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   34922   clinical trials with a EudraCT protocol, of which   5688   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:2004-003934-32
    Sponsor's Protocol Code Number:ISIS 301012-CS3
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2005-01-19
    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 ConcernedGermany - BfArM
    A.2EudraCT number2004-003934-32
    A.3Full title of the trial
    A Phase II, Randomized, Double Blind, Placebo-Controlled Study to assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Varying Loading and Maintenance Dosing Regimens of ISIS 301012 Administered to Hypercholesterolemic Subjects.
    A.4.1Sponsor's protocol code numberISIS 301012-CS3
    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 SponsorIsis Pharmaceuticals 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 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 Information not present in EudraCT
    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.3.2Product code ISIS 301012
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 629167-92-6
    D.3.9.2Current sponsor codeISIS 301012
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200
    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 Information not present in EudraCT
    D.3.11.8Extractive medicinal product Information not present in EudraCT
    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 Yes
    D.3.11.13.1Other medicinal product typeAntisense Oligonucleotide
    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 Information not present in EudraCT
    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.3.2Product code ISIS 301012
    D.3.4Pharmaceutical form Powder for solution for injection
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 629167-92-6
    D.3.9.2Current sponsor codeISIS 301012
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100 per vial
    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 Information not present in EudraCT
    D.3.11.8Extractive medicinal product Information not present in EudraCT
    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 Yes
    D.3.11.13.1Other medicinal product typeAntisense Oligonucleotide
    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 placeboSolution for injection
    D.8.4Route of administration of the placeboSubcutaneous use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for injection
    D.8.4Route of administration of the placeboSubcutaneous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Hypercholesterolemia
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 7.0
    E.1.2Level LLT
    E.1.2Classification code 10020604
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To examine the safety and tolerability of varying load and maintenance dose/regimen of ISIS 301012 in hypercholesterolemic subjects
    E.2.2Secondary objectives of the trial
    To determine optimal load and maintenance dose/regimen for ISIS 301012 activity in hypercholesterolemic subjects.

    To characterize the pharmacokinetics and pharmacodynamics of ISIS 301012 during and following 3 months of treatment in hypercholesterolemic subjects
    E.2.3Trial contains a sub-study Information not present in EudraCT
    E.3Principal inclusion criteria
    1. Age 18 to 65 years
    2. Male or female gender.
    Females: Must be post-menopausal or surgically sterile (complete cessation of menstrual periods for at least one year prior to randomization, hysterectomy, bilateral oopherectomy, or tubal ligation > 6 months prior to randomization).
    Males: Must have been surgically sterilized by vasectomy, or is sexually abstinent, or using contraception with his partner from screening and throughout study participation. In addition, sexually active male subjects must also agree to continue to practice contraceptive methods for at least 6 months following the last dose of study drug.
    3. Stable LDL-cholesterol ≥ 130 mg/dL or 3.36 mmol/L (from at least one of the screening measurements) and triglycerides ≤ 400 mg/dL or 4.55 mmol/L after at least a 12-hour fast
    4. Body mass index (BMI) ≥ 25 kg/m2 and ≤ 32 kg/m2 and stable body weight (±5%) for at least 3 months prior to randomization. Subjects should not have been on any weight-altering or diet modification regimens for 3 months prior to randomization and agree to refrain from such regimens throughout the course of the study, including the post-dose follow-up.
    5. Provide written informed consent to participate in the study prior to any study-specific procedures being performed.
    E.4Principal exclusion criteria
    1. Pregnant women, nursing mothers, or women of childbearing potential.
    2. Subject is directly affiliated with the study, or is an immediate family member of any Study Center personnel directly affiliated with the study.
    3. Subject currently employed by Isis Pharmaceuticals, Inc.
    4. Current diagnosis or history of endocrine, hematologic, renal, hepatic, metabolic (except for primary hypercholesteremia), psychiatric, neurologic, pulmonary, or cardiovascular disease, including any condition that predisposes to secondary hyperlipidemia, such as diabetes mellitus and hypothyroidism.
    5. Current diagnosis or known history of complement deficiency or abnormality.
    6. Positive hepatitis B surface antigen, hepatitis C antibody, or HIV test at screening.
    7. Current diagnosis or known history of liver disease, such as acute or chronic
    hepatitis, liver cirrhosis, liver steatosis, or liver function abnormalities such as
    AST, ALT, GGT, or total bilirubin ≥ 1.5 x ULN at Screening.
    8. Active gallbladder or peptic ulcer disease, or known history of pancreatitis, arterial bleeding, or deep vein thrombosis.
    9. Known history of fibromyalgia, myopathy, rhabdomyolysis, any unexplained muscle pain, or CPK ≥ 1.5 x ULN at screening.
    10. Current diagnosis or known history of a cardiac conditions.
    11. A systolic blood pressure ≥ 160 mmHg or a diastolic blood pressure ≥ 95 mmHg on 2 occasions during screening.
    12. History of cerebrovascular or peripheral vascular disease
    13. History of syncope or seizures
    14. Malignancy within 5 years (with the exception of basal or squamous cell carcinoma of the skin if adequately treated and no recurrence for > 1 year at the time of screening)
    15. Clinically significant abnormalities in coagulation parameters, or is taking any medication that may affect coagulation, such as warfarin, heparin, or fractionated heparin products.
    16. Active infection requiring antiviral or antimicrobial therapy
    17. Currently taking, or taking within 14 days of dosing, any prescription or alternative medication including herbal medication and vitamins (excluding routine multivitamin therapy), which, in the opinion of the investigator, may interfere with the clinical assessment of ISIS 301012. Hormone replacement therapy for post-menopausal women is acceptable. Acetylsalicylic acid (> 75 mg daily), a non-steroidal anti-inflammatory drug, or paracetamol (> 4 g daily), dosed for longer than 5 consecutive days requires pre-approval from Isis. Any other anti-platelet or glycoprotein IIB/IIIa inhibitors should also be avoided. These include ticlopidine, clopidogrel, abciximab, tirofiban hydrochloride, eptifibatide, lamifiban, fradifiban.
    18. Subject has taken any lipid-lowering drug within 30 days or five half-lives (of the lipid-lowering drug) whichever is longer, prior to screening
    19. Alcohol or drug abuse within 2 years of screening
    20. Donated blood (450 mL) within the 3 months prior to screening or suffered significant blood loss equal to a blood donor portion
    21. Subject has known hypersensitivity to ISIS 301012 or similar drugs
    22. Subject not available for follow-up assessment
    23. Subject smokes > 10 cigarettes, or more than one pipe or one cigar per day
    24. Undergoing or have undergone treatment with another investigational drug, biologic agent or device within 90 days prior to screening
    25. Subject suffers any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures



    E.5 End points
    E.5.1Primary end point(s)
    Primary Efficacy Endpoint:
    % reduction in LDL-cholesterol from Baseline to PD14.

    Secondary Efficacy Endpoint:
    % reduction in apoB-100 from Baseline.
    %Change from Baseline in HDL-cholesterol, Triglycerides, Total , non-HDL Cholesterol, VLDL, and Lp(a)
    % Change from Baseline in LDL/HDL and apoB-100/apo-A1 ratios.

    Safety and PK Endpoints:
    All AEs and SAEs
    Physical examination data, vital signs.
    Hepatic, renal, coagulation profiles as measured by AST, ALT, alkaline phosphatase, GGT, total bilirubin, total protein, albumin, BUN, creatinine, aPTT, and PT levels.
    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 Information not present in EudraCT
    E.6.10Pharmacogenetic Information not present in EudraCT
    E.6.11Pharmacogenomic Information not present in EudraCT
    E.6.12Pharmacoeconomic Information not present in EudraCT
    E.6.13Others Information not present in EudraCT
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Information not present in EudraCT
    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) Yes
    E.7.3Therapeutic confirmatory (Phase III) Information not present in EudraCT
    E.7.4Therapeutic use (Phase IV) Information not present in EudraCT
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Information not present in EudraCT
    E.8.1.3Single blind Information not present in EudraCT
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group No
    E.8.1.6Cross over Information not present in EudraCT
    E.8.1.7Other Information not present in EudraCT
    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.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
    E.8.7Trial has a data monitoring committee Information not present in EudraCT
    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 last subject.
    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 days
    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) No
    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 Information not present in EudraCT
    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 state50
    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)
    The subjects will receive their normal expected therapy after the end of the trial.
    Immediately following their last dose of study drug, subjects enter the 6 month post-treatment evaluation period.
    Subjects will be followed up for 6 months post dosing if they discontinue from treatment early.
    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 Decision2005-04-20
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2007-08-29
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2019 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA