NSAIDs or analgesics 24 hours
    Major or minor tranquilizers* 24 hours
    Muscle relaxers 24 hours
    Antihistaminesº 24 hours
    Long-acting NSAIDs 7 days
    Opioids 7 days
    MAO inhibitors 2 weeks
    Other antidepressants: SSRI, serotonin/norepinephrine reuptake inhibitors, and tricyclics 3 weeks
    Corticosteroids (any route of administration)2 months

    *Benzodiazepine-type anxiolytics with analgesic or muscle relaxant effect are allowed if their use had been started at least 6 months earlier for other medical reasons (their dose must be maintained unchanged during the study).
    ºUnless their use had been started at least 6 months earlier for other medical reasons (their dose must be maintained unchanged during the study).

    19. Patients under treatment with any medication that may interact with diclofenac: lithium, digoxin, diuretics, corticosteroids and other NSAIDs, anticoagulants and anti-platelet agents, antidiabetics, methotrexate, cyclosporine, quinolone antimicrobials, phenytoin.
    E.5 End points
    E.5.1Primary end point(s)
    The primary efficacy variable of the study will be the Area Under the Curve (AUC) of the pain scores over the time from end of surgery (time 0) to the 6 hour post-surgery. Pain will be scored by the patient on a 0-100 mm VAS (from 0 = no pain to 100 = worst pain imaginable).
    E.5.1.1Timepoint(s) of evaluation of this end point
    Pain assessed by the patient at the end of surgery (time 0) and at 15-minute intervals after surgery for a total of 6 hours.
    E.5.2Secondary end point(s)
    • Pain assessed by the patient at the end of surgery (time 0) and at 15-minute intervals after surgery for a total of 6 hours using a 100 mm VAS. After the in-clinic observation period, pain will be assessed hourly for an additional 6 hours and recorded in the patient diary. Pain will be also assessed at first rescue medication consumption.
    • Time to onset of pain. Starting time will be defined as the time at which surgery was completed to the first report of clinically meaningful pain (i.e. pain of 30 mm on the VAS scale).
    • Postsurgical extra-oral swelling will be also assessed measuring the distance between tragus and chin by the investigator immediately before administration of local anaesthesia, at 6h postoperatively before discharge, and at visits 2 and 3
    • Trismus (defined as distance between the left upper and lower incisors at maximal opening) will be measured by the investigator immediately before administration of local anaesthesia, at 6 hours postoperatively before discharge, and at visits 2 and 3.
    • Peak pain intensity will be the highest pain intensity observed during the 12 hours observation period.
    • Time to first use of rescue medication.
    • Amount of rescue medication (number of paracetamol tablets) used in each 15-minute time period.
    • Rescue medication consumption over the 24- and 48-hour intervals as described in the patient diary.
    • Patient and investigator global evaluation of the effectiveness of treatment, assessed after the 6 hour observation period and on Day 3 using a 5-point scale, where 4 = excellent; 3 = good; 2 = fair; 1 = poor; 0 = ineffective.

    Safety Variables:
    • Assessment of adverse events at any time during the study, particularly any local reaction(s) not commonly observed in the postsurgical period.
    • Assessment of wound healing by evaluating the severity of common (i.e. swelling, erythema, bruising) and uncommon (such as ulceration) intraoral signs using a 4-point scale, where 0=none, 1=mild, 2=moderate, 3=severe; at the end of the 6 hours observation period and at visit 2 and 3.
    • Assessment of recurrent bleeding as assessed by the investigator soon after surgery and every hour during the 6 hour observation period and categorised as 0 = no bleeding, 1 = slight ooze, 2 = persistent ooze, 3 = bleeding controlled with pressure or 4 = uncontrolled bleeding.
    • Vital signs (blood pressure, heart rate) measured at each visit.

    Exploratory Variable
    • C - Reactive Protein (CRP) concentrations will be measured immediately before surgery (Day 1), at 48 hours (Day 3) and after surgery on day 7.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Timepoints of evaluation of each secondary endpoint are described in the section above.
    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 No
    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) 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 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 Yes
    E.8.2.3Other No
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.4.1Number of sites anticipated in Member State concerned1
    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 No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee No
    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
    Completion of all trial procedures by participants (e.g last follow−up visit or questionnaire)
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years0
    E.8.9.1In the Member State concerned months5
    E.8.9.1In the Member State concerned days29
    E.8.9.2In all countries concerned by the trial years0
    E.8.9.2In all countries concerned by the trial months5
    E.8.9.2In all countries concerned by the trial days29
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1Number of subjects for this age range: 0
    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) No
    F.1.1.4.1Number of subjects for this age range: 0
    F.1.1.5Children (2-11years) No
    F.1.1.5.1Number of subjects for this age range: 0
    F.1.1.6Adolescents (12-17 years) No
    F.1.1.6.1Number of subjects for this age range: 0
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 75
    F.1.3Elderly (>=65 years) No
    F.1.3.1Number of subjects for this age range: 0
    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 No
    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 No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state75
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 75
    F.4.2.2In the whole clinical trial 75
    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)
    n/a
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2012-11-12
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-11-07
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2013-05-22
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