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    Summary
    EudraCT Number:2010-021349-36
    Sponsor's Protocol Code Number:VRP100419 (CHDR1018)
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2010-07-19
    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 ConcernedNetherlands - Competent Authority
    A.2EudraCT number2010-021349-36
    A.3Full title of the trial
    Randomised, Double-Blind, Placebo-Controlled Evaluation of the Safety and Duration of Action of 2 Single Inhaled Doses, 0.036 mg/kg (12X) and 0.072 mg/kg (24X), of RPL554, a Dual PDE 3/4 Inhibitor, in Allergic Asthmatics
    A.3.2Name or abbreviated title of the trial where available
    Evaluation of Nebulized RPL554 in asthmatics
    A.4.1Sponsor's protocol code numberVRP100419 (CHDR1018)
    A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorVerona Pharma plc
    B.1.3.4CountryUnited Kingdom
    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 organisation
    B.5.2Functional name of contact point
    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 nameRPL554
    D.3.2Product code RPL554
    D.3.4Pharmaceutical form Inhalation vapour, solution
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPInhalation 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) Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    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 Information not present in EudraCT
    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 placeboInhalation vapour, solution
    D.8.4Route of administration of the placeboInhalation use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Allergic Asthma
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 12.1
    E.1.2Level LLT
    E.1.2Classification code 10001705
    E.1.2Term Allergic asthma
    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 safety of nebulised RPL554 at 2 single inhaled doses of 0.036 mg/kg (12X) and 0.072 mg/kg (24X) in allergic asthmatics using standard safety measures with intensive monitoring of any potential cardiovascular effects.
    E.2.2Secondary objectives of the trial
    1) To investigate the onset, magnitude and duration of RPL554’s bronchodilator effects in terms of maximal increase from baseline (pre-bronchodilator) Forced Expiratory Volume in the first second (FEV1) and the duration of the bronchodilator response (in FEV1) over time.
    2) To investigate RPL554’s pharmacokinetics including the relationship between pharmacokinetics and bronchodilation; and the relationship between pharmacokinetics and any adverse events observed over time.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    •Males or females of non-child bearing potential: a) following hysterectomy or b) tubal ligation, or c) post-menopausal for at least 12 months before start of study
    •Age between 18 and 55 years at screening (both inclusive)
    •No clinically relevant history of cardiovascular (including arrhythmias) disease; no active hyperthyroidism
    •No clinically relevant history of chronic or malignant diseases (except for in situ basalioma)
    •Body mass index (BMI) between 18 and 33 kg/m2 (both inclusive)
    •Systolic blood pressure (SBP) 100-155 mmHg, diastolic blood pressure (DBP) 50-90 mmHg, and heart rate (HR) 45-90 beats per min (inclusive), measured on the arm with the highest blood pressure after resting for 5 min in the supine position
    •No clinically significant findings on physical examination other than allergy and mild to moderate persistent asthma
    •12-lead ECG without clinically relevant abnormalities
    •No recent respiratory tract infections (within 3 weeks of screening and during study)
    •Non-smokers or ex-smokers (stopped for at least 6 months before screening, and <10 pack-years)
    •No history of anaphylaxis, or of severe food or medication allergy
    •Haematology, clinical chemistry and urinalysis test results not deviating from the normal range to a clinically relevant extent as deemed by the investigator
    •Negative results from urine drug and cotinine screens (for nicotine use)
    •Negative screening for Hepatitis B, Hepatitis C and HIV
    •Ability to communicate well with the investigator and to understand and comply with the requirements of the study
    •Documented history of mild to moderate persistent asthma, first diagnosed by an MD at least 6 months prior to the screening visit and currently controlled by beta-agonists on an “as needed” basis only
    •Clinically stable asthma, i.e. stable asthma symptoms and baseline prebronchodilator FEV1 values within 10% (i.e. study day 1 compared to screening) (preferably measured at the same time of day ±3 h); stable use of “as needed” Short-Acting Beta2 Agonist (SABA) but not on controller medication (see exclusion criteria)
    •Pre-bronchodilator FEV1 ≥70% of predicted
    •Documented bronchial hyperresponsiveness to inhaled Methacholine (MBr or MCh) with a PC20Meth of ≤8 mg/mL at screening
    •Documented allergy by a standardized Skin Prick Test (SPT): i.e. a positive wheal response to one or more of the common airborne allergens: Grass or tree Pollen, House Dust Mite, D. Farinae, cat, dog, or horse-dander, Aspergillus Fumigatus, A. Alternata, Artemisia Vulgaris (in the past 1 year)
    •Steroid-naïve, or not on inhaled/nasal corticosteroids for at least one month and 8 weeks of systemic therapy before the study
    •No use of anti-IgE (omalizumab) in the past 6 months
    •No systemic or aerosol use of the following: leukotriene receptor antagonists (LTRA), theophylline, long acting beta agonists (LABA), or antihistamine such as H1 receptor antagonist for 2 weeks before the study
    •No nasal medications (steroids, antihistamines, cromones) for one month (for nasal steroids), or 2 weeks for other medications; xylomethazoline (1 week); nasal NaCl 0.9% allowed
    •Signed informed consent
    E.4Principal exclusion criteria
    •Desensitization therapy in the past 5 years
    •Severe exacerbation requiring hospital evaluation and/or admission in the past 2 years
    •Unstable/uncontrolled disease within 3 weeks of participation in the study
    •History or clinical evidence of any disease and/or existence of any surgical or medical condition which might interfere with the absorption, distribution, metabolism or excretion of the study drug
    •Treatment with another investigational drug within 3 months prior to screening
    •Known hypersensitivity to any excipients of the drug formulations
    •History or clinical evidence of alcoholism within the 3-year period prior to screening (i.e. regular use of more than 21 units of alcohol/week for males and more than 14 units/week for females)
    •Excessive caffeine consumption, defined as > 8 cups/per day at screening – unable to discontinue caffeine consumption for at least 8 h before and during the testing
    •History or any other clinical condition, judged to be a contraindication for participation in the study as judged by the PI
    •Loss of 250 mL or more of blood within 3 months prior to screening
    •Any abnormalities on lab or urine results outside the normal range, deemed clinically significant by the investigator (and with written consent of the sponsor)
    E.5 End points
    E.5.1Primary end point(s)
    A)Respiratory safety (i.e., effects on the upper and lower airways):
    -upper airways (nose): local irritation, sneezing, prolonged rhinorrhea, nasal congestion;
    -throat: local irritation, redness, dryness, effect on the voice;
    -lower airways (lung): coughing, dyspnoea/wheeze, clinically relevant decreases in breathing frequency and/or peripheral oxygen saturation (measured by pulse-oximetry during nebulisation) and/or decreases in spirometry (FEV1).
    B) Gastrointestinal safety/tolerability (i.e., nausea, vomiting, and abdominal discomfort or pain and/or diarrhoea).
    C) Cardiovascular safety (i.e., clinically relevant effects on heart rate & rhythm, and conduction times; and sitting blood pressure (also see relevant section 6.1.1 on cardiovascular safety)
    -12-lead ECG and holter ECG (rhythm and conduction times- with particular care given to the QTc interval) at baseline, during dosing and at regular intervals up to approximately 12 h;
    -ECG telemetry during nebulisation up to approximately 2 h post-dosing;
    -Sitting blood pressure and heart rate at baseline and at regular intervals (approximately 5-10 min) during nebulisation up to 1 h post-dosing and subsequently at approximately 15 min intervals up to 4 h post-dosing, followed by hourly intervals to 12 hours, and at approximately 24 h; Additional standing blood pressure measurements (within 2 minutes of sitting blood pressure measurements) will be collected at 15 min, 45 min and 2 h post-dosing for 12X dose and at 30 min, 60 min, and 2 h post-dosing for 24X dose.
    D) Blood chemistry safety by standard clinical assessment at baseline and at 24 h post-dosing
    E) Full hematological assessment (i.e., cell counts and coagulation status) at baseline, and at approximately 35 min and 24 h post-dosing.
    F) Symptoms and any adverse events throughout the study
    G) Subjective tolerability (i.e., taste, aftertaste, and smell as well as nasal irritation) throughout the study
    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 Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    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) Yes
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    Dose finding
    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 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.8.3 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.8.5The 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 Information not present in EudraCT
    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
    Last follow-up visit of the last subject entered into the study will be the end of study.
    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 months0
    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.1.3Elderly (>=65 years) No
    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 state20
    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 Decision2010-10-21
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2010-11-08
    P. End of Trial
    P.End of Trial StatusCompleted
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