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    The EU Clinical Trials Register currently displays   43851   clinical trials with a EudraCT protocol, of which   7283   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:2015-001952-31
    Sponsor's Protocol Code Number:CRS-03
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2015-11-27
    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 ConcernedGermany - BfArM
    A.2EudraCT number2015-001952-31
    A.3Full title of the trial
    A multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial to assess efficacy and safety of the herbal medicinal product Sinupret extract coated tablets in patients with chronic rhinosinusitis
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial to assess efficacy and safety of the herbal medicinal product Sinupret extract coated tablets in patients with chronic rhinosinusitis
    Eine multizentrische, randomisierte, doppelt verblindete, placebo-kontrollierte Parallelgruppenstudie zur Beurteilung der Wirksamkeit und Sicherheit des pflanzlichen Arzneimittels Sinupret Extract überzogene Tabletten für die Behandlung chronischer Rhinosinusitis
    A.3.2Name or abbreviated title of the trial where available
    Sinupret extract coated tablets in chronic rhinosinusitis
    A.4.1Sponsor's protocol code numberCRS-03
    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 SponsorBionorica SE
    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 supportBionorica SE
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationBionorica SE
    B.5.2Functional name of contact pointClinical Research International Dep
    B.5.3 Address:
    B.5.3.1Street AddressKerschensteinerstr. 11-15
    B.5.3.2Town/ cityNeumarkt
    B.5.3.3Post code92318
    B.5.3.4CountryGermany
    B.5.5Fax number0049091812316894
    B.5.6E-mailcrs-03@bionorica.de
    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 Sinupret extract
    D.2.1.1.2Name of the Marketing Authorisation holderBionorica SE
    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 nameSinupret extract coated tablets
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.3Other descriptive nameDRY EXTRACT (3-6:1) OF GENTIAN ROOT, PRIMULA FLOWERS, SORREL HERB, ELDER FLOWERS, VERVAINE HERB (1:3:3:3:3), EXTRACTING AGENT: ETHANOL 51% (M/M)
    D.3.9.4EV Substance CodeSUB170604
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number160
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    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 Yes
    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 placeboTablet
    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 rhinosinusitis
    Chronische Rhinosinusitis
    E.1.1.1Medical condition in easily understood language
    Chronic inflammation of the sinuses
    Chronische Nebenhöhlenentzündung
    E.1.1.2Therapeutic area Diseases [C] - Ear, nose and throat diseases [C09]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.1
    E.1.2Level LLT
    E.1.2Classification code 10052106
    E.1.2Term Rhinosinusitis
    E.1.2System Organ Class 100000004862
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To assess the efficacy of the herbal medicinal product Sinupret extract versus placebo in the treatment of chronic rhinosinusitis (CRS) in adults.
    E.2.2Secondary objectives of the trial
    • To assess safety and tolerability of Sinupret extract versus placebo during the 16-week treatment phase and the 4-week follow-up phase.
    • To assess the effect of Sinupret extract versus placebo on selected inflammatory parameters in nasal secretions after 8- and 16-week treatment periods compared to baseline in a subset of approximately 60 patients.
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Analysis of inflammatory parameters in nasal secretions
    Untersuchung von Entzündungsparametern im Nasensekret
    E.3Principal inclusion criteria
    1. Signed informed consent (IC) including data protection declaration
    2. Male and female outpatients aged ≥18 and ≤75 years Women will be considered for inclusion if they are not pregnant (as confirmed by urine pregnancy test at V1 and V2), not breastfeeding, or if they are surgically sterile (have had a documented bilateral oophorectomy and/or hysterectomy) or if menopause is ensured (at least 12 months without menstrual bleeding). Women of childbearing potential must use a highly effective (failure rate less than 1% per year, i.e. Pearl Index <1) method of contraception 2 weeks prior to trial inclusion and during the screening/treatment period of the clinical trial (e.g. vasectomized partner, sexual abstinence - the lifestyle of the female has to be such that there is complete abstinence from intercourse from 2 weeks prior to the first dose of trial medication until at least 72 hours after treatment - implants, injectables, combined oral contraceptives, or hormonal intrauterine devices).
    3. Diagnosis of bilateral CRS without nasal polyps confirmed by:
    • Nasal endoscopy during the screening phase to confirm inflammation, mucopurulent discharge, and/or edema/mucosal obstruction primarily in middle meatus without nasal polyps being present
    • At the discretion of the investigator, results from a historic imaging diagnostic, i.e. computer tomography (CT), digital volume tomography (DVT), or magnetic resonance tomography (MRT) (before screening and not older than 24 months, not taken during acute exacerbation), which will be considered additionally for confirmation of bilateral involvement of middle meatus and paranasal sinuses without resolution of symptoms (mucosal changes within the ostiomeatal complex and/or sinuses)
    4. Bilateral CRS characterized by:
    • Presence of CRS symptoms for >52 weeks prior to enrolment (V1) as documented in the medical file of the patient
    • Major Symptom Score (MSS) ≥10 at V1 and V2 as assessed by the investigator (MSSINV), and rhinorrhea (anterior or posterior) and pain (facial pain or headache) each of at least moderate intensity (score ≥2)
    E.4Principal exclusion criteria
    1. Sinus surgery within the last 2 years (solitary sinus puncture is allowed)
    2. Inferior turbinate reduction (by surgery or other methods) within the last 3 months
    3. Presence or history of uni- or bilateral nasal polyps
    4. Moderate to severe co-morbid asthma, including allergic asthma
    5. Cystic fibrosis
    6. Perennial (e.g. patients with clinical symptoms of allergic rhinitis against house dust/mite antigen) or seasonal allergic rhinitis
    7. Rhinitis medicamentosa (drug induced rhinitis)
    8. Aspirin-exacerbated respiratory disease (aspirin sensitivity)
    9. Dentogenic sinusitis or otherwise unilateral sinusitis
    10. Presence of anatomical deviations of the nasal septum that significantly impair nasal and paranasal ventilation/airflow
    11. Known hypersensitivity to trial medication or excipients
    12. Rare hereditary problems of fructose intolerance, galactose intolerance, lactase deficiency, glucose-galactose malabsorption, or sucrase-isomaltase insufficiency
    13. Signs or symptoms of acute bacterial sinusitis (e.g. fever >38.5°C, orbital complications, severe unilateral frontal headache, or toothache)
    14. Treatment with antihistamines within 4 weeks prior to V1
    15. Treatment with 2-3.5% hypertonic saline solution within 2 weeks prior to V1
    16. Treatment with systemic or nasal antibiotics or corticosteroids within 4 weeks prior to V1
    17. Treatment with decongestant preparations (α-sympathomimetics), analgesics (including systemic non-steroidal inflammatory drugs [NSAIDs], including paracetamol), mucolytics/secretolytics, or alternative medicine preparations for treatment of common cold-like symptoms or with immunomodulating properties within 7 days prior to V1
    18. Peptic ulcer
    19. Gastritis
    20. Other diseases within 5 years prior to V1 that, in the opinion of the investigator, disqualifies the patient for trial enrolment (e.g. liver or kidney disease, severe somatopathic, neurological and/or psychiatric diseases, history of malignancy, alcohol or drug abuse, or immunodeficiency)
    21. Parallel participation in another clinical trial, participation in a different trial within less than 6 weeks prior to trial entry, or previous randomization into this clinical trial
    22. Known to be, or suspected of being unable to comply with the clinical trial protocol (CTP) that in the opinion of the investigator disqualifies the patient for trial enrolment (e.g. no permanent address, known to be non-compliant, or presenting an unstable psychiatric history)
    23. Legal incapacity and/or other circumstances rendering the patient unable to understand the nature, scope, and possible impact of the clinical trial
    24. Patients in custody by juridical or official order
    25. Patients who have difficulties in understanding the local language in which the patient information (PI) is given
    26. Patients who are members of the staff of the investigational site, staff of the sponsor or involved CRO, the investigator him/herself or close relatives
    E.5 End points
    E.5.1Primary end point(s)
    The primary efficacy endpoint
    of this trial is MSSINV at V7.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Visit 7 (week 16).
    E.5.2Secondary end point(s)
    1. MSSINV at V4, V5, and V6
    2. Major symptom score as assessed by the patient (MSSPAT) at V4, V5, V6, and V7
    3. Minimal MSSINV of all visits from V4 to V7
    4. Minimal MSSPAT of all visits from V4 to V7
    5. Investigator’s ratings of each individual CRS symptom (i.e. rhinorrhea [anterior], rhinorrhea [posterior], nasal congestion, headache, and facial pain/pressure) at V4, V5, V6, and V7
    6. Patient’s ratings of each individual CRS symptom (i.e. rhinorrhea [anterior], rhinorrhea [posterior], nasal congestion, headache, and facial pain/pressure) at V4, V5, V6, and V7
    7. 22-Item Sino-Nasal Outcome Test total score (SNOT-22Total Score) as well as SNOT-22 primary nasal score (SNOT-22 PNS) and SNOT-22 general quality of life score (SNOT-22ALQ) at V4, V5, V6, and V7
    8. Total symptom severity assessed by the patient on a visual analogue scale (VAS) at V4, V5, V6, and V7
    9. Proportion of patients whose MSSINV and MSSPAT improved by ≥30%, ≥40%, ≥50%, ≥60% and ≥70% at V4, V5, V6, and V7. Responders are defined as patients who show at least an MSS improvement of ≥30%
    10. Patients with permitted concomitant drug and non-drug therapy (i.e. isotonic saline solution as nasal spray, nasal irrigation [nasal lavage], or ultrasonic nebulizer) for CRS
    11. Patients with premature termination due to exacerbation of CRS symptoms
    12. Investigator’s and patient’s overall assessment of efficacy at V4, V5, V6, and V7
    13. Absolute concentrations of selected inflammatory parameters (e.g. myeloperoxidase [MPO], eosinophil cationic protein [ECP], cytokines, α2-macroglobulin, HMGB-1, albumin) in nasal secretions collected at V2, V5 and V7 for a subset of approximately 60 patients in approximately 10 investigational sites in Germany
    14. Change from baseline (V2) in the concentration of selected inflammatory parameters (e.g. MPO, ECP, cytokines, α2-macroglobulin, HMGB-1, albumin) in nasal secretions at V5 and V7 for a subset of approximately 60 patients in approximately 10 investigational sites in Germany
    15. Pharmacoeconomic evaluation (utilization of health care resources) including:
    • Unscheduled or unforeseen visits to any physician due to CRS-related symptoms
    • CRS-related absenteeism from work (or other daily activities)
    • Patient’s Work Productivity and Activity Impairment, General Health (WPAI:GH) ratings at V4, V5, V6, and V7. The following validated endpoints will be analyzed: percentage of work time missed due to health, percentage of impairment while working due to health, percentage of overall work impairment due to health, and percentage of activity impairment due to health
    E.5.2.1Timepoint(s) of evaluation of this end point
    Visit 2 (baseline), visit 4 (week 4), visit 5 (week 8), visit 6 (week 12), visit 7 (week 16).
    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 Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic Yes
    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) 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 concerned21
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA52
    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
    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 months2
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months2
    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: 437
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 77
    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 No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state257
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 514
    F.4.2.2In the whole clinical trial 514
    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 completion of the clinical trial, participants will continue to be looked after by their doctors. The Investigators will discuss the best treatment options with the patient.
    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 Decision2016-03-08
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-04-14
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2017-08-23
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