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    The EU Clinical Trials Register currently displays   42732   clinical trials with a EudraCT protocol, of which   7035   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2008-006785-29
    Sponsor's Protocol Code Number:AC-054-302
    National Competent Authority:Finland - Fimea
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2009-04-03
    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 ConcernedFinland - Fimea
    A.2EudraCT number2008-006785-29
    A.3Full title of the trial
    A prospective, multi-center, double-blind, randomized, placebo-controlled, parallel-group study to assess the efficacy and safety of clazosentan in reducing vasospasm-related morbidity and all-cause mortality in adult patients with aneurysmal subarachnoid hemorrhage treated by endovascular coiling.
    A.3.2Name or abbreviated title of the trial where available
    CONSCIOUS 3
    A.4.1Sponsor's protocol code numberAC-054-302
    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 SponsorActelion Pharmaceuticals Ltd.
    B.1.3.4CountrySwitzerland
    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 Yes
    D.2.5.1Orphan drug designation numberEU/3/03/182
    D.3 Description of the IMP
    D.3.1Product nameClazosentan
    D.3.2Product code ACT-108475 or AXV-034343
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNClazosentan
    D.3.9.1CAS number 180384-56-9
    D.3.9.2Current sponsor codeACT-108475
    D.3.9.3Other descriptive nameAXV-034343
    D.3.10 Strength
    D.3.10.1Concentration unit mg/h milligram(s)/hour
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number to 5
    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.IMP: 2
    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 Yes
    D.2.5.1Orphan drug designation numberEU/3/03/182
    D.3 Description of the IMP
    D.3.1Product nameClazosentan
    D.3.2Product code ACT-108475 or AXV-034343
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNClazosentan
    D.3.9.1CAS number 180384-56-9
    D.3.9.2Current sponsor codeACT-108475
    D.3.9.3Other descriptive nameAXV-034343
    D.3.10 Strength
    D.3.10.1Concentration unit mg/h milligram(s)/hour
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number to 15
    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 placeboIntravenous infusion
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Indication: Subarachnoid aneurysmal hemorrhage
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 11
    E.1.2Level LLT
    E.1.2Classification code 10042316
    E.1.2Term <Manually entered code. Term in E.1.1>
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    •To demonstrate that at least one dose (5 or 15 mg/h) of clazosentan reduces the incidence of cerebral vasospasm related morbidity and all-cause mortality within 6 weeks post aneurysmal subarachnoid hemorrhage (aSAH) in patients treated by endovascular coiling.
    E.2.2Secondary objectives of the trial
    •To demonstrate that at least one dose (5 or 15 mg/h) of clazosentan improves clinical outcome at Week 12 post-aSAH in patients treated by endovascular coiling, as measured by the dichotomized Glasgow Outcome Scale (extended version(GOSE)).
    •To evaluate the impact of clazosentan on total infarct volume at Week 6 post-aSAH in patients treated by endovascular coiling, and on each individual component of the primary endpoint.
    •To evaluate the safety and tolerability of clazosentan.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1.Males and females aged 18 to 75 years (inclusive).
    2.Patients with a ruptured saccular aneurysm, confirmed by angiography (digital subtraction angiography [DSA] or computed tomography angiography [CTA], investigator’s assessment), and which has been successfully* secured by endovascular coiling. The time of aneurysm rupture must be known or possible to estimate with a reasonable degree of certainty.
    3.World Federation of Neurological Surgeons (WFNS) grade I–IV measured prior to the endovascular coiling procedure, and which does not worsen to grade V post-procedure (based on regular Glasgow Coma Scale [GCS])†
    4.Patients with any thick clot (short axis >= 4 mm) on baseline CT scan (investigator’s assessment).
    5.Women of childbearing potential must have a negative serum pregnancy test and must use a reliable method of contraception during the 12 weeks following study drug discontinuation.
    6.Written informed consent to participate in the study must be obtained from the patient or a legal representative prior to initiation of any study-mandated procedure and randomization.

    * A successful procedure is defined as a procedure after which the end of procedure DSA indicates that the coiling was complete or adequate (i.e., more than 50% of the volume of the aneurysm is filled in by coiling material, investigator's assessment) and when the patient is not scheduled for a 2nd procedure on the ruptured aneurysm within 12 weeks post-aSAH.

    †Patients must be evaluable for WFNS grade prior to the endovascular coiling procedure. Patients who cannot be assessed for WFNS post procedure due to a requirement for uninterrupted sedation (e.g., for high or unstable intracranial pressure [ICP]) may be included in the study provided that a CT scan is performed at least 12 hours post-procedure, but prior to randomization, ruling out any large procedure-related infarct.
    E.4Principal exclusion criteria
    1.Patients with subarachnoid hemorrhage (SAH) due to causes other than a saccular aneurysm (e.g., trauma or rupture of fusiform or mycotic aneurysms).
    2.Patients with giant aneurysms (height or width >= 25 mm).
    3.Patients with intraventricular or intracerebral blood, in the absence of subarachnoid blood, or with only a thin clot (short axis < 4 mm).
    4.Presence of cerebral vasospasm seen on angiography (investigator’s assessment) prior to the endovascular coiling procedure. (Intraprocedural cerebral vasospasm is not an exclusion criterion).
    5.Patients who experienced a major complication during the endovascular coiling procedure, such as massive intracranial bleeding, intracranial thromboembolism, coil migration, aneurysm perforation or rupture, arterial dissection, major arterial occlusion, a large territorial cerebral infarct defined as involving > 1/3 of a vascular territory, or a new major neurological deficit post-procedure (e.g., hemiplegia or aphasia lasting >= 12 hours post-aneurysm coiling).*
    6.Patients who have had their current ruptured aneurysm previously secured (successfully or not) by clipping.
    7.Patients coiled with coiling material, which has not been approved by local health authorities.
    8.Use of liquid embolism aneurysmal treatment or flow diverting device.
    9.Patients with several aneurysms among which the ruptured one cannot be identified with certainty and which are not all secured during the coiling procedure.
    10.Patients with no DSA at end-of-procedure.
    11.Patients planned to have another securing procedure for any aneurysm after randomization and prior Week 12 post-aSAH.
    12.Patients for whom study drug cannot be started within 56 hours after the aneurysm rupture.
    13.Patients for whom it is known, at the time of screening, that certain follow-up, or protocol-mandated imaging assessments will not be feasible.
    14.Patients with hypotension (systolic blood pressure (SBP) <= 90 mmHg) that is refractory to treatment.
    15.Patients with aspiration pneumonia.
    16.Patients with pulmonary edema or severe cardiac failure requiring inotropic support at the time of randomization.
    17.Any severe or unstable concomitant condition or disease (e.g., known significant neurological deficit, cancer, hematological, or coronary disease), or chronic condition (e.g., psychiatric disorder), which, in the opinion of the investigator, would affect the assessment of the safety or efficacy of the study drug.
    18.Significant kidney disease, as defined by plasma creatinine ≥ 2.5 mg/dL (221 ╬╝mol/l)
    and/or liver disease, as defined by total bilirubin > 2-fold the Upper Limit of Normal
    (ULN) as measured at the local laboratory, and/or known diagnosis or clinical
    suspicion of liver cirrhosis.
    19.Patients receiving i.v. nimodipine or i.v. nicardipine must have these drugs discontinued at least 4 hours prior to initiation of the study treatment.
    20.Patients who have received i.v. fasudil within the 24-hour period immediately preceding the planned start of study drug initiation.
    21.Patients starting statins less than 2 weeks prior to admission must have them discontinued prior to study drug initiation.
    22.Patients receiving cyclosporin A or other calcineurin inhibitors (e.g., tacrolimus), or patients for whom it is known at the time of randomization that these medications will be started during the study drug infusion period.
    23.Patients who have received an investigational product including investigational coil material within 28 days prior to randomization or those who have already participated in the current study or in the CONSCIOUS-2 study (AC-054-301).
    24.Patients unlikely to comply with the protocol (e.g., unable to return for follow-up visits).
    25.Known hypersensitivity to other endothelin receptor antagonists.
    26.Patients with current alcohol or drug abuse or dependence.

    * Further details on exclusion criterion number 5:
    “Large territorial infarct” refers to those infarcts detected during the endovascular coiling procedure or immediately post-procedure (i.e., CT performed for suspicion of cerebral infarct or other complication). This does not imply having to wait 24–48 hours post-procedure to perform the protocol-mandated CT scan in order to randomize a patient.


    Evaluation for a new major neurological deficit post-procedure implies the reversal of sedation (or waiting for the patient to recover from sedation) and the performance of a GCS examination (verbal scores in intubated patients may be extrapolated from the eye-opening and motor scores using the values provided in the table included in Section 3.9.1.2.1 of the protocol). In the event of a new major neurological deficit that does not improve within 12 hours after the endovascular coiling procedure, the patient cannot be included in the study.
    E.5 End points
    E.5.1Primary end point(s)
    The occurrence of cerebral vasospasm-related morbidity, and mortality of all causes within 6 weeks post-aSAH, defined by at least one of the following:
    1.Death (all causes)
    2.New cerebral infarct(s) due to cerebral vasospasm as either the primary or relevant contributing cause, or not adjudicated to be entirely due to causes other than vasospasm (e.g., lesions arising from intra-cerebral hemorrhage, the aneurysm endovascular coiling procedure, the primary injury, or ventricular drain encephalomalacia)*

    3.Delayed ischemic neurological deficit (DIND) due to cerebral vasospasm as either the primary or relevant contributing cause, or not adjudicated to be entirely due to causes other than vasospasm (e.g., hydrocephalus, seizure, etc.)*


    4.Administration of a valid rescue therapy in the presence of confirmed cerebral vasospasm on angiography (DSA or CTA)* (see detailed definition of this endpoint component and the list of qualifying rescue therapies in the study protocol, Section 3.8.1.1).

    *An independent Critical Events Committee (CEC) will adjudicate whether or not patients meet the primary endpoint and its individual morbidity components.

    It is expected that the incidence of vasospasm-related morbidity, and mortality of all causes, within 6 weeks post-aSAH is 35% in the placebo group. The treatment effect to be detected is a relative risk reduction of 30% (i.e., from 35% to 24.5%) in at least one dose group.
    As the baseline WFNS grade has a predictive value for the occurrence of the morbidity/mortality endpoint, an adjustment for this variable is made in the primary analysis.
    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 Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic Yes
    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 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 No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA66
    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 Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    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
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    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 years2
    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 Information not present in EudraCT
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Information not present in EudraCT
    F.1.1.3Newborns (0-27 days) Information not present in EudraCT
    F.1.1.4Infants and toddlers (28 days-23 months) Information not present in EudraCT
    F.1.1.5Children (2-11years) Information not present in EudraCT
    F.1.1.6Adolescents (12-17 years) Information not present in EudraCT
    F.1.2Adults (18-64 years) Yes
    F.1.3Elderly (>=65 years) Yes
    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 Information not present in EudraCT
    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 Yes
    F.3.3.6Subjects incapable of giving consent personally Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Patients who are unconscious or otherwise unable to give their own informed consent may participate, providing a surrogate informed consent has been obtained, as allowed in the local legislation
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state45
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 1297
    F.4.2.2In the whole clinical trial 1470
    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 Decision2009-06-03
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2009-05-20
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
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