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 were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43851   clinical trials with a EudraCT protocol, of which   7283   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).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    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:2011-002944-28
    Sponsor's Protocol Code Number:DM2115403
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2011-12-20
    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 ConcernedNetherlands - Competent Authority
    A.2EudraCT number2011-002944-28
    A.3Full title of the trial
    A phase 2, multi-national, multi-centre, double masked,
    randomised, placebo controlled, parallel-group study to investigate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of darapladib administered for 3 months to adult subjects with diabetic macular edema with centre involvement.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A 3 month Study of Darapladib to Treat Diabetic Macular Edema (DME).
    A.4.1Sponsor's protocol code numberDM2115403
    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 SponsorGlaxoSmithKline Research & Development Limited
    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 supportGlaxoSmithKline Research & Development Limited
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationGlaxoSmithKline
    B.5.2Functional name of contact pointGSK Clinical Support Helpdesk
    B.5.3 Address:
    B.5.3.1Street Address980 Great West Road
    B.5.3.2Town/ cityBrentford
    B.5.3.3Post codeTW8 9GS
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number+44(0)208990 4466
    B.5.5Fax number+44(0)208990 1234
    B.5.6E-mailGSKClinicalSupportHD@gsk.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 No
    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 nameDarapladib
    D.3.2Product code SB-480848
    D.3.4Pharmaceutical form Gastro-resistant 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 INNDarapladib
    D.3.9.2Current sponsor codeSB-480848
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number160
    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 placeboGastro-resistant 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
    Diabetic macular edema with centre involvement
    E.1.1.1Medical condition in easily understood language
    Swelling of the retina (back of the eye) in patients with diabetes , due to leakage of fluid from blood vessels

    E.1.1.2Therapeutic area Diseases [C] - Eye Diseases [C11]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.0
    E.1.2Level LLT
    E.1.2Classification code 10057934
    E.1.2Term Diabetic macular edema
    E.1.2System Organ Class 10015919 - Eye disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To determine the effect of darapladib administered as oral daily doses for 3 months on best-corrected visual acuity (BCVA) and spectral domain OCT (SD-OCT) centre subfield of the study eye in adult subjects with centre-involved DME.
    E.2.2Secondary objectives of the trial
    Secondary Objectives:
    • To determine the effect of darapladib administered as oral daily doses for 3 months on retina anatomy of the study eye in adult subjects with centre-involved DME
    • To assess safety and tolerability of darapladib in adult subjects with centre-involved DME
    • To determine the pharmacokinetic and pharmacodynamic profiles of darapladib in adult subjects with centre-involved DME, as data permit

    Exploratory Endpoints:
    • To determine the effect of darapladib administered as oral daily doses for 3 months on best-corrected visual acuity (BCVA) and spectral domain OCT (SD-OCT) centre subfield in the fellow eye in adult subjects with centre-involved DME
    • To determine the effect of darapladib administered as oral daily doses for 3 months on retina anatomy of the fellow eye in adult subjects with centre-involved DME
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    A subject will be eligible for inclusion in this study only if all of the following criteria apply:
    1. Subject is at least 18 years of age inclusive, at the time of signing the informed consent
    1. A female subject is eligible to participate if she is of:
    • Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol < 40 pg/ml (<147 pmol/L) is confirmatory]
    • Child-bearing potential and agrees to use one of the contraception methods listed in Section 8.1 for an appropriate period of time (as determined by the product label or Investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use
    contraception until follow up visit
    2. Diagnosis of diabetes mellitus (type 1 or type 2)
    3. Confirmation of DME in the study eye by investigator-determined fluorescein angiography
    4. Retinal thickening (diabetic macular edema) involving the centre of the fovea in the study eye as defined by investigator-determined SD-OCT central subfield thickness > 330 microns for Heidelberg Spectralis and >310 for Zeiss Cirrus; if both eyes are eligible, the eye with the greater OCT centre subfield score is selected as the study eye.
    5. Best corrected visual acuity score of 78-24 letters (Snellen equivalent ~20/32 to 20/320) in the study eye
    6. Subject is willing and able to return for all study visits, and is willing and able to comply with all protocol requirements and procedures
    7. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
    E.4Principal exclusion criteria
    A subject will not be eligible for inclusion in this study if any of the following criteria apply:
    Ocular
    1. Additional eye disease in the study eye that could compromise assessment of BCVA or imaging of the posterior pole by fundus photography, fluorescein angiography, or spectral domain OCT, or is likely to require intervention during the ~4 month study
    (e.g. cataract, glaucoma with documented visual field loss, ischemic optic neuropathy, retinitis pigmentosa)
    2. Active proliferative diabetic retinopathy in the study eye
    3. Ischemic maculopathy on fluorescein angiography defined as a total area of capillary loss greater than 2 disc areas (> 5mm2) within the ETDRS macular grid or a foveal avascular zone greatest linear diameter of > 1000 microns
    4. History of choroidal neovascularization in the study eye, or current choroidal neovascularization in the fellow eye requiring treatment
    5. Intraocular surgery in the study eye within 3 months of dosing
    6. Laser photocoagulation in study eye within 3 months of dosing
    7. Use of intravitreal ranibizumab in the study eye within 90 days of dosing
    8. Use of intravitreal bevacizumab in the study eye within 180 days of dosing
    9. Use of intraocular steroids in the study eye within 180 days of dosing
    10. Use of intravitreal bevacizumab in the fellow eye or expected need for intravitreal bevacizumab in the fellow eye during the course of the study
    11. Use of any systemically administered anti-angiogenic agent (e.g., bevacizumab, sunitinib, cetuximab, sorafenib, pazopanib), approved or investigational, within 6 months of dosing
    13. Uncontrolled intraocular pressure >22 mmHg in the study eye despite treatment with glaucoma medication
    14. Within 6 months prior to the Screening Visit, use of medications known to be toxic to the retina, lens or optic nerve (e.g. desferoximine, chloroquine/hydrochloroquine, chlorpromazine, phenothiazines, tamoxifen, and ethambutol)
    Non-ocular
    1. Uncontrolled diabetes as indicated by HbA1c >10% at screening
    2. Evidence of clinical instability or abnormal clinical laboratory findings prior to randomisation that, in the opinion of the Investigator, makes the subject unsuitable for the study
    3. Current liver disease, known hepatic or biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones) or evidence of abnormal liver function tests [total bilirubin or alkaline phosphatase >1.5 x upper limit of normal (ULN); or ALT or AST >2.5 x ULN] or other hepatic abnormalities that in the opinion of the Investigator would preclude the subject from participation in the study
    4. Severe renal impairment (e.g., patients with an estimated glomular filtration rate (GFR) <30 mL/min/1.73m2 or receiving chronic dialysis) or history of nephrectomy or kidney transplant (regardless of renal function)
    5. Poorly controlled hypertension despite lifestyle modifications and pharmacotherapy; systolic blood pressure >160mmHg or diastolic blood pressure >110mmHg (mean of 3 measurements according to protocol-specified conditions)
    6. Current severe heart failure (New York Heart Association class III or IV)
    7. QTcF > 480msec in any subject including those with Bundle Branch Block
    8. Severe asthma that is poorly controlled on pharmacotherapy
    9. History of anaphylaxis, anaphylactoid (resembling anaphylaxis) reactions, or severe allergic responses
    10. A history of known human immunodeficiency virus (HIV) infection
    11. Alcohol or drug abuse within the past 6 months, or current mental condition (psychiatric disorder, senility or dementia), which may affect study compliance or prevent understanding of the aims, investigational procedures or possible consequences of the study
    12. Current or planned chronic administration of strong oral or injectable cytochrome P-450 3A4 (CYP3A4) inhibitors. Note: Examples of strong CYP3A4 inhibitors include, but are not limited to the antiretrovirals atazanavir, indinavir, nelfinavir, ritonavir, saquinavir ; the macrolide antibiotics clarithromycin, telithromycin,
    troleandomycin; and the oral antifungals ketoconazole, itraconazole. Refer to study procedures manual for acceptable treatment alternatives. Of note, weaker CYP3A4 inhibitors are allowed, including verapamil or diltiazem.
    13. Current or planned chronic administration of agents associated with the development of corneal vortex keratopathy, such as amiodarone, chloroquine, suramin and clofazimine [Hollander, 2004]
    14. Previous exposure to darapladib (SB-480848)
    For remaining list of exclusion criteria, please refer to Protocol pg30
    E.5 End points
    E.5.1Primary end point(s)
    Mean change from baseline in ETDRS Best Corrected Visual Acuity (BCVA) and SD-OCT2 centre subfield retinal thickness in the study eye.

    ETDRS = Early Treatment in Diabetic Retinopathy Study
    SD-OCT = Spectral Domain Optical Coherence Tomography
    E.5.1.1Timepoint(s) of evaluation of this end point
    3 months
    E.5.2Secondary end point(s)
    Secondary Endpoints:
    • Changes in retinal anatomy as assessed by fluorescein angiography (leakage area),
    fundus photography (retinal thickening area) and SD-OCT (macular volume, subretinal fluid, intraretinal cysts) in the study eye
    • Safety and tolerability assessed by complete ophthalmic examination, visual acuity,
    vital sign measures (heart rate and blood pressure), clinical laboratory tests, clinical monitoring and adverse event reporting
    • Plasma pharmacokinetic parameters (Cmax, AUC0-t, apparent volume of distribution and apparent clearance, etc) of darapladib as data permit
    • Pharmacodynamic parameters (Lp-PLA2 activity inhibition) of darapladib as data permit
    Exploratory Endpoints:
    • Mean change from baseline in ETDRS Best Corrected Visual Acuity (BCVA) and SD-OCT centre subfield retinal thickness in the fellow eye, as data permit
    • Changes in retinal anatomy as assessed by fluorescein angiography (leakage area),
    fundus photography (retinal thickening area) and SD-OCT (macular volume, subretinal fluid, intraretinal cysts) in the fellow eye, as data permit
    E.5.2.1Timepoint(s) of evaluation of this end point
    Screening and month 3 at a minimum
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    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 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) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number 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 concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA11
    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
    Denmark
    Germany
    Italy
    Netherlands
    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 patient last visit
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years0
    E.8.9.1In the Member State concerned months10
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years0
    E.8.9.2In all countries concerned by the trial months10
    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 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: 26
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 26
    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 state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 39
    F.4.2.2In the whole clinical trial 54
    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)
    Subjects will not receive any additional treatment after completion of the study because darapladib does not have proven efficacy in this indication and other treatment options are available. Subjects may be treated as deemed appropriate by the Investigator following the end of the Treatment Phase. IP will not be available to subjects after the Treatment Phase of this study. Please see pg 48 of Protocol for further details.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation The EMMES Corporation
    G.4.3.4Network Country United States
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2011-12-20
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-01-31
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2013-06-12
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Sat Apr 20 04:22:42 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA