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    Summary
    EudraCT Number:2018-001630-18
    Sponsor's Protocol Code Number:CWL15001
    National Competent Authority:Bulgarian Drug Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Trial now transitioned
    Date on which this record was first entered in the EudraCT database:2023-03-02
    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 ConcernedBulgarian Drug Agency
    A.2EudraCT number2018-001630-18
    A.3Full title of the trial
    A randomized, parallel group, multi-center study of a fentanyl nasal spray compared with placebo nasal spray for postoperative pain management and prolonged open treatment over up to 120 hours postoperatively compared with intravenous patient-controlled analgesia using morphine
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Fentanyl nasal spray as a pain reliever after orthopedic surgery
    A.3.2Name or abbreviated title of the trial where available
    Parallel group, multi-center study of Fentanyl Nasal Spray in patients with postoperative pain
    A.4.1Sponsor's protocol code numberCWL15001
    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 Sponsor5med 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 support5med GmbH
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation5med GmbH
    B.5.2Functional name of contact pointDr. Stefan Nardi-Hiebl
    B.5.3 Address:
    B.5.3.1Street AddressLena-Christ-Strasse 2
    B.5.3.2Town/ cityGruenwald
    B.5.3.3Post code82031
    B.5.3.4CountryGermany
    B.5.4Telephone number+4994059498733
    B.5.6E-mailstefan.nardi-hiebl@5med.eu
    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 nameFentanyl Nasal Spray
    D.3.2Product code Test
    D.3.4Pharmaceutical form Nasal spray, solution
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPNasal use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNfentanyl citrate
    D.3.9.1CAS number 990-73-8
    D.3.9.2Current sponsor codeTest
    D.3.9.3Other descriptive nameFentanyl citrate
    D.3.9.4EV Substance CodeSUB02129MIG
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    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 Yes
    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 RoleComparator
    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 Morphin-hameln 100 mg Injektionslösung
    D.2.1.1.2Name of the Marketing Authorisation holderhameln pharma gmbh
    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 nameMorphin-hameln 100 mg Injektionslösung
    D.3.2Product code Comparator
    D.3.4Pharmaceutical form Injection/infusion
    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.3.8INN - Proposed INNmorphine sulfate
    D.3.9.1CAS number 6211-15-0
    D.3.9.2Current sponsor codeReference
    D.3.9.3Other descriptive nameMorphine sulfate
    D.3.9.4EV Substance CodeSUB14597MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    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 placeboNasal spray, solution
    D.8.4Route of administration of the placeboNasal use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Management of pain following orthopedic surgery
    E.1.1.1Medical condition in easily understood language
    Pain after orthopedic surgery
    E.1.1.2Therapeutic area Diseases [C] - Symptoms and general pathology [C23]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10036236
    E.1.2Term Postoperative pain relief
    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
    The primary objective of the present trial is the assessment of the efficacy of Fentanyl Nasal Spray in combination with an applicator as compared to placebo for the management of postoperative pain. Pain caused by orthopedic surgery will serve as a model for postoperative pain. Evidence from the literature will be used to bridge analgesic effectiveness of nasal fentanyl from pain primarily caused by activation of nociceptors to visceral pain (e.g. caused by abdominal surgery).
    E.2.2Secondary objectives of the trial
    The secondary objective of the present trial is the assessment of the tolerability and side-effects of prolonged postoperative administration of Fentanyl Nasal Spray as compared with Standard of Care [morphine, applied by standard of care treatment via i.v. PCA (patient-controlled analgesia)]. Furthermore, the usability of the administration control device will be assessed.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    [1] Male or female patients ≥18 years of age
    [2] Intended stay in a Post Anesthesia Care Unit (PACU) or recovery room unit for at least 120 minutes after orthopedic surgery performed using general anesthesia for one of the following procedures:
    - knee joint endoprosthesis surgery
    - isolated fracture of the femur, tibia, fibula, or calcaneus, treated by open reduction and internal fixation (ORIF)
    [3] American Society of Anesthesiology (ASA) physical status I, II, or III
    [4] Patients who are expected to develop acute moderate or severe pain expected to require parenteral opioids for at least 24 hours after surgery
    [5] Patients capable of handling the administration control device
    [6] Patients willing and able (e.g. mental and physical condition) to participate in all aspects of the study as evidenced by providing signed written informed consent.
    E.4Principal exclusion criteria
    [1] History of hypersensitivity or intolerance to the active substance or any of the excipients of the study medication
    [2] Patients with respiratory depression, i.e. less than 10 breaths per minute
    [3] Patients with clinically significant obstructive airways disease, which is still symptomatic under stable treatment
    [4] Patients scheduled for post-operative analgesia supplied by a single-shot or continuous regional technique
    [5] Patients scheduled to receive non-steroidal anti-inflammatory drugs (NSAIDs) within 12 hours before surgery, immediately after operation, and during the first 24 hours after start of treatment with study medication
    [6] Patients scheduled to received local anesthetics in the surgical area
    [7] Patients expected to require another surgical procedure within 48 hours post-operatively
    [8] Patients who are expected to receive opioids other than fentanyl or sufentanil intra-operatively or fentanyl postoperatively
    [9] Known or suspected opioid tolerance or history of opioid dependence
    [10] Chronic treatment with opioids preoperatively on a fixed scheduled (regular) basis within 7 days before surgery
    [11] Chronic medication with gabapentine or pregabaline
    [12] Patients treated with medication that contains sodium oxybate
    [13] Patients with repeated episodes of epistaxis
    [14] Previous radiation therapy in the face area
    [15] Intake of MAO inhibitors within the last 14 days prior to randomization
    [16] Current anatomical abnormalities of the nose that is likely to interfere with the mucosal absorption of fentanyl via the nasal cavities
    [17] Severe common cold, intensive hay fever or any other circumstances requiring the use of congestive nasal sprays during the study period
    [18] Patient is currently enrolled in, or has completed less than 30 days before the screening examination of the present trial another clinical trial with an investigational drug
    [19] Previous enrolment in this study
    [20] Pregnant or breast-feeding women
    [21] Women of childbearing potential unable or unwilling to use highly effective contraceptive measures until start of hospitalization. Reliable methods for women are:
    - combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal);
    - progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable);
    - intrauterine device (IUD);
    - intrauterine hormone-releasing system (IUS);
    - bilateral tubal occlusion;
    - vasectomized partner;
    - sexual abstinence.
    [22] Legal incapacity and/or other circumstances rendering the patient unable to understand the nature, scope and possible consequences of the study
    [23] Alcohol/drug dependence or abuse (excluding tobacco abuse)
    [24] Unreliability or lack of cooperation
    [25] Any other condition of the patient (e.g., serious or unstable medical or psychological condition, acute psychosis) that in the opinion of the investigator may compromise evaluation of the study treatment or may jeopardize patient’s safety, compliance or adherence to protocol requirements.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint in the present trial is:
    Survival distribution in the period from start of treatment with the first dose of the study medication until terminating the trial due to inadequate analgesia as required by the patient or felt necessary by the investigator within the first 24 hours after start of treatment with non-terminating patients censored at 24 hours.
    E.5.1.1Timepoint(s) of evaluation of this end point
    After the end of the clinical part of the trial.
    E.5.2Secondary end point(s)
    Secondary endpoints are:
    • sum of ratings of pain intensity on a 11-point numeric rating scale at pre-defined points in time: at hours 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24 after start of treatment (TotPaR)
    • sum of pain intensity difference ratings on a 11-point numeric rating scale comparing the pain rating before start of treatment (0) and ratings at pre-defined points in time (SPID): at hours 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, and 120 after start of treatment (Patients will not be woken up for a postoperative measurement. The last observation carried forward method will be used to replace a missing value
    • percentage of patients who terminate the study due to inadequate analgesia during the 24-hours treatment period
    • percentage of patients who terminate the study due to any reason during the 24-hours treatment period
    • number of actuations administered
    • number of unsuccessful actuations during lock-out period
    • patient's rating of usability [System Usability Scale (SUS)]
    • patient’s global rating of efficacy using a four-point Likert scale (poor, fair, good, or excellent)
    • investigator's global rating of efficacy (Likert scale: see above)
    • evaluation of ease of care (patients, nursing staff, and physiotherapists).
    E.5.2.1Timepoint(s) of evaluation of this end point
    After the end of the clinical part of the trial.
    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 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) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    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) Yes
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial3
    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 concerned11
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA12
    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
    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 years0
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years0
    E.8.9.2In all countries concerned by the trial months6
    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 No
    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) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 80
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 80
    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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2023-03-02. Yes
    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 No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state100
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 160
    F.4.2.2In the whole clinical trial 160
    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)
    After the subject has ended the participation in the trial he/she can continue with a standard analgesic treatment for relief of pain.
    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 Decision2023-07-11
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2023-07-19
    P. End of Trial
    P.End of Trial StatusTrial now transitioned
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