Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   44258   clinical trials with a EudraCT protocol, of which   7344   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).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2012-001642-17
    Sponsor's Protocol Code Number:AMB116457
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2013-09-12
    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 ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2012-001642-17
    A.3Full title of the trial
    An open-label extension study of the long-term safety, tolerability and efficacy of ambrisentan in subjects with inoperable chronic thromboembolic pulmonary hypertension (CTEPH)
    Studio di estensione in aperto sulla sicurezza, la tollerabilità e l’efficacia a lungo termine di Ambrisentan in soggetti con ipertensione polmonare cronica tromboembolica (IPCT) non operabile.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    An extension study of a drug to treat Inoperable Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
    Studio di estensione di un farmaco per trattare l’ ipertensione polmonare cronica tromboembolica (IPCT) non operabile
    A.4.1Sponsor's protocol code numberAMB116457
    A.5.4Other Identifiers
    Name:AmbrisentanNumber:AMB116457
    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 SponsorGlaxoSmithKline Research & Developement 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 supportGSK Pharma and R&D
    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 pointClinical Trials HelpDesk
    B.5.3 Address:
    B.5.3.1Street AddressIron Bridge Road
    B.5.3.2Town/ cityUxbridge
    B.5.3.3Post codeUB11 1BU
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number+440208990 4466
    B.5.5Fax number+4402081234
    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 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 Yes
    D.2.5.1Orphan drug designation numberEU/3/05/273
    D.3 Description of the IMP
    D.3.1Product nameAmbrisentan
    D.3.2Product code GSK1325760
    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.3.9.2Current sponsor codeGSK1325760
    D.3.9.3Other descriptive nameAmbrisentan
    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
    Subjects with inoperable Chronic Thromboembolic Pulmonary
    Hypertension (CTEPH)
    E.1.1.1Medical condition in easily understood language
    Inoperable chronic thromboembolic pulmonary hypertension
    E.1.1.2Therapeutic area Diseases [C] - Blood and lymphatic diseases [C15]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 17.0
    E.1.2Level LLT
    E.1.2Classification code 10068739
    E.1.2Term Chronic thromboembolic pulmonary hypertension
    E.1.2System Organ Class 100000004855
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective is the long-term safety and tolerability of Ambrisentan in the CTEPH population (see Safety).

    Safety assessments
    - Adverse Events;
    - Serious Adverse Events;
    - Clinical laboratory parameters (including liver safety and haematological parameters);
    - Physical examination (including jugular venous pressure, liver size, peripheral oedema, ascites and signs of deep vein thrombosis);
    - Vital Signs (including body mass index at the entry visit only);
    - The time to change in dose of Ambrisentan or other targeted PAH therapeutic agents (prostanoids, PDE-5 inhibitors) due to tolerability issues (e.g. adverse events).
    E.2.2Secondary objectives of the trial
    Efficacy assessments
    - 6 minute walking distance (6MWD) test evaluated every 3 months;
    - WHO functional class every 3 months;
    - Borg CR10 Scale (BCR10S) immediately following exercise, every 3 months;
    - Clinical worsening of CTEPH as defined by the time from randomization to the first occurrence of events (see section 2.2.1 of protocol - page 18);
    - Addition of another targeted PAH therapeutic agents (prostanoids, PDE-5 inhibitors) due to reasons outlined in protocol (see section 2.2.1 - page 18);
    - Change in dose of Ambrisentan or other targeted PAH therapeutic agents (prostanoids, PDE-5 inhibitors) due to deterioration of clinical condition;
    - Subject Global Assessment every three months using the Short Form 36 Health Survey (SF-36)
    - N-terminal pro-B-type natriuretic peptide (NT-Pro BNP) concentration every 3 months.

    Other
    - Refer to Section 2.2.2 of the Protocol (pages 19 and 50)
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Subjects eligible for enrolment in the study must meet all of the following criteria:
    a) Have been randomized to the protocol for AMB115811.
    b) Have completed the Week 16 visit in AMB115811.

    General considerations:
    c) Female subject of childbearing potential must agree to use 2 reliable methods
    of contraception from the Screening Visit until study completion and for at
    least 30 days following the last dose of Investigational Product (reliable
    methods of contraception are described in Appendix 2). As part of the
    consent, female subjects of childbearing potential will be informed of the risk
    of teratogenicity and will need to be counseled in a developmentally
    appropriate manner on the importance of pregnancy prevention; and male
    subjects will need to be informed of potential risk of testicular tubular atrophy
    and aspermia.
    d) Subject must agree not to participate in a clinical study involving another
    investigational drug or device throughout this study.
    e) Subject must be competent to understand the information given in the
    Institutional Review Board (IRB) or Independent Ethics Committee (IEC)
    approved informed consent form (ICF) and must sign the form prior to the
    initiation of any study procedures.
    Specific information regarding warnings, precautions, contraindications, adverse events, and other pertinent information on the GSK investigational product or other study treatment that may impact subject eligibility is provided in the Investigators Brochure and product label for PAH indication.
    Deviations from inclusion criteria are not allowed because they can potentially jeopardize the scientific integrity of the study, regulatory acceptability or subject safety. Therefore, adherence to the criteria as specified in the protocol is essential.
    E.4Principal exclusion criteria
    Subjects meeting any of the following criteria must not receive Ambrisentan, however
    may still be followed-up as part of the study and be treated according to best clinical
    practice as decided by the investigator:
    1. Subject prematurely withdrew from AMB115811where IP has been stopped due
    to safety , efficacy or any other reason at the opinion of the investigator,
    2. Subject has a known hypersensitivity to the Investigational Products, the
    metabolites, or formulation excipients
    3. Female subjects who are pregnant or breastfeeding or no-longer agree to comply with using effective contraception as defined in Appendix 2 of the protocol
    4. Subjects with ALT and/or AST ≥ 3xULN
    5. Subjects with bilirubin ≥ 2xULN (with>35% direct bilirubin)
    6. Subjects with severe renal impairment (estimated creatinine clearance <30
    mL/min assessed within the previous 45 days) at the point of transition from
    Study AMB115811
    7. Subject has moderate - severe hepatic impairment (Child-Pugh class B-C with or
    without cirrhosis) at the point of transition from study AMB115811
    8. Subject with clinically significant fluid retention in the opinion of the investigator
    9. Subject with clinically significant anemia in the opinion of the investigator
    10. Subjects who are to enter another clinical trial or be treated with another
    investigational product after exiting Study AMB115811.
    Deviations from exclusion criteria are not allowed because they can potentially
    jeopardize the scientific integrity of the study, regulatory acceptability or subject safety.
    Therefore, adherence to the criteria as specified in the protocol is essential.
    E.5 End points
    E.5.1Primary end point(s)
    The primary objective is the long-term safety and tolerability of ambrisentan in the CTEPH population (see safety).

    Safety
    - Adverse Events;
    - Serious Adverse Events;
    - Clinical laboratory parameters (including liver safety and haematological parameters);
    - Physical examination (including jugular venous pressure, liver size, peripheral oedema, ascites and signs of deep vein thrombosis);
    - Vital Signs (including body mass index at the entry visit only);
    - The time to change in dose of Ambrisentan or other targeted PAH therapeutic agents (prostanoids, PDE-5 inhibitors) due to tolerability issues (e.g. adverse events).
    E.5.1.1Timepoint(s) of evaluation of this end point
    Monthly, every 3 months, every 6 months and follow-up visits.
    E.5.2Secondary end point(s)
    Efficacy

    • The change from Study AMB115811 baseline and week 16 visits in the 6 minute walking distance (6MWD) test evaluated every three months;

    • The change from Study AMB115811 baseline and week 16 visits in WHO functional class every three months;

    • The change from Study AMB115811 baseline and week 16 visits in Borg CR10 Scale (BCR10S) immediately following exercise, every three months;

    • Clinical worsening of CTEPH as defined by the time from randomization to the first occurrence of
    a) Death
    b) Lung transplantation
    c) Hospitalization for worsening CTEPH
    d) Atrial septostomy
    e) Addition of parenteral prostanoids
    f) Appearance of two or more CTEPH worsening events*;
    *Worsening events to consider:
    1. A decrease from baseline of at least 20 percent in the distance walked during the six-minute walk test;
    2. An increase of one or more WHO Functional Class;
    3. Worsening right ventricular failure (e.g., as indicated by increased jugular venous pressure, new/worsening hepatomegaly, ascites, or peripheral edema; worsening echocardiographic parameters such as tricuspid annulus plane systolic excursion (TAPSE) and TDI of the tricuspid annulus);
    4. Rapidly progressing cardiogenic, hepatic, or renal failure;
    5. Refractory systolic hypotension (systolic blood pressure less than 85 mmHg).
    Clinical Worsening events will be independently adjudicated.

    • The time to addition of another targeted PAH therapeutic agents (prostanoids, PDE-5 inhibitors) due to the following reasons:
    ­- Deterioration of clinical condition;
    ­- Lack of beneficial effect with previous therapy (not reaching set treatment goals);

    • The time to change in dose of ambrisentan or other targeted PAH therapeutic agents (prostanoids, PDE-5 inhibitors) due to deterioration of clinical condition;

    • The change from Study AMB115811 baseline and week 16 visits in Subject Global Assessment every three months using the Short Form 36 Health Survey (SF-36)

    • Change from Study AMB115811 baseline and week 16 visits in N-terminal pro-B-type natriuretic peptide (NT-Pro BNP) concentration every three months.

    Other
    • The change from Study AMB115811 baseline and week 16 visits cardiopulmonary hemodynamic assessments data in subjects in whom hemodynamic data is considered part of the standard of care.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Monthly, every 3 months, every 6 months and follow-up visits
    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 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) 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) Yes
    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 Yes
    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) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial1
    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 Yes
    E.8.5.1Number of sites anticipated in the EEA23
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Argentina
    Brazil
    Canada
    China
    Israel
    Japan
    Korea, Democratic People's Republic of
    Mexico
    Russian Federation
    Turkey
    United States
    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
    LSLV
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years5
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years5
    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.1.2.1Number of subjects for this age range: 80
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 80
    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 state8
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 65
    F.4.2.2In the whole clinical trial 160
    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)
    Subjects can remain in this study until one of the following conditions is met:
    - The product is approved locally for use in inoperable CTEPH patients;
    - Development for use in the CTEPH population is discontinued or product is not approved locally;
    - The investigator decides to discontinue the subject or subject decides to discontinue from the study.

    For full details, please refer to Section 5.7 of the protocol (page 24).
    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 Decision2014-08-06
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2014-07-15
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA