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    Summary
    EudraCT Number:2009-015247-16
    Sponsor's Protocol Code Number:162
    National Competent Authority:Czech Republic - SUKL
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2010-10-11
    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 ConcernedCzech Republic - SUKL
    A.2EudraCT number2009-015247-16
    A.3Full title of the trial
    A Randomized, Double-Blind, Active-Controlled, Multicenter Study of Patients with Primary Hypercholesterolemia and High Cardiovascular Risk Who Are Not Adequately Controlled with Atorvastatin 10 mg: A Comparison of the Efficacy and Safety of Switching to Coadministration Ezetimibe and Atorvastatin Versus Doubling the Dose of Atorvastatin or Switching to Rosuvastatin
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    The study is to evaluate the effectiveness and safety of switching to coadministration ezetimibe and atorvastatin compared with doubling the dose of atorvastatin or switching to rosuvastatin in patients with primary hypercholesterolemia and high cardiovascular risk who are not adequately controlled with atorvastatin 10 mg.

    Ezetimibe, atorvastatin and rosuvastatin are each available by prescription to treat high blood cholesterol levels.
    A.3.2Name or abbreviated title of the trial where available
    SWITCH
    A.4.1Sponsor's protocol code number162
    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 SponsorMerck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
    B.1.3.4CountryUnited States
    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 supportMerck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMerck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
    B.5.2Functional name of contact pointGlobal Clinical Trial Operations
    B.5.3 Address:
    B.5.3.1Street AddressK15-2310, 2000 Galloping Hill Road
    B.5.3.2Town/ cityKenilworth
    B.5.3.3Post codeNJ 07033
    B.5.3.4CountryUnited States
    B.5.4Telephone number+1 732 594 1218
    B.5.5Fax number+1 732 594 3690
    B.5.6E-mailcynthia.cuffie@merck.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name EZETROL 10 mg tablety
    D.2.1.1.2Name of the Marketing Authorisation holderMerck Sharp & Dohme B.V., Nizozemsko
    D.2.1.2Country which granted the Marketing AuthorisationCzech Republic
    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.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNEZETIMIBE
    D.3.9.1CAS number 163222-33-1
    D.3.9.2Current sponsor codeMK-0653
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    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.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 LIPITOR 10 mg
    D.2.1.1.2Name of the Marketing Authorisation holderPfizer Ireland Pharmaceuticals
    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.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 134523-03-8
    D.3.9.3Other descriptive nameATORVASTATIN CALCIUM
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    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.IMP: 3
    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 LIPITOR 20 mg
    D.2.1.1.2Name of the Marketing Authorisation holderPfizer Ireland Pharmaceuticals
    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.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 134523-03-8
    D.3.9.3Other descriptive nameATORVASTATIN CALCIUM
    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) 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.IMP: 4
    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 LIPITOR 40 mg
    D.2.1.1.2Name of the Marketing Authorisation holderPfizer Ireland Pharmaceuticals
    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.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 134523-03-8
    D.3.9.3Other descriptive nameATORVASTATIN CALCIUM
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number40
    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.IMP: 5
    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 CRESTOR 10 mg
    D.2.1.1.2Name of the Marketing Authorisation holderAstraZeneca UK Ltd
    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.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNROSUVASTATIN CALCIUM
    D.3.9.1CAS number 147098-20-2
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    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.IMP: 6
    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 CRESTOR 20 mg
    D.2.1.1.2Name of the Marketing Authorisation holderAstraZeneca UK Ltd
    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.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNROSUVASTATIN CALCIUM
    D.3.9.1CAS number 147098-20-2
    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) 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.IMP: 7
    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 SORTIS 10 mg
    D.2.1.1.2Name of the Marketing Authorisation holderPfizer Pharma GmbH, Berlin, Germany
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 134523-03-8
    D.3.9.3Other descriptive nameATORVASTATIN CALCIUM
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    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.IMP: 8
    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 SORTIS 20 mg
    D.2.1.1.2Name of the Marketing Authorisation holderPfizer Pharma GmbH, Berlin, Germany
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 134523-03-8
    D.3.9.3Other descriptive nameATORVASTATIN CALCIUM
    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) 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.IMP: 9
    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 SORTIS 40 mg
    D.2.1.1.2Name of the Marketing Authorisation holderPfizer Pharma GmbH, Berlin, Germany
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 134523-03-8
    D.3.9.3Other descriptive nameATORVASTATIN CALCIUM
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number40
    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
    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
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 3
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 4
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 5
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 6
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    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
    Primary Hypercholesterolemia
    E.1.1.1Medical condition in easily understood language
    Presence of high levels of cholesterol in the blood
    E.1.1.2Therapeutic area Body processes [G] - Metabolic Phenomena [G03]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level PT
    E.1.2Classification code 10020603
    E.1.2Term Hypercholesterolaemia
    E.1.2System Organ Class 10027433 - Metabolism and nutrition disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    In patients with primary hypercholesterolemia and high cardiovascular risk with LDL-C ≥100 mg/dL (2.59 mmol/L) and ≤160 mg/dL (4.14 mmol/L), to evaluate:

    1) at the end of Phase I, the additional LDL-C percentage reduction by switching to coadministered ezetimibe 10 mg + atorvastatin 10 mg compared to atorvastatin 20 mg among patients who are not adequately controlled with atorvastatin
    10 mg prior to randomization.

    2) at the end of Phase I, the additional LDL-C percentage reduction by switching to coadministered ezetimibe 10 mg + atorvastatin 10 mg compared to rosuvastatin
    10 mg among patients who are not adequately controlled with atorvastatin 10 mg prior to randomization.
    E.2.2Secondary objectives of the trial
    In patients with primary hypercholesterolemia and high cardiovascular risk with LDL-C ≥100 mg/dL (2.59 mmol/L) and ≤160 mg/dL (4.14 mmol/L), to evaluate:

    1) at the end of Phase II, the additional LDL-C percentage reduction by switching to coadministered ezetimibe 10 mg + atorvastatin 20 mg compared to atorvastatin 40 mg among patients who are not adequately controlled with atorvastatin
    10 mg prior to randomization and not adequately controlled with atorvastatin 20 mg during Phase I

    2) at the end of Phase II, the additional LDL-C percentage reduction by switching to coadministered ezetimibe 10 mg + atorvastatin 20 mg compared to rosuvastatin 20 mg among patients who are not adequately controlled with atorvastatin
    10 mg prior to randomization and who are not adequately controlled with rosuvastatin 10 mg during Phase I

    Please refer to protocol for the rest of the secondary objectives
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Men or women ≥18 and <80 years of age.

    2. Patient understands the study procedures, risks involved with the study, and voluntarily agrees to participate by giving written informed consent.

    3. Patient is at high cardiovascular risk (determined by a preliminary Cardiovascular Risk Assessment using historical lab values) and one of the following conditions are met:

    - Naïve to lipid-lowering therapy (or have been off such therapy for ≥6 weeks prior to Visit 1) and has a historical LDL-C value approximately within the range noted in the protocol*

    OR

    - Currently taking stable dose of a statin, ezetimibe, or statin + ezetimibe combination listed below with LDL-C lowering efficacy equivalent to or less than atorvastatin 10 mg and has a historical LDL-C value approximately within the range noted in the protocol.:*

    Simvastatin 10, 20 mg
    Pitavastatin 1 mg
    Atorvastatin 10 mg
    Pravastatin 10, 20, 40 mg
    Fluvastatin 20, 40, 80 mg
    Lovastatin 10, 20, 40 mg
    Ezetimibe 10 mg
    Ezetimibe 10 mg + Lovastatin 10 mg
    Ezetimibe 10 mg + Pravastatin 10 mg
    Ezetimibe 10 mg + Fluvastatin 20 mg

    4. Patient is willing to maintain an ESC / NCEP ATP III Therapeutic Lifestyle Changes(TLC) or similar cholesterol lowering diet for the duration of the study.

    5. A female patient who is of reproductive potential agrees to remain abstinent or use (or have their partner use) 2 acceptable methods of birth control for the duration of the study. Acceptable methods of birth control are: intrauterine device (IUD), diaphragm with spermicide, condom, vasectomy, and non-cyclical hormonal
    contraception.*

    6. Female patients who are receiving non-cyclical hormone therapy (including noncyclical hormone replacement therapy or any estrogen antagonist/agonist, or noncyclical oral contraceptives) if maintained on a stable dose and regimen for at least 8 weeks prior to Visit 1 and if willing to continue the same regimen throughout the study.

    Patients will be eligible to continue to Visit 3 (Week -1) if they meet the following criteria:

    7. Patient has a naïve or on-treatment LDL-C value within the range noted in the protocol at Visit 2 (sample collected at Visit 1).

    8. Patient has liver transaminases (ALT and AST) ≤2xULN (sample collected at Visit 1) with no active liver disease at Visit 2.

    9. Patient has creatine kinase (CK) levels ≤3xULN at Visit 2 (sample collected at Visit 1).

    10. Patient has triglyceride (TG) concentrations ≤350 mg/dL (3.95 mmol/L) at Visit 2 (sample collected at Visit 1).

    11. Patient meets 2004 NCEP ATP III / 2006 AHA ACC updated guidelines and 2007 Fourth Joint European Societies recommendations for high risk. Risk criteria are determined by the Framingham calculation (using lipid values obtained at Visit 1)*

    - High-risk patients without cardiovascular disease (CVD)* including patients who have (1) diabetes, or (2) multiple risk factors and a 10-year risk for CHD >20% (as determined by the Framingham calculation)

    - High-risk patients with cardiovascular disease (CVD)* including patients with established coronary and other atherosclerotic vascular disease

    Patients will be eligible to continue to Visit 5 (Week 5) if they meet the following criteria:

    12. Patient has completed the 5 week atorvastatin 10 mg run-in period.

    13. Patient has at least 75% compliance with run-in medication during the active run-in period (determined by pill count) or, if patients are <75% compliance with run-in medication, they will be permitted to continue if all other criteria are met and site personnel follow-up regularly via telephone to remind them to take study medication.

    14. LDL-C level ≥100 mg/dL (2.59 mmol/L) and ≤160 mg/dl (4.14 mmol/L) at Visit 4 (sample collected at Visit 3).

    15. Patient has triglyceride (TG) concentrations ≤400 mg/dL (4.52 mmol/L) at Visit 4 sample collected at Visit 3).

    Patients will be eligible to continue to Visit 7 (Week 11) if they meet the following criteria:

    16. Patient has completed the 6-week double blind treatment period.

    17. Notified by IVRS that patient is eligible to proceed directly to Visit 6 and will be part of the Phase II portion of the study based on treatment sequence determined at the randomization visit and/or meeting both blinded lipid criteria listed below:
    LDL-C level ≥100 mg/dL (2.59 mmol/L) and ≤160 mg/dl (4.14 mmol/L) at Visit 6 (sample collected at Visit 5). TG level ≤400 mg/dL (4.52 mmol/L) at Visit 6 (sample collected at Visit 5). *

    * See protocol for further details
    E.4Principal exclusion criteria
    1. Patient is Asian.

    2. Patient has hypersensitivity or intolerance to ezetimibe, atorvastatin, rosuvastatin, or any component of these medications, or has a history of significant myopathy or rhabdomyolysis with ezetimibe or any statin.

    3. Patient routinely consumes more than 2 alcoholic drinks per day (average >14 alcoholic drinks per week). *

    4. Female patient who is pregnant or lactating.

    5. Patient has been treated with any other investigational drug within 30 days of Visit 1 (Week -6).

    6. Patient has any condition or situation which, in the opinion of the investigator, might have posed a risk to the patient or interfere with participation in the study.

    Prohibited Medical Conditions
    7. Patient has congestive heart failure defined by NYHA (New York Heart Association) Class III or IV.

    8. Patient has had a myocardial infarction, coronary artery bypass surgery, angioplasty, or acute coronary syndrome within 3 months prior to Visit 1.

    9. Patient has uncontrolled cardiac arrhythmias or recent significant changes in the patient’s electrocardiogram (ECG) as taken within 6 months prior to Visit 1.

    10. Patient has homozygous familial hypercholesterolemia or has undergone LDL-C apheresis.

    11. Patient has had a partial ileal bypass, gastric bypass, or other significant intestinal malabsorption.

    12. Patient has uncontrolled hypertension (treated or untreated) with systolic blood pressure >160 mmHg or diastolic >100 mmHg at Visit 2 (Week –5). Investigators are encouraged to maximize blood pressure control according to current guidelines.

    13. Patient has estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 based on the 4-variable MDRD (Modification of Diet in Renal Disease) equation at Visit 1 (as done by the central lab), nephrotic syndrome or other clinically significant renal disease at Visit 1 (Week -6).

    14. Patient has uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins at Visit 1 (Week -6).*

    15. Patient has disorders of the hematologic, digestive, or central nervous systems including cerebrovascular disease (e.g. stroke, TIA) and degenerative disease that would limit study evaluation or participation.

    16. Patient has poorly controlled Type I or II diabetes mellitus (HbA1c ≥8.5% at Visit 1 or newly diagnosed (within 3 months of Visit 1) and/or patient has recent history of repeated hypoglycemia or unstable glycemic control, or has had a change in treatment of antidiabetic pharmacotherapy or change of ±10 units of insulin, within 2 months of Visit 1 (Week -6).*

    17. Patient who is known HIV positive.*

    18. Patient has a history of malignancy ≤5 years prior to signing informed consent, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.*

    19. Patient has a history of mental instability, drug/alcohol abuse within the past 5 years, or major psychiatric illness not adequately controlled and stable on pharmacotherapy.

    Prohibited Therapies

    20. Patient is currently taking medications that are potent inhibitors of cytochrome P-450 3A4 (CYP3A4), including systemic azole antifungals (e.g., fluconazole, ketoconazole); erythromycin, clarithromycin or cyclosporine

    21. Patient is currently taking other medications that may increase the risk of myopathy, including the combinations of protease inhibitors.*

    22. Patient consumes > 5 cups (1.2 L) of grapefruit juice per day.

    23. Patient has taken lipid-lowering agents including OTC supplements of fish oils containing >900 mg/day of EPA+DHA, red yeast extract, Cholestin, bile acid sequestrants, HMG-CoA reductase inhibitors or other cholesterol-lowering agents not listed below, ezetimibe/simvastatin and niacin (>200 mg/day) within 6 weeks prior to Visit 1 or fibrates within 8 weeks prior to Visit 1.*

    24. Patient is receiving treatment with systemic corticosteroids (intravenous, intramuscular and oral steroids). *

    25. Patient is currently treated with psyllium, other fiber-based laxatives, phytosterol margarines, and/or over the counter (OTC) therapies known to affect serum lipid levels, unless treated with a stable regimen for at least 6 weeks prior to Visit 1 (Week -6) and patient agrees to remain on constant regimen for the duration of the study.

    26. Patient has been on treatment with orlistat, sibutramine, or other anti-obesity medications and not maintained a stable dose within 1 month prior to study entry or is actively losing weight.

    27. Patient is taking any cyclical hormones (e.g., cyclical oral contraceptives, cyclical hormone replacement), including the combination of ethinyl estradiol and norethindrone, within 8 weeks prior to randomization [Visit 4 (Day 1)].

    28. Patient requires warfarin treatment and has not been on a stable dose with a stable International Normalized Ratio (INR) for at least 6 weeks prior to Visit 1(Week -6).

    * See protocol for further details
    E.5 End points
    E.5.1Primary end point(s)
    Percent change from baseline in LDL-C.
    E.5.1.1Timepoint(s) of evaluation of this end point
    The primary end point is the comparison of the change in LDL-C from baseline to the end of Phase I (Visit 6) after 6 weeks double-blinded treatment with EZ 10mg + Atorva 10 mg, compared to Atorva 20 mg, or Rosuva 10 mg.
    E.5.2Secondary end point(s)
    Secondary Endpoints:
    1) Additional percent change from baseline in LDL-C at the end of Phase II; comparison of EZ 10mg + Atorva 20 mg, to Atorva 40 mg, or Rosuva 20 mg
    2) Percent of patients reaching LDL-C <100 mg/dL (2.59 mmol/L) at the end of Phase I
    3) Percent of patients reaching LDL-C <100 mg/dL (2.59 mmol/L) at the end of Phase II.
    4) Percent changes from baseline in TC, TG, HDL-C, Apo B, Apo A-I, non-HDL-C, TC/HDL-C ratio, LDL-C/HDL-C ratio, Apo B/Apo A-I ratio, non-HDL-C/HDL-C ratio and hs-CRP at the end of Phase I.
    5) Additional percent changes from baseline in TC, TG, HDL-C, Apo B, Apo A-I, non-HDL-C, TC/HDL-C ratio, LDL-C/HDL-C ratio, Apo B/Apo A-I ratio, non-HDL-C/HDL-C ratio and hs-CRP at the end of Phase II.
    6) Safety and tolerability of EZ 10 mg + Atorva 10 mg versus Atorva 20 mg and Rosuva 10 mg and the safety of EZ 10 mg + Atorva 20 mg versus Atorva 40 mg and Rosuva 20 mg.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Secondary end points will be evaluated at the end of Phase I (Visit 6) following 6 weeks double-blinded treatment with either EZ 10mg + Atorva 10 mg, or Atorva 20 mg, or Rosouva 10 mg, and Phase II (Visit 8), following another 6 weeks double-blinded treatment with either EZ 10mg + Atorva 20 mg, or Atorva 40 mg, or Rosuva 20 mg.
    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 Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled 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 Yes
    E.8.1.7.1Other trial design description
    Multicenter
    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.8.2.4Number of treatment arms in the trial6
    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 concerned22
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA232
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Argentina
    Belgium
    Bulgaria
    Canada
    Chile
    Colombia
    Croatia
    Czech Republic
    Denmark
    Estonia
    Finland
    France
    Germany
    Hungary
    Israel
    Italy
    Lithuania
    Netherlands
    Norway
    Poland
    Portugal
    Romania
    Slovakia
    Slovenia
    Spain
    Sweden
    Turkey
    United Kingdom
    United States
    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
    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 years1
    E.8.9.1In the Member State concerned months11
    E.8.9.1In the Member State concerned days28
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months4
    E.8.9.2In all countries concerned by the trial days5
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 1131
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 377
    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 state120
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 990
    F.4.2.2In the whole clinical trial 1508
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Normal standard of care
    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 Decision2010-10-08
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2010-11-08
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2012-10-18
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