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 are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   42771   clinical trials with a EudraCT protocol, of which   7044   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 in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .

    Clinical Trials marked as "Trial now transitioned" were transitioned to the Clinical Trial Regulation 536/2014 and can be further followed in the Clinical Trial Information System  
     
    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

    Download PDF

    Clinical Trial Results:
    A Prospective, Multicenter, Single-arm, Open-label, Phase 4 Study to Evaluate the Effects of Macitentan on Right vEntricular Remodeling in Pulmonary ArterIal HypeRtension Assessed by Cardiac Magnetic Resonance Imaging

    Summary
    EudraCT number
    2014-004066-20
    Trial protocol
    GB   NL   DE   IT  
    Global end of trial date
    08 Aug 2019

    Results information
    Results version number
    v1(current)
    This version publication date
    20 Sep 2020
    First version publication date
    20 Sep 2020
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    AC-055-403
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02310672
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Actelion Pharmaceutical Ltd.
    Sponsor organisation address
    Gewerbestrasse 16, Allschwil, Switzerland, 4123
    Public contact
    Global Medical Information, Actelion Pharmaceutical Ltd., medinfo@actelion.com
    Scientific contact
    Global Medical Information, Actelion Pharmaceutical Ltd., medinfo@actelion.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    08 Aug 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    08 Aug 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The purpose of the study is to evaluate the effect of macitentan on right ventricular and on hemodynamic properties in subjects with symptomatic pulmonary arterial hypertension (PAH).
    Protection of trial subjects
    This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Clinical Practices and applicable regulatory requirements. Safety was evaluated based on adverse events (AEs), clinical laboratory tests (hematology, serum chemistry, coagulation tests, and pregnancy test), vital sign measurements, and physical examinations.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    25 Jun 2015
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Ethical reason
    Long term follow-up duration
    13 Months
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Germany: 12
    Country: Number of subjects enrolled
    France: 14
    Country: Number of subjects enrolled
    United Kingdom: 3
    Country: Number of subjects enrolled
    Hong Kong: 7
    Country: Number of subjects enrolled
    Israel: 2
    Country: Number of subjects enrolled
    Italy: 3
    Country: Number of subjects enrolled
    Malaysia: 8
    Country: Number of subjects enrolled
    Netherlands: 12
    Country: Number of subjects enrolled
    Russian Federation: 11
    Country: Number of subjects enrolled
    Singapore: 9
    Country: Number of subjects enrolled
    United States: 6
    Worldwide total number of subjects
    87
    EEA total number of subjects
    44
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    75
    From 65 to 84 years
    12
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    Total of 112 subjects was screened out of them 89 subjects were enrolled in the study and 87 subjects received study medication. Two subjects who did not receive study treatment were wrongly classified as enrolled by the sites.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    Not blinded

    Arms
    Arm title
    Macitentan 10 mg
    Arm description
    Subjects received macitentan 10 milligrams (mg) tablets once daily until the premature discontinuation of study drug or end of treatment (EOT) on the day of the last dose of study drug at Week 52.
    Arm type
    Experimental

    Investigational medicinal product name
    Macitentan
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received Macitentan 10 mg tablets once daily.

    Number of subjects in period 1
    Macitentan 10 mg
    Started
    87
    Completed
    72
    Not completed
    15
         Adverse event, serious fatal
    1
         Consent withdrawn by subject
    1
         Sponsor decision
    12
         Lost to follow-up
    1

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Macitentan 10 mg
    Reporting group description
    Subjects received macitentan 10 milligrams (mg) tablets once daily until the premature discontinuation of study drug or end of treatment (EOT) on the day of the last dose of study drug at Week 52.

    Reporting group values
    Macitentan 10 mg Total
    Number of subjects
    87 87
    Title for AgeCategorical
    Units: subjects
        Children (2-11 years)
    0 0
        Adolescents (12-17 years)
    0 0
        Adults (18-64 years)
    75 75
        From 65 to 74 years
    12 12
        75 years and over
    0 0
    Title for AgeContinuous
    Units: years
        arithmetic mean (standard deviation)
    45.9 ± 14.48 -
    Title for Gender
    Units: subjects
        Female
    70 70
        Male
    17 17

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Macitentan 10 mg
    Reporting group description
    Subjects received macitentan 10 milligrams (mg) tablets once daily until the premature discontinuation of study drug or end of treatment (EOT) on the day of the last dose of study drug at Week 52.

    Primary: Change From Baseline in Right Ventricular Stroke Volume (RVSV) at Week 26

    Close Top of page
    End point title
    Change From Baseline in Right Ventricular Stroke Volume (RVSV) at Week 26 [1]
    End point description
    Change from baseline in RVSV assessed by cardiac magnetic resonance imaging (MRI) from pulmonary artery flow was reported at Week 26. The primary analysis was based on interim results as pre-planned and the primary outcome measures data table reported is finalized as is. The Modified full analysis set (mFAS) included all screened subjects who received at least one dose of the study drug and who had a baseline as well as a post-baseline measurement taken between 16 weeks and 30 weeks of treatment.
    End point type
    Primary
    End point timeframe
    Baseline and Week 26
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive statistics were done, no inferential statistical analyses were performed.
    End point values
    Macitentan 10 mg
    Number of subjects analysed
    42
    Units: Milliliters (mL)
        least squares mean (standard error)
    15.17 ± 2.75
    No statistical analyses for this end point

    Primary: Ratio of Week 26 to Baseline Pulmonary Vascular Resistance (PVR)

    Close Top of page
    End point title
    Ratio of Week 26 to Baseline Pulmonary Vascular Resistance (PVR) [2]
    End point description
    Ratio of Week 26 to baseline PVR as assessed by RHC was reported. PVR represents the resistance against which the right ventricle needs to pump. PVR is determined by right heart catheterization (RHC). PVR was calculated as 80*(Mean pulmonary arterial pressure [mPAP] –[Pulmonary capillary wedge pressure {PCWP} or Left ventricular end diastolic pressure {LVEDP} if PCWP not available/cardiac output [CO]). The primary analysis was based on interim results as pre-planned and the primary outcome measures data table reported is finalized as is. mFAS included all screened subjects who received at least one dose of study drug and who had a baseline as well as a post-baseline measurement taken between 16 weeks and 30 weeks of treatment.
    End point type
    Primary
    End point timeframe
    Baseline and Week 26
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive statistics were done, no inferential statistical analyses were performed.
    End point values
    Macitentan 10 mg
    Number of subjects analysed
    42
    Units: Ratio
        geometric mean (geometric coefficient of variation)
    0.63 ± 0.11
    No statistical analyses for this end point

    Secondary: Change From Baseline in Right Ventricular End Diastolic Volume (RVEDV) to Week 26

    Close Top of page
    End point title
    Change From Baseline in Right Ventricular End Diastolic Volume (RVEDV) to Week 26
    End point description
    Change from baseline to Week 26 in RVEDV assessed by cardiac MRI was reported. Safety set included all screened subjects who received at least one dose of study drug. Here ‘N’ (number of subjects analyzed) signifies the number of subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 26
    End point values
    Macitentan 10 mg
    Number of subjects analysed
    78
    Units: mL
        least squares mean (confidence interval 95%)
    -6.22 (-12.50 to 0.07)
    No statistical analyses for this end point

    Secondary: Change From Baseline in Right Ventricular End Systolic Volume (RVESV) to Week 26

    Close Top of page
    End point title
    Change From Baseline in Right Ventricular End Systolic Volume (RVESV) to Week 26
    End point description
    Change from baseline to Week 26 in RVESV assessed by cardiac MRI was reported. Safety set included all screened subjects who received at least one dose of study drug. Here ‘N’ (number of subjects analyzed) signifies the number of subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 26
    End point values
    Macitentan 10 mg
    Number of subjects analysed
    78
    Units: mL
        least squares mean (confidence interval 95%)
    -16.39 (-20.56 to -12.21)
    No statistical analyses for this end point

    Secondary: Change From Baseline in Right Ventricular Ejection Fraction (RVEF) to Week 26 (% Blood Volume)

    Close Top of page
    End point title
    Change From Baseline in Right Ventricular Ejection Fraction (RVEF) to Week 26 (% Blood Volume)
    End point description
    Change from baseline to Week 26 in RVEF based on pulmonary artery flow assessed by cardiac MRI was reported. Safety set included all screened subjects who received at least one dose of study drug. Here ‘N’ (number of subjects analyzed) signifies the number of subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 26
    End point values
    Macitentan 10 mg
    Number of subjects analysed
    72
    Units: Percentage of blood volume
        least squares mean (confidence interval 95%)
    10.14 (7.46 to 12.83)
    No statistical analyses for this end point

    Secondary: Change From Baseline in Right Ventricle (RV) Mass to Week 26

    Close Top of page
    End point title
    Change From Baseline in Right Ventricle (RV) Mass to Week 26
    End point description
    Change from baseline to Week 26 in RV mass assessed by cardiac MRI was reported. Safety set included all screened subjects who received at least one dose of study drug. Here ‘N’ (number of subjects analyzed) signifies the number of subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 26
    End point values
    Macitentan 10 mg
    Number of subjects analysed
    78
    Units: Gram
        least squares mean (confidence interval 95%)
    -10.10 (-13.81 to -6.39)
    No statistical analyses for this end point

    Secondary: Change From Baseline in Six Minutes Walk Distance (6MWD) to Week 26

    Close Top of page
    End point title
    Change From Baseline in Six Minutes Walk Distance (6MWD) to Week 26
    End point description
    6MWD is a non-encouraged test performed in a 30 meter (m) long flat corridor, where the subject is instructed to walk as far as possible, back and forth around two cones, with the permission to slow down, rest, or stop if needed. This test is used to assess exercise capacity. The test was performed about 30 minutes after study drug administration. Any increase in the walk distance was considered improvement from baseline. Safety Set included all screened subjects who received at least one dose of study drug. Here ‘N’ (number of subjects analyzed) signifies the number of subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 26
    End point values
    Macitentan 10 mg
    Number of subjects analysed
    83
    Units: Meters
        least squares mean (standard error)
    38.85 ± 7.37
    No statistical analyses for this end point

    Secondary: Change From Baseline in World Health Organization Functional Class (WHO FC) to Week 26

    Close Top of page
    End point title
    Change From Baseline in World Health Organization Functional Class (WHO FC) to Week 26
    End point description
    WHO FC is a classification which reflects disease severity based on symptoms. WHO Functional Classification of pulmonary hypertension comprises of Class I (subjects with pulmonary hypertension but without resulting limitation of physical activity), II (subjects with pulmonary hypertension resulting in slight limitation of physical activity), III (subjects with pulmonary hypertension resulting in marked limitation of physical activity) and IV (subjects with pulmonary hypertension with inability to carry out any physical activity without symptoms). Changes from baseline to Week 26 included: improvement (change from a higher to a lower FC), worsening (change from a lower to a higher FC) or unchanged/stable (same FC at baseline and at the post-baseline time point). Safety Set included all screened subjects who received at least one dose of study drug.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 26
    End point values
    Macitentan 10 mg
    Number of subjects analysed
    87
    Units: Subjects
    number (not applicable)
        Missing WHO FC
    5
        Worsened WHO FC
    1
        Unchanged WHO FC
    35
        Improved WHO FC
    46
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Up to 420 Days
    Adverse event reporting additional description
    Safety Set included all screened subjects who received at least one dose of study drug.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    22.0
    Reporting groups
    Reporting group title
    Macitentan 10 mg
    Reporting group description
    Subjects received macitentan 10 milligrams (mg) tablets once daily until the premature discontinuation of study drug or end of treatment (EOT) on the day of the last dose of study drug at Week 52.

    Serious adverse events
    Macitentan 10 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    15 / 87 (17.24%)
         number of deaths (all causes)
    1
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Pancreatic Carcinoma
         subjects affected / exposed
    1 / 87 (1.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    1 / 87 (1.15%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    General disorders and administration site conditions
    Therapeutic Response Decreased
         subjects affected / exposed
    1 / 87 (1.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Reproductive system and breast disorders
    Dysfunctional Uterine Bleeding
         subjects affected / exposed
    1 / 87 (1.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Dysmenorrhoea
         subjects affected / exposed
    1 / 87 (1.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Menorrhagia
         subjects affected / exposed
    1 / 87 (1.15%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Pelvic Haemorrhage
         subjects affected / exposed
    1 / 87 (1.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiac disorders
    Acute Myocardial Infarction
         subjects affected / exposed
    2 / 87 (2.30%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Angina Pectoris
         subjects affected / exposed
    1 / 87 (1.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Atrial Fibrillation
         subjects affected / exposed
    1 / 87 (1.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiac Arrest
         subjects affected / exposed
    1 / 87 (1.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Right Ventricular Failure
         subjects affected / exposed
    1 / 87 (1.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Coronary Artery Disease
         subjects affected / exposed
    1 / 87 (1.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Ventricular Hypokinesia
         subjects affected / exposed
    1 / 87 (1.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 87 (1.15%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Haemolytic Anaemia
         subjects affected / exposed
    1 / 87 (1.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Iron Deficiency Anaemia
         subjects affected / exposed
    1 / 87 (1.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Epistaxis
         subjects affected / exposed
    1 / 87 (1.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Dyspnoea
         subjects affected / exposed
    1 / 87 (1.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pulmonary Arterial Hypertension
         subjects affected / exposed
    2 / 87 (2.30%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Pulmonary Embolism
         subjects affected / exposed
    2 / 87 (2.30%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Nervous system disorders
    Syncope
         subjects affected / exposed
    1 / 87 (1.15%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Rectal Haemorrhage
         subjects affected / exposed
    1 / 87 (1.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Renal and urinary disorders
    Acute Kidney Injury
         subjects affected / exposed
    1 / 87 (1.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal and connective tissue disorders
    Rheumatoid Arthritis
         subjects affected / exposed
    1 / 87 (1.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Systemic Lupus Erythematosus
         subjects affected / exposed
    1 / 87 (1.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Metabolism and nutrition disorders
    Hypoglycaemia
         subjects affected / exposed
    1 / 87 (1.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Cholangitis Infective
         subjects affected / exposed
    1 / 87 (1.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Escherichia Bacteraemia
         subjects affected / exposed
    1 / 87 (1.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cytomegalovirus Infection
         subjects affected / exposed
    1 / 87 (1.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Herpes Zoster
         subjects affected / exposed
    1 / 87 (1.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumonia
         subjects affected / exposed
    3 / 87 (3.45%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Urinary Tract Infection
         subjects affected / exposed
    1 / 87 (1.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Sepsis
         subjects affected / exposed
    2 / 87 (2.30%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Macitentan 10 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    57 / 87 (65.52%)
    Vascular disorders
    Flushing
         subjects affected / exposed
    5 / 87 (5.75%)
         occurrences all number
    5
    Investigations
    Haemoglobin Decreased
         subjects affected / exposed
    10 / 87 (11.49%)
         occurrences all number
    11
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    10 / 87 (11.49%)
         occurrences all number
    10
    Nasal Congestion
         subjects affected / exposed
    8 / 87 (9.20%)
         occurrences all number
    8
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    12 / 87 (13.79%)
         occurrences all number
    13
    Headache
         subjects affected / exposed
    18 / 87 (20.69%)
         occurrences all number
    19
    General disorders and administration site conditions
    Oedema Peripheral
         subjects affected / exposed
    19 / 87 (21.84%)
         occurrences all number
    19
    Pyrexia
         subjects affected / exposed
    7 / 87 (8.05%)
         occurrences all number
    9
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    6 / 87 (6.90%)
         occurrences all number
    7
    Diarrhoea
         subjects affected / exposed
    8 / 87 (9.20%)
         occurrences all number
    9
    Musculoskeletal and connective tissue disorders
    Back Pain
         subjects affected / exposed
    7 / 87 (8.05%)
         occurrences all number
    7
    Myalgia
         subjects affected / exposed
    9 / 87 (10.34%)
         occurrences all number
    11
    Pain in Extremity
         subjects affected / exposed
    6 / 87 (6.90%)
         occurrences all number
    7
    Infections and infestations
    Upper Respiratory Tract Infection
         subjects affected / exposed
    10 / 87 (11.49%)
         occurrences all number
    17
    Nasopharyngitis
         subjects affected / exposed
    6 / 87 (6.90%)
         occurrences all number
    7

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    17 Feb 2015
    This amendment included the following changes: initial combination therapy with macitentan and a PDE-5 inhibitor was allowed in treatment-naive participants; pressure-volume endpoints were to be analyzed as exploratory endpoints instead of secondary endpoints; MRI variables were removed from the metabolism substudy.
    13 Aug 2015
    This amendment included the following changes: RHC data obtained at the study site before informed consent signature were accepted if RHC was performed between Day −28 and Day 1; spirometry eligibility criteria were simplified.
    30 May 2016
    This amendment included the following changes: eligibility criteria were modified to include participants with PAH associated with connective tissue disease, elderly participants up to 74 years of age, and subjects with a cMRI-compatible pacemaker; the window to perform cMRI and RHC within 7 days of each other was extended to 21 days.
    08 Nov 2016
    This amendment included the following change: an interim analysis for efficacy was added to the protocol to allow for study termination if both primary endpoints were met early.

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, visit the EMA Service Desk , log in using your EMA account and open a ticket specifying "EU CTR" in your request.
    If you do not have an account, please visit the EMA Account management page page click on "Create an EMA account" and follow the instructions.
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2022 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA