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    The EU Clinical Trials Register currently displays   42869   clinical trials with a EudraCT protocol, of which   7063   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2019-001699-12
    Sponsor's Protocol Code Number:205019
    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:2019-07-30
    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 number2019-001699-12
    A.3Full title of the trial
    An open-label, randomized three period cross-over relative bioavailability study to compare the pharmacokinetic parameters of a lower dose formulation of ambrisentan (GSK1325760) with marketed ambrisentan in healthy adult participants
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Relative bioavailability study of marketed and lower dose ambrisentan in healthy adult participants
    A.4.1Sponsor's protocol code number205019
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorGlaxoSmithKline Research and Development 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 supportGlaxoSmithKline Research & Devlopment Ltd
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationGlaxoSmithKline Research & Development Ltd
    B.5.2Functional name of contact pointGSK Clinical Support Help Desk
    B.5.3 Address:
    B.5.3.1Street Address1-3 Iron Bridge Road, Stockley Park West
    B.5.3.2Town/ cityUxbridge, Middlesex
    B.5.3.3Post codeUB11 1BT
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number+44 (0)80 0 783 9733
    B.5.5Fax numberNot applicable
    B.5.6E-mailGSKClinicalSupportHD@gsk.com
    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 nameAmbrisentan Tablet
    D.3.2Product code GSK1325760
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation Yes
    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 INNAMBRISENTAN
    D.3.9.1CAS number 177036-94-1
    D.3.9.3Other descriptive name(S)-2-(4,6-dimethylpyrimidin-2-yloxy)-3-methoxy-3,3-diphenylpropanoic acid
    D.3.9.4EV Substance CodeSUB25424
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1
    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.IMP: 2
    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.2.1.1.1Trade name Volibris
    D.2.1.1.2Name of the Marketing Authorisation holderGlaxo Group Ltd
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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 nameAmbrisentan 5mg film-coated tablets [marketed product]
    D.3.4Pharmaceutical form Film-coated 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 INNAMBRISENTAN
    D.3.9.1CAS number 177036-94-1
    D.3.9.3Other descriptive name(S)-2-(4,6-dimethylpyrimidin-2-yloxy)-3-methoxy-3,3-diphenylpropanoic acid
    D.3.9.4EV Substance CodeSUB25424
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Pulmonary arterial hypertension
    E.1.1.1Medical condition in easily understood language
    Pulmonary arterial hypertension (a narrowing of the arteries connecting the lungs to the heart that leads to an increase in blood pressure)
    E.1.1.2Therapeutic area Diseases [C] - Cardiovascular Diseases [C14]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10064911
    E.1.2Term Pulmonary arterial hypertension
    E.1.2System Organ Class 10038738 - Respiratory, thoracic and mediastinal disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To compare the relative bioavailability of AMB (1 mg x 5 tablets) administered as tablets dispersed in water or administered orally, with marketed AMB (5 mg x 1 tablet) administered orally, in healthy adult participants under fasted conditions.
    E.2.2Secondary objectives of the trial
    To monitor the safety and tolerability of AMB (1 mg x 5 tablets) administered as tablets dispersed in water or administered orally, compared with marketed AMB
    (5 mg x 1 tablet) administered orally, in healthy adult participants.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Participants are eligible to be included in the study only if all of the following criteria apply:
    1. Participant must be 18 to 65 years of age inclusive, at the time of signing the informed consent
    2. Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, vital signs and cardiac monitoring (refer to Section 5.4 for information about rescreening).
    3. Average systolic blood pressure between 100-160 mmHg and diastolic between 55-90 mmHg (inclusive) over 3 readings at screening
    4. Body weight >50 kg for men and ≥ 45kg for women, and body mass index (BMI) within the range 18-30 kg/m2 (inclusive).
    5. Male or Female
    a. Male Participants
    Male participants are eligible to participate if they agree to the following during the study and for at least 13 weeks afterwards corresponding to time needed to eliminate study intervention (5 terminal half-lives) plus an additional 90 days (a spermatogenesis cycle):
    ●Refrain from donating sperm
    PLUS either:
    ●Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent
    OR
    ●Must agree to use contraception/barrier, as follows:
    ●Agree to use a male condom; and
    ●Female partner to use an additional highly effective contraceptive method with a failure rate of <1% per year as described in Appendix 4 of the study protocol.
    b. Female participants
    A female participant is eligible to participate if she is not a woman of childbearing potential (WOCBP), as defined in Appendix 4 of the study protocol
    6. Capable of giving signed informed consent as described in Appendix 1 of the study protocol which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
    E.4Principal exclusion criteria
    Participants are excluded from the study if any of the following criteria apply:
    1. History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, haematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention or interfering with the interpretation of data
    2. History or presence of palpitations or tachyarrhythmias
    3. Haemoglobin (Hb) below the normal range (Hb <133 g/L for male participants; and Hb <114 g/L for female participants)
    4. Alanine transaminase (ALT) >1.5x upper limit of normal (ULN)
    5. Bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)
    6. Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
    7. QTc >450 msec
    NOTES:
    ●The QTc is the QT interval corrected for heart rate according to Bazett’s formula (QTcB), Fridericia’s formula (QTcF), and/or another method, machine-read or manually over-read.
    ●The specific formula that will be used to determine eligibility and discontinuation for an individual subject should be determined prior to initiation of the study. In other words, several different formulae cannot be used to calculate the QTc for an individual subject and then the lowest QTc value used to include or discontinue the subject from the trial.
    8. Past or intended use of over-the-counter or prescription medication (including vitamins and dietary or herbal supplements but excluding paracetamol ≤2 g/day) within 7 days (or 14 days if the drug is a potential enzyme inhibitor) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless approved by the Investigator in conjunction with GSK Medical Monitor.
    9. Participation in the study would result in loss of blood or blood products in excess of 500 mL within a 56-day period
    10. Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day
    11. Current enrolment or past participation within 30 days before screening in any other clinical study involving an investigational study intervention or any other type of medical research
    12. Presence of Hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to first dose of study intervention
    13. Positive Hepatitis C antibody test result at screening or within 3 months prior to first dose of study intervention.
    NOTE: Subjects with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C RNA test is obtained
    14. Positive Hepatitis C RNA test result at screening or within 3 months prior to first dose of study intervention.
    NOTE: Test is optional and subjects with negative Hepatitis C antibody test are not required to also undergo Hepatitis C RNA testing
    15. Positive human immunodeficiency virus (HIV) antibody test
    16. Positive pre-study drug/alcohol screen
    17. Regular use of known drugs of abuse
    18. Regular alcohol consumption within 6 months prior to the study defined as:
    ●An average weekly intake of >14 units. One unit is equivalent to 8 g of alcohol: a half-pint (~240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
    19. Smoking > 5 cigarettes per week (or equivalent) and participants must be able to abstain from smoking for a 24-hour period prior to dose and any time whilst in the clinical unit.
    20. Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study
    E.5 End points
    E.5.1Primary end point(s)
    Plasma pharmacokinetic parameters of AMB, as data permit: Cmax, tmax, AUC (0-∞), AUC(0-t) and t½.
    E.5.1.1Timepoint(s) of evaluation of this end point
    PK samples collected at the following timepoints in each treatment period: Pre-dose, Post dose (hrs); 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48, 72.
    E.5.2Secondary end point(s)
    Adverse events (AE), vital signs, electrocardiogram (ECG), and clinical laboratory values.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Adverse Events will be continually assessed throughout the study and at follow up.
    Vital signs will be assessed at the following timepoints: Pre-dose, Post-dose (hrs); 0.5, 1, 2, 4, 8, 12, 24, 48, 72.
    ECG’s will be conducted at the following timepoints: Pre-dose, Post-dose (hrs); 1, 2, 4, 12, 24, 72.
    Clinical chemistry, hematology and urinalysis values will be collected at the following timepoints: Day -1 (admission to unit) and 48 post dose. Additional tests may be performed at any time during the study as determined necessary by the investigator.
    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 No
    E.6.6Pharmacokinetic Yes
    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) 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
    Bioavailability of lower dose formulation
    E.7.2Therapeutic exploratory (Phase II) No
    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 Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over Yes
    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 trial3
    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 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 years0
    E.8.9.1In the Member State concerned months2
    E.8.9.1In the Member State concerned days7
    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: 22
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 2
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers Yes
    F.3.2Patients No
    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 state24
    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)
    As this is a healthy participant study, no intervention will be given to participants following the end of study. Participants will receive a follow up visit 7–14 days after their last dose.
    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 Decision2019-08-20
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-08-27
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2019-12-17
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