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   39188   clinical trials with a EudraCT protocol, of which   6421   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).
     
    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:2008-005887-14
    Sponsor's Protocol Code Number:B1321003
    National Competent Authority:Slovakia - SIDC (Slovak)
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2009-02-20
    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 ConcernedSlovakia - SIDC (Slovak)
    A.2EudraCT number2008-005887-14
    A.3Full title of the trial
    A PHASE 3, MULTI-CENTER, RANDOMIZED, DOUBLE-BLIND, EFFICACY AND SAFETY STUDY OF MONOTHERAPY SITAXSENTAN SODIUM VERSUS COMBINATION THERAPY WITH SITAXSENTAN SODIUM AND SILDENAFIL CITRATE IN SUBJECTS WITH PULMONARY ARTERIAL HYPERTENSION WHO HAVE COMPLETED STUDY B1321001
    A.4.1Sponsor's protocol code numberB1321003
    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 SponsorPfizer Limited, Ramsgate Road, Sandwich, Kent, UK
    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 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 Yes
    D.2.1.1.1Trade name Thelin
    D.2.1.1.2Name of the Marketing Authorisation holderEncysive (UK) Limited
    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/3/04/234
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    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 INNSitaxsentan Sodium
    D.3.9.1CAS number 210421-64-0
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    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 Information not present in EudraCT
    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 Yes
    D.2.1.1.1Trade name Revatio
    D.2.1.1.2Name of the Marketing Authorisation holderPfizer Limited
    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/3/03/178
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    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 INNSildenafil Citrate
    D.3.9.1CAS number 139755-83-2
    D.3.9.2Current sponsor codeUK-92,480
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    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 Information not present in EudraCT
    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 placeboTablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Pulmonary Arterial Hypertension
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10064911
    E.1.2Term Pulmonary arterial hypertension
    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 of this study is to evaluate the efficacy of sitaxsentan (100 mg once daily) plus sildenafil (20 mg TID) as compared to sitaxsentan monotherapy by determining time to clinical worsening in the treatment of subjects with PAH who have completed study B1321001.
    E.2.2Secondary objectives of the trial
    The secondary objectives of this study are to evaluate the safety and efficacy of sitaxsentan (100 mg once daily) plus sildenafil (20 mg TID) as compared to sitaxsentan monotherapy in the treatment of subjects with PAH who have completed study B1321001 by determining change from Baseline/Day 1 to Weeks 12, 24, and 48 in 6MWD, WHO functional class, and SF-36 Health Survey.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Previously enrolled in B1321001 and completed the 12-week study as planned.
    2. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study.
    3. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
    4. Has a current diagnosis of symptomatic PAH classified by one of the following:
    a. Idiopathic, primary or familial pulmonary arterial hypertension (IPAH, PPH, or FPAH)
    b. PAH associated with one of the following connective tissue diseases:
    i. Systemic sclerosis (scleroderma)
    ii. Limited scleroderma
    iii. Mixed connective tissue disease
    iv. Systemic lupus erythematosus
    v. Overlap syndrome
    c. Exposure to drugs and toxins (e.g., anorexigens, L-tryptophan, toxic rapeseed oil)
    5. Has World Health Organization (WHO) functional class III symptoms at the time of the first screening day for B1321001.
    6. Is ≥16 and ≤80 years of age (at the time of the first screening day for B1321001).
    7. Has a body weight of ≥40 kg at the time of the first screening day for B1321001.
    8. Had 6-minute walk distances ≥150 and ≤450 meters and distances walked within 15% of one another on two consecutive tests at the time of B1321001 screening.
    9. Had a ventilation-perfusion (V/Q) lung scan, spiral/helical/electron beam computed tomography (CT), or pulmonary angiogram within 3 years prior to the time of the first screening day for B1321001 that shows no evidence of thromboembolic disease (normal or low probability for pulmonary embolism). If a V/Q scan is abnormal (not normal or low probability), then a confirmatory CT, angiography or selective pulmonary angiography must exclude chronic thromboembolic disease.
    10. Had the diagnosis of PAH confirmed by a cardiac catheterization within 6 months prior to the time of the first screening day for B1321001 with the following values:
    a. Mean pulmonary artery pressure (mPAP) >25 mmHg (at rest)
    b. Pulmonary capillary wedge pressure (PCWP) or left ventricular-end diastolic pressure ≤15 mm Hg; and
    c. Pulmonary vascular resistance (PVR) >3 mm Hg/L/min or 240 dynes*sec/cm5
    11. If on vasodilators, digoxin, diuretics, spironolactone, or oxygen was receiving a stable dose for at least 1 month prior to the time of the first screening day for B1321001.
    12. If on corticosteroids, was receiving a stable dose of ≤20 mg/day of prednisone (or equivalent dose, if other corticosteroid) for at least 1 month prior to the time of the first screening day for B1321001.
    13. If on warfarin (Coumadin®) or other vitamin K antagonists, was receiving stable treatment for at least 1 month prior to the time of first screening day for B1321001; titration to target international normalized ratio (INR) is permitted.
    14. If on calcium channel blockers, was receiving a stable dose for at least 1 month prior to the time of first screening day for B1321001 and was maintained throughout the study.
    15. If on any medication belonging to the statin drug class (eg, lovastatin, atorvastatin), was receiving a stable dose for at least 3 months prior to the time of first screening day for B1321001 and was maintained throughout the study.
    16. Women of childbearing potential must be using 2 forms of medically acceptable contraception (at least 1 barrier method), have a negative pregnancy test at Baseline/Day 1 and agree to use reliable methods of contraception for at least 1 month after the final study visit. Women who are surgically sterile or those who are post-menopausal for at least 2 years are not considered to be of childbearing potential.
    E.4Principal exclusion criteria
    1. Treated with an investigational drug, other than sitaxsentan sodium in B1321001, or device that has not received regulatory approval within the 30 days prior to Baseline/Day 1 or during the study.
    2. Has a known allergy to ingredients of Phosphodiesterase (PDE) inhibitor or Endothelin Receptor Antagonist (ETRA) drug classes or the tablet excipients.
    3. Is taking, or has an anticipated need for systemic administration (oral, intravenous (IV)) of cyclosporine A for the duration of the study.
    4. Is taking any specific cytochrome P450 3A4 (CYP3A4) inhibitors (eg, ketoconazole, itraconazole), protease inhibitors (eg, ritonavir, saquinavir), alpha blockers, nitrates or nitric oxide donors (eg, arginine supplement, nicorandil) in any form.
    5. Treatment for PAH with any of the following within 30 days prior to the time of first screening day for B1321001, during the B1321001 study, or an anticipated needed during the B1321003 study:
    a. Any chronic intravenous or subcutaneous prostacyclin or prostacyclin analogue
    b. Any alternative phosphodiesterase-5 (PDE-5) inhibitor
    c. Any alternative ETRA
    d. Intravenous inotropes; or
    e. Inhaled nitric oxide (excluding acute vasodilator testing during diagnostic cardiac catheterization)
    6. Is using chronic arginine supplementation including HeartBar®. This must have been stopped for at least 30 days prior to the time of first screening day for B1321001.
    7. Had pulmonary function tests within 3 months prior to the time of the first screening day for B1321001 that reveal evidence of significant parenchymal lung disease. Parenchymal lung disease is defined as:
    a. Total lung capacity (TLC) <70% (predicted)
    b. Forced expiratory volume in 1 second FEV1 ≤70% (predicted), or
    c. Forced expiratory volume in 1 second/forced vital capacity ratio (FEV1/FVC) ≤60%
    8. Has known human immunodeficiency virus (HIV) infection, under treatment with or has anticipated need for HIV specific antiretroviral therapy.
    9. Has history of left-sided heart disease and/or clinically significant cardiac disease, including but not limited to any of the following:
    a. Repaired or unrepaired congenital heart disease (CHD)
    b. Aortic or mitral valve disease (stenosis or regurgitation) defined as more than minimum aortic insufficiency and more than moderate mitral regurgitation
    c. Pericardial constriction
    d. Restrictive or congestive cardiomyopathy
    e. Left ventricular ejection fraction <40% by multiple gated acquisition scan (MUGA), angiography or echocardiography
    f. Left ventricular shortening fraction <22% by echocardiography
    g. Symptomatic coronary disease with demonstrable ischemia; or
    h. Evidence of left ventricular hypertrophy or diastolic dysfunction obtained by electrocardiogram or echocardiography within 3 months prior to the time of the first screening day for B1321001. Echocardiographic (ECHO) evidence of concentric remodeling and/or diastolic dysfunction is defined as 1 or more of the following within 3 months prior to the time of the first screening day for B1321001:
    i. Left ventricular mass ≥125 g/m2
    ii. Left atrial diameter ≥4.5 cm
    iii. Wall thickness of ≥11 mm
    iv. Relative wall thickness of 2 times wall thickness ÷ radius being ≥0.45 mm
    10. Has a history of portal hypertension or chronic liver disease, including hepatitis B and/or hepatitis C (with evidence of recent infection and/or active virus replication) defined as mild to severe hepatic impairment (Child-Pugh Class A-C).
    11. Has uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure >160 mm Hg or sitting diastolic blood pressure >100 mm Hg at Baseline.
    12. Has hypotension defined as systolic arterial pressure <90 mm Hg after sitting for 5 minutes at Baseline.
    13. Has hepatic dysfunction, defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >1.5 times the upper limit of the normal (ULN) range at Baseline.
    14. Experienced a Serious Adverse Event (SAE) categorized as a bleeding event while on B1321001.
    15. Has chronic renal insufficiency as defined by serum creatinine >2.5 mg/dL at screening for B1321001 study entry or requires dialytic support.
    16. Has a hemoglobin concentration <10 g/dL at Baseline/Day 1.
    17. History of obstructive sleep apnea (treated or untreated).
    18. History of atrial septostomy.
    19. Has known hereditary degenerative retinal disorders (such as retinitis pigmentosa) or history of non-arteritic anterior ischaemic optic neuropathy.
    20. Has untreated proliferative diabetic retinopathy.
    E.5 End points
    E.5.1Primary end point(s)
    The primary efficacy endpoint is time to clinical worsening. This will be assessed and will be evaluated as the number of days between the first dose of study drug and the occurrence of a predefined clinical worsening event. The following will be considered clinical worsening events with confirmation by a blinded Adjudication Committee:
    • Hospitalization for worsening PAH (defined as hospitalization for at least 24 hours occasioned by a clinical condition clearly related to PAH such as right heart failure, arrhythmia, syncope, for intravenous diuretic or inotropic medications such as dobutamine, or for initiation of other PAH disease specific therapies)
    • On-study death
    • Heart-lung or lung transplant
    • Atrial septostomy, or
    • Withdrawal due to the addition of any of the following chronic medications for the treatment of worsening PAH: prostacyclin, prostacyclin analogues, phosphodiesterase-5 inhibitors, alternative endothelin receptor antagonists, intravenous inotropes; or increase in dose of calcium channel blockers, oxygen
    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 Yes
    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 Information not present in EudraCT
    E.7.1.2Bioequivalence study Information not present in EudraCT
    E.7.1.3Other Information not present in EudraCT
    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 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 Yes
    E.8.2.3Other No
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.4.1Number of sites anticipated in Member State concerned1
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA10
    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 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
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    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 years3
    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 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 state3
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 30
    F.4.2.2In the whole clinical trial 150
    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 Decision2009-04-01
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2009-04-01
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2010-12-08
    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 © 1995-2021 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA