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The European Union Clinical Trials Register   allows you to search for protocol and results information on:
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    The EU Clinical Trials Register currently displays   43925   clinical trials with a EudraCT protocol, of which   7306   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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    EudraCT Number:2014-003581-25
    Sponsor's Protocol Code Number:APA-III
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2014-12-15
    Trial results View results
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    A. Protocol Information
    A.1Member State ConcernedGermany - BfArM
    A.2EudraCT number2014-003581-25
    A.3Full title of the trial
    Anti-inflammatory pulmonal therapy of CF-patients with Amitriptyline and Placebo - Randomised, double-blind, placebo-controlled cohort trial
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Therapy of lungs of CF-patients with Amitriptyline - a randomised, double-blind, placebo-controlled cohort trial
    Anti-inflammatorische pulmonale Therapie von CF-Patienten mittels Amitriptylin und Placebo - Placebokontrollierte, prospektive, randomisierte, doppel-blinde Kohorten-Studie
    A.4.1Sponsor's protocol code numberAPA-III
    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 Hospital Tuebingen
    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 supportBMBF
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationUniversity Children's Hospital, CPCS
    B.5.2Functional name of contact pointDr.med. Andreas Hector
    B.5.3 Address:
    B.5.3.1Street AddressHoppe-Seyler-Str. 1
    B.5.3.2Town/ cityTuebingen
    B.5.3.3Post code72076
    B.5.4Telephone number+4970712981341
    B.5.5Fax number+4907071294450
    D. IMP Identification
    D.IMP: 1
    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. name Amitriptylin-CT
    D. of the Marketing Authorisation holderCT-Arzneimittel GmbH Berlin
    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 nameAmitriptyline
    D.3.4Pharmaceutical form Capsule
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    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. cell therapy medicinal product No
    D. therapy medical product No
    D. Engineered Product No
    D. ATIMP (i.e. one involving a medical device) No
    D. 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 placeboCapsule, hard
    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
    Amitriptyline reduces ceramide concentrations in bronchial epithelial cells and reduces cell death and reduces the deposition of DNA on the respiratory epithelium. This reduction promotes the elimination of P. aeruginosa bacteria from the lung. As a result, treatment normalizes inflammation in CF lungs. Amitriptyline thus reduces systemic and local inflammation. Because of these effects, amitriptyline increases lung function in CF patients.
    E.1.1.1Medical condition in easily understood language
    Amitriptyline reduces cell death in epithelial cells of the lung, reduces inflammation and increases lung function.
    E.1.1.2Therapeutic area Diseases [C] - Respiratory Tract Diseases [C08]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Difference in absolute FEV1 % predicted between verum and placebo at week 8 compared to baseline
    E.2.2Secondary objectives of the trial
    1. Maintenance of the reached FEV1 in the verum group between week 8 and week 16.
    2. Absolute and relative FEV1 as % predicted after 4, 8, 12 and 16 weeks compared to baseline, if not primary;
    3. All other lung function parameters (FVC, MEFs and lung clearance index-LCI);
    4. Concentration of Ceramide in sputum;
    5. Concentration of pro-inflammatory cytokines, change of anti-inflammatory IL-10 in tracheal mucus;
    6. Content of DNA and granulocyte concentration in sputum;
    7. Bacterial colonisation in sputum;
    8. Number of exacerbations of pulmonary symptoms;
    9. Incidence of discontinuation of treatment because perceived side ef-fects.
    10. Changes in body weight
    11. Quality of life questionnaire adapted to CF
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Cystic Fibrosis is verified;
    2. Patient is older than 12 years;
    3. Patients weight is more than 35 kg;
    4. FEV1 is higher than 25% and lower than 100% (two times in 3 months);
    5. The patients lung is colonised with bacteria;
    6. No acute pulmonal illness is present;
    7. Lung function testing is possible;
    8. A full course of therapy is possible without any restrictions;
    9. Informed consent is given.
    E.4Principal exclusion criteria
    1. FEV1 in screening and baseline differs more than 10%;
    2. Clinicial detoriation is present (exacerbation symptoms);
    3. Change of CRP of more than 50% in screening period;
    4. Glaucoma, seizures, heart insufficiency or major depression is pre-sent;
    5. Intravenous antibiotic treatment was necessary for the last 2 weeks prior to the trial;
    6. High dose steroid therapy;
    7. On-therapy of tobramycine in the last 2 weeks;
    8. Involvement of the patient in another study;
    9. Pregnancy.
    E.5 End points
    E.5.1Primary end point(s)
    Difference in mean absolute differences in percent predicted FEV1 between verum and placebo at week 8 compared to baseline
    E.5.1.1Timepoint(s) of evaluation of this end point
    at week 8 compared to baseline
    E.5.2Secondary end point(s)
    - Maintenance of the reached FEV1 amount in the verum group between week 8 and week 16 re-garding a difference up to 4,2% as being equivalent.
    - Absolute and relative FEV1 increase after 4, 8, 12 and 16 weeks compared to baseline, if not pri-mary.
    - All other lung function parameters (FVC, MEF25, MEF50, MEF75, MEF25-75, LCI) after 4, 8, 12 and 16 weeks compared to baseline.
    - Concentration of Ceramide in sputum after 8 and 16 weeks compared to baseline.
    - Concentration of pro-inflammatory cytokines (IL-6, IL-8, TNF╬▒), change of anti-inflammatory IL-10 in tracheal mucus after 4, 8, 12 and 16 weeks compared to baseline.
    - Content of DNA and granulocyte concentration in sputum after 4, 8, 12 and 16 weeks compared to baseline.
    - Chronic bacterial colonisation (cumulative Cfu) in sputum after 4, 8, 12 and 16 weeks compared to baseline.
    - Number of exacerbations of pulmonary symptoms (pulmonary infections treated with antibiotics) after 8 and 16 weeks compared to baseline.
    - Incidence of discontinuation of treatment due to perceived side effects.
    - Question 18 of quality of life questionnaire adapted to CF after 8 and 16 weeks compared to baseline.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Each after 4, 8, 12 and 16 weeks compared to baseline.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis Yes
    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 Yes
    E.6.10Pharmacogenetic Yes
    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. 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 concerned5
    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 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
    There is a follow up visit 28 days after therapy will be finished because of safety reasons
    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 days
    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: 15
    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) Yes
    F. of subjects for this age range: 15
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 87
    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 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 state102
    F.4.2 For a multinational trial
    F.4.2.2In the whole clinical trial 102
    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)
    Patients are in routine observation (as outpatients) done all three months. After follow up visit, all patients will be routinely treated by sites and investigators.
    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 Decision2015-03-17
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-05-26
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2019-09-30
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