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    The EU Clinical Trials Register currently displays   42517   clinical trials with a EudraCT protocol, of which   7000   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2004-004061-15
    Sponsor's Protocol Code Number:SPD422-403
    National Competent Authority:Bulgarian Drug Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2007-03-20
    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 ConcernedBulgarian Drug Agency
    A.2EudraCT number2004-004061-15
    A.3Full title of the trial
    A Phase IIIb, randomised, open label study to compare the safety, efficacy and tolerability of anagrelide hydrochloride versus hydroxyurea in high-risk essential thrombocythaemia patients.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to compare the safety and effectiveness of anagrelide and hydroxyurea in high-risk essential thrombocythaemia patients.
    A.3.2Name or abbreviated title of the trial where available
    COMET
    A.4.1Sponsor's protocol code numberSPD422-403
    A.5.4Other Identifiers
    Name:CT2004-004-061-15Number:Not available
    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 SponsorShire Pharmaceutical Development Ltd.
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportShire Pharmaceuticals
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationNot available
    B.5.2Functional name of contact pointNot available
    B.5.3 Address:
    B.5.3.1Street AddressNot available
    B.5.3.2Town/ cityNot available
    B.5.3.3Post codeNot available
    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 Xagrid
    D.2.1.1.2Name of the Marketing Authorisation holderShire Pharmaceutical Contracts 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/3/00/010
    D.3 Description of the IMP
    D.3.1Product nameXagrid
    D.3.4Pharmaceutical form Capsule, hard
    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 INNAnagrelide hydrochloride
    D.3.9.1CAS number 58579-51-4
    D.3.9.2Current sponsor codeSPD-422-404
    D.3.9.3Other descriptive nameCOMET
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number0.5
    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 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 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 No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Hydrea
    D.2.1.1.2Name of the Marketing Authorisation holderBristol-Myers Squibb
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameHydrea
    D.3.4Pharmaceutical form Capsule, hard
    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 INNHydroxycarbamide
    D.3.9.1CAS number 127-07-1
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number500
    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
    Essential thrombocythaemia
    E.1.1.1Medical condition in easily understood language
    ET is a disorder of the bone marrow, which causes too many platelets to be produced. There is a risk of problems such as blood clots forming unnecessarily and excessive bleeding.
    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 14.0
    E.1.2Level PT
    E.1.2Classification code 10015493
    E.1.2Term Essential thrombocythaemia
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To compare the safety of anagrelide and hydroxyurea in short and long term usage of up to three years with particular reference to cardiovascular safety (as assessed by echocardiogram).
    E.2.2Secondary objectives of the trial
    To compare the efficacy of angrelide and hydroxyurea in terms of platelet count after 6 months of treatment.

    To compare the efficacy of anagrelide and hydroxyurea in terms of platelet count after 3 months of treatment.

    To compare the efficacy of anagrelide and hydroxyurea in terms of the number of patients achieving a complete response.

    To compare the cytoreductive impact of anagrelide and hydroxyurea on white blood cell and red blood cell lines.

    To investigate the tolerability of anagrelide and hydroxyurea in short term and long term usage of up to three years.

    To investigate the effects of anagrelide and hydroxyurea on incidence of disease related thrombotic and haemorrhagic events.

    To compare the average time to response following treatment with anagrelide or hydroxyurea.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Patients must have given written informed consent to participate in the study.
    Patients must be aged ≥ 18 years.
    Previously untreated with a cytotreductive agent.
    Confirmed diagnosis of ET - High Risk Profile.
    Satisfactory Medical assessment with no clinically significant and relevant abnormalities.
    If patients are female and of childbearing potential they must have a negative serum pregnancy test prior to entering the study and must agree to use effective birth control for the duration of the study. Pregnant or lactating women are excluded from participation.
    Patients must be able, willing and likely to comply with the study procedures and restrictions.
    E.4Principal exclusion criteria
    Patients with a diagnosis of any other myeloproliferative disorder (MPD).
    Any known cause for a secondary thrombocytosis.
    Previous or current treatment with cytoreductive therapy.
    Anticoagulant therapies.
    Anti-aggregant therapies, including aspirin. (Aspirin or other anti-aggregant therapy is allowed up to the point of randomisation).
    Known or suspected intolerance to study materials.
    Known or suspected Heart Disease.
    Left Ventricular Ejection Fraction (LVEF) <55%.
    Treatment with any medications known to alter ventricular ejection fraction.
    Life threatening malignancy or neoplasia which in the opinion of the investigator is unrelated to thrombocythaemia.
    Severe renal impairment defined as creatinine clearance <30ml/min, or severe hepatic impairment defined as elevated transaminases >5xULN.
    Clinically significant abnormal laboratory values (excluding markers of essential thrombocythaemia) will exclude the patient from the study as will known infection with hepatitis B, hepatitis C or HIV.
    Patients with a history of drug/alcohol abuse (within the previous 2 years).
    Patients must not have participated in another investigational study within 30 days prior to enrolment or for a longer duration if specified in local regulations.
    E.5 End points
    E.5.1Primary end point(s)
    The primary outcome for this study is the safety measurement LVEF. LVEF will be measured at predefined intervals (pre-treatment and Months 1,2,3,6,9,12,18,24,30 and 36) during the study and the response (slope) in LVEF for each patients will be obtained using linear regression. LVEF will be modelled as a linear function of time with a separate slope and intercept for each patient.

    The mean slope for each treatment group, the difference in the mean slopes between the two treatment groups, and the associated two-sided 95% confidence intervals will be presented. If the 95% CI for difference lies entirely below 2%/year then it will be concluded that the effect of anagrelide on LVEF is no worse than that observed for hydroxyurea.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Safety with particular reference to cardiovascular safety of anagrelide and hydroxyurea will be performed in short and long term usage of up to 3 years
    E.5.2Secondary end point(s)
    -Mean platelet count at 3 months.
    - Mean and percentage platelet count reduction from baseline at 3 and 6 months
    - The proportion of patients achieving a complete or partial response will be summarised by treatment group
    - The median time to response will be summarised using Kaplan-Meier methodology.The minimum and maximum time to response along with a 95% CI will also be
    presented.
    - Incidence of disease related thrombotic and haemorrhagic events will be summarised by treatment group at baseline and post-baseline.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Mean platelet count at 3 months.
    - Mean and percentage platelet count reduction from baseline at 3 and 6 months
    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 No
    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 Yes
    E.6.13.1Other scope of the trial description
    Tolerability
    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 Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    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) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.3.1Comparator description
    Hydroxyurea
    E.8.2.4Number of treatment arms in the trial2
    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 concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA50
    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
    Last visit of the last subject
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years7
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years7
    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.1.3Elderly (>=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 state25
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 154
    F.4.2.2In the whole clinical trial 184
    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 Decision2008-03-13
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2008-03-25
    P. End of Trial
    P.End of Trial StatusCompleted
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