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    Summary
    EudraCT Number:2014-003947-36
    Sponsor's Protocol Code Number:NT2014/Orv/Prot001
    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:2014-10-23
    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 number2014-003947-36
    A.3Full title of the trial
    Evaluation of orvepitant in an exploratory open-label clinical study in chronic treatment-refractory cough
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study to evaluate the efficacy of the drug orvepitant at one dose level (30 mg every day) to reduce the urge to cough in patients suffering from chronic (long-term) cough that is resistant to treatment.

    This means all the patients on the study will receive orvepitant (it is an ‘open-label’ trial), so they and the Investigator will know they are taking the investigational medication.
    A.3.2Name or abbreviated title of the trial where available
    VOLCANO-1 Study
    A.4.1Sponsor's protocol code numberNT2014/Orv/Prot001
    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 SponsorNeRRe Therapeutics Ltd
    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 supportNeRRe Therapeutics Ltd
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationUniversity of Manchester
    B.5.2Functional name of contact pointHead of Cough Research
    B.5.3 Address:
    B.5.3.1Street Address2nd Floor, ERC
    B.5.3.2Town/ cityWythenshawe Hospital, Southmoor Rd
    B.5.3.3Post codeM23 9LT
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number01612915879
    B.5.5Fax number01612915730
    B.5.6E-mailjacky.smith@manchester.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 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 nameOrvepitant
    D.3.2Product code GW823296
    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.3.8INN - Proposed INNOrvepitant
    D.3.9.1CAS number 579475-24-4
    D.3.9.2Current sponsor codeGW823296
    D.3.9.4EV Substance CodeAS1
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number30
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Chronic treatment-refractory cough
    E.1.1.1Medical condition in easily understood language
    Chronic cough
    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 17.1
    E.1.2Level LLT
    E.1.2Classification code 10066656
    E.1.2Term Chronic cough
    E.1.2System Organ Class 100000004855
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the change in objectively recorded daytime cough frequency in chronic treatment-refractory cough patients at Week 4 after treatment with orvepitant (30 mg given once daily [od], orally).
    E.2.2Secondary objectives of the trial
    • To evaluate the change in objectively recorded daytime cough frequency in chronic treatment-refractory cough patients at Week 1 after treatment with orvepitant and at Follow-up at Week 8.

    • To evaluate the change in objectively recorded night-time cough frequency in chronic treatment-refractory cough patients at Week 1 and Week 4 after treatment with orvepitant and at Follow-up at Week 8.

    • To evaluate the change in the Cough-specific Quality of Life Questionnaire (CQLQ) score at Weeks 1 and 4 after treatment with orvepitant and at Follow-up at Week 8.

    • To record the Global Rating of Change for Cough Frequency and Severity at Weeks 1 & 4 after treatment with orvepitant and at Follow-up at Week 8.

    • To evaluate the daily and weekly change in Cough Severity Visual Analogue Scale (VAS) after treatment with orvepitant to Week 4 and up to Follow-up at Week 8.

    • To assess the safety and tolerability of orvepitant for 4 weeks.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    • Male and female subjects 18-75 years of age
    • Able to understand and comply with the requirements of the study and sign Informed Consent forms.
    • Females must be non-pregnant and non-lactating with no intention of pregnancy during study treatment
    • WOCP (not >1 year post-menopausal) must have a negative blood serum pregnancy test performed at the Screening visit and agree to use one of the following acceptable birth control methods:
    o Surgical sterilization of either the female subject in study (e.g., bilateral tubal ligation) or of her male partner (vasectomy with documented azoospermia) if he is the sole partner of that subject
    o Established hormonal contraception (implantable, patch, oral or intramuscular [IM]) administered for at least one month prior to study medication administration
    o An intrauterine device (IUD) or intrauterine system (IUS) with failure rate of less than 1% per year inserted by qualified physician at least one month prior to study medication administration
    o Double barrier method: condom and occlusive cap (diaphragm) with spermicidal foam/ gel/ film/ cream/ pessary
    • No clinically significant abnormal chest radiology in the opinion of the Investigator
    • Lung function defined by both the FEV1 and FVC >70% predicted, measured using spirometry
    • Diagnosis of chronic treatment-refractory cough based on a minimum of >3 months of symptoms. Chronic treatment-refractory cough (also called chronic idiopathic cough or chronic treatment-resistant cough), defined as a cough for which either no objective evidence of an underlying trigger can be determined after routine clinical investigation (idiopathic) or a cough that did not respond to standard treatment for identified underlying triggers (treatment-resistant).
    • A daytime cough frequency of >3 and a maximum of <250 coughs/ hour, as assessed using an ACM for 24 hours at screening.
    • Concomitant respiratory medication is allowed, but patients must be stable on such medication and take it for the duration of the study.
    E.4Principal exclusion criteria
    • Subjects with recent respiratory tract infection (< 4 weeks prior to study start)
    • Females who are breast feeding or pregnant
    • Current smokers or ex-smokers with < 6 months abstinence or cumulative history of >10 pack years
    • Treatment with Angiotensin Converting Enzyme (ACE) inhibitors within 3 months of study-start
    • Current drug or alcohol abuse
    • Uncontrolled hypertension (i.e., > 150/100 mmHg despite adequate medical therapy)
    • Recent myocardial infarction, or history of congestive cardiac failure.
    • Subjects with prior renal transplant, current renal dialysis, with creatinine clearance <30mL/ min or history of renal tubular acidosis
    • Severe hepatic impairment
    • Any clinically significant neurological disorder
    • Any clinically significant or unstable medical or psychiatric condition that would interfere with the patient's ability to participate in the study
    • Subjects with a prior medical history of or an increased risk of seizures, or who have a history of recent head trauma that resulted in a loss of consciousness or concussion
    • Any invasive malignancy in the past 2 years
    • Any clinically significant abnormal laboratory test result(s):
    a. Serum creatinine laboratory value greater than 1.5 x upper limit of normal (ULN) reference range (after adjustment for age) or estimated creatinine clearance <60 mL/ min.
    b. Total bilirubin greater than upper limit of normal reference range (with the exception of Gilbert's Syndrome) and/ or alanine transaminase (ALT) >1.5 times upper limit of normal reference ranges (after adjustment for age).
    • The use of opioids, anticonvulsants or tricyclic antidepressants because these may affect cough reflex sensitivity. Subjects currently taking drugs in these classes for chronic cough must have them discontinued at least 2 weeks prior to entry into the study.
    • Participation in any clinical research study evaluating another investigational drug or therapy within 30 days or within 5 half-lives (whichever is longer), of the investigational drug prior to consenting to study entry. If the subject is in an observational clinical study no washout is required.
    • Subjects receiving aprepitant (Emend®) or fosaprepitant (Ivemend®), NK-1 antagonists licensed as anti-emetics within 4 weeks of the Screening visit
    • Subjects who, in the opinion of the Investigator, should not participate in the study for any other reason.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint will be the change in objective daytime cough frequency at Week 4 compared to Baseline.
    E.5.1.1Timepoint(s) of evaluation of this end point
    This endpoint will be calculated from the baseline cough frequency and the cough frequency on the final day of 4 weeks treatment.
    E.5.2Secondary end point(s)
    • Change in objective daytime cough frequency at Weeks 1 and 8 compared to Baseline
    • Change in objective daytime cough frequency at Week 8 compared to Week 4
    • Change in objective night-time cough frequency at Weeks 1, 4 and 8 compared to Baseline
    • Change in objective night-time cough frequency at Week 8 compared to Week 4
    • Change in the CQLQ score at Weeks 1, 4 and 8 compared to Baseline
    • Change in the CQLQ score at Week 8 compared to Week 4
    • Global Rating of Change for Cough Frequency and Severity Scale at Weeks 1, 4 and 8
    • Cough Severity VAS at Baseline (calculated as the average of the readings recorded between the Screening and Baseline visits) and at each day and week (based on the average of the readings recorded in each week)
    E.5.2.1Timepoint(s) of evaluation of this end point
    As described above.
    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 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 Yes
    E.6.13.1Other scope of the trial description
    Quality of life
    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) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    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) Information not present in EudraCT
    E.8.2.2Placebo Information not present in EudraCT
    E.8.2.3Other Information not present in EudraCT
    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.8.4.1Number of sites anticipated in Member State concerned1
    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 months0
    E.8.9.1In the Member State concerned days1
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days1
    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: 10
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 5
    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 state15
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 15
    F.4.2.2In the whole clinical trial 15
    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)
    All study participants will receive normal clinical care on completion of the trial. It will be made clear to patients that even if the study medication made a difference to their cough during the trial, once trial treatment has finished, the medication will not be made available at the end of the study.
    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 Decision2015-01-12
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2014-10-20
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2015-10-26
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