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    The EU Clinical Trials Register currently displays   43861   clinical trials with a EudraCT protocol, of which   7284   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:2016-004473-41
    Sponsor's Protocol Code Number:2016RC22
    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:2017-09-11
    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 ConcernedUK - MHRA
    A.2EudraCT number2016-004473-41
    A.3Full title of the trial
    INvestigating COPD Outcomes, Genomics and Neutrophilic Inflammation with Tiotropium and Olodaterol (INCOGNITO trial)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Investigating whether two different COPD inhalers have different effects on chest infections
    A.3.2Name or abbreviated title of the trial where available
    INCOGNITO trial- Investigating COPD lung infections with two different
    A.4.1Sponsor's protocol code number2016RC22
    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 SponsorUniversity of Dundee and NHS Tayside
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportBoehringer-Ingelheim
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationUniversiyt of Dundee
    B.5.2Functional name of contact pointChalmers
    B.5.3 Address:
    B.5.3.1Street AddressDivision of Cardiovascular & Diabetes Medicine
    B.5.3.2Town/ cityLevel 5, Mailbox 12
    B.5.3.3Post codeDD1 9SY
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number01382 383642
    B.5.6E-mailj.chalmers@dundee.ac.uk
    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 Spiolto Respimat
    D.2.1.1.2Name of the Marketing Authorisation holderBoehringer Ingelheim
    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 nameSpiolto Respimat
    D.3.4Pharmaceutical form Inhalation solution
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPInhalation use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTiotropium bromide
    D.3.9.1CAS number 186691-13-4
    D.3.9.4EV Substance CodeAS2
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2.5
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNOlodaterol
    D.3.9.1CAS number 868049-49-4
    D.3.9.4EV Substance CodeAS3
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2.5
    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 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 Relvar Ellipta
    D.2.1.1.2Name of the Marketing Authorisation holderGlaxosmithkline
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 nameRelvar Ellipta
    D.3.4Pharmaceutical form Inhalation powder
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPInhalation use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNFluticasone furoate
    D.3.9.1CAS number 397864-44-7
    D.3.9.4EV Substance CodeAS4
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number92
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNVilanterol
    D.3.9.1CAS number 503068-34-6
    D.3.9.4EV Substance CodeAS5
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number22
    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.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Chronic obstructive pulmonary disease
    E.1.1.1Medical condition in easily understood language
    COPD- smoking related lung disease
    E.1.1.2Therapeutic area Diseases [C] - Respiratory Tract Diseases [C08]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10010952
    E.1.2Term COPD
    E.1.2System Organ Class 100000015472
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To determine the effects of the Tiotropium and olodaterol combination (Spiolto respimat 2.5/2.5ug) 2 puffs once daily vs Relvar Ellipta (fluticasone furoate 92 micrograms, vilaterol 22 micrograms) 1 puff once daily on airway bacterial load (the numbers of bacteria found) from induced sputum
    E.2.2Secondary objectives of the trial
    To determine the effects of the Tiotropium and olodaterol combination (Spiolto respimat 2.52.5ug) 2 puffs once daily vs Relvar Ellipta (fluticasone furoate 92 micrograms, vilaterol 22 micrograms) 1 puff once daily on the airway microbiota (a technology that is very sensitive to detect bacteria). Microbiota will be characterised in sputum, oropharyngeal swabs and nasopharyngeal swabs

    To determine the effects of the Tiotropium and olodaterol combination (Spiolto respimat 2.52.5ug) 2 puffs once daily vs Relvar Ellipta (fluticasone furoate 92 micrograms, vilaterol 22 micrograms) 1 puff once daily on lung inflammation caused by neutrophils using several different sputum tests

    To evaluate the safety and tolerability of Tiotropium and olodaterol combination (Spiolto respimat 2.52.5ug) 2 puffs once daily vs Relvar Ellipta (fluticasone furoate 92 micrograms, vilaterol 22 micrograms) 1 puff once daily in patients previously treated with inhaled corticosteroids

    To evaluate patient reported out
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    • Male and female patients aged > 40 years
    • Current or ex smokers having at least a 10 pack year smoking history
    • A clinical diagnosis of COPD made by a physician
    • Post-bronchodilator FEV1/FVC ratio at screening of <70%
    • Moderate to Very Severe COPD (GOLD II-IV) according to consensus guidelines consisting of a post-bronchodilator FEV1 <80% predicted at screening.
    • Currently treated with inhaled corticosteroids (with or without long acting bronchodilators) for at least 12 months prior to screening.
    • Able to perform all study procedures including spirometry and questionnaires with minimal assistance
    • Blood eosinophil count less than 300 eosinophil cells per microlitre on bloods taken at screening.
    • Able to produce a sputum sample at the baseline visit (nebulised sputum induction is acceptable)
    E.4Principal exclusion criteria
    • Inability to give informed consent
    • Asthma
    • Acute Antibiotics within 28 days prior to screening
    • Current use of the following: roflumilast, ritonavir, itraconazole, telithromycin, or ketoconazole (or other strong CYP3A4 inhibitors).
    • Systemic Immunosuppressive medication including current oral corticosteroids at a dose >5mg for >28 days.
    • Glomerular filtration rate (eGFR) below 30ml/min/1.73m2 or requiring dialysis. This will be determined at screening.
    • Use of any investigational drugs within five times of the elimination half-life after the last study dose or within 30 days, whichever is longer.
    • Known allergy, intolerance or contraindication to any of the study drugs
    • Unstable co-morbidities (cardiovascular disease, active malignancy) which in the opinion of the investigator would make the patient unsuitable to be enrolled in the study
    • An exacerbation of COPD occurring during the 28 days prior to screening requiring treatment with either oral corticosteroids and antibiotics.
    • An exacerbation requiring treatment with antibiotics or corticosteroids between the screening and randomization visit
    • Pregnancy or breast feeding
    • Women of child bearing potential (WOCBP) who are not practicing an acceptable method of contraception (see below)
    • Long term oxygen therapy
    • Lapp lactase deficiency, glucose-galactose malabsorption or another inherited disorder of galactose metabolism.
    Acceptable forms of contraception:
    • 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
    • vasectomised partner
    • sexual abstinence
    E.5 End points
    E.5.1Primary end point(s)
    Bacterial load of total respiratory pathogens determined by quantitative polymerase chain reaction. Continuous variable at 0, 1, 2, 3 and 6 months
    E.5.1.1Timepoint(s) of evaluation of this end point
    Continuous variable at 0, 1, 2, 3 and 6 months
    E.5.2Secondary end point(s)
    1) Bacterial community composition determined by 16S microbiome sequencing as measured by the Shannon Diversity index. Additional outcome will be relative abundance of Haemophilus OTUs at genus level or relative abundance of proteobacteria at phylum level. Proportion of patients with dysbiosis as defined by >40% relative OTU’s of a single organism.

    2) Sputum neutrophil elastase activity determined using an activity based immunoassay

    3) Sputum neutrophil extracellular traps determined using a validated ELISA

    4) Sputum cytokines (CXCL-8, IL17, IL-1beta, resistin, IL13)

    5) Ex-vivo phagocytosis of Haemophilus tested by incubating sputum cells with FITC-labelled H. influenzae*

    6) Frequency of adverse events and serious adverse events between groups

    7) Quality of life using St. George’s Respiratory Questionnaire(SGRQ, COPD assessment test (CAT), MRC dyspnoea score and transitional dyspnoea index

    8) Comparison of time to first exacerbation of COPD, Number of exacerbations
    Changes in FEV1 measurement

    E.5.2.1Timepoint(s) of evaluation of this end point
    Continuous variables will be evaluated using regression analysis incorporating data from all available time points (0 to 6 months) while events at fixed time points e.g tiem to first exacerbation or frequency of exacerbations over 6 months will be evaluated at the end of the follow-up period (6 months)
    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) No
    E.7.4Therapeutic use (Phase IV) Yes
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    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 No
    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 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
    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 months11
    E.8.9.1In the Member State concerned days29
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months6
    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: 20
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 100
    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 state120
    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)
    Following the end of study, patients will be continued, started or restarted on the appropriate treatment for their COPD.
    All of the investigational drugs used in this study are commonly used treatments for patients with COPD and can therefore be offered to patients following the study if determined to be appropriate by the local investigator with discussion with the patient's GP and/or usual respiratory physician.
    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 Decision2017-03-21
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-02-09
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2019-11-26
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