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    The EU Clinical Trials Register currently displays   39219   clinical trials with a EudraCT protocol, of which   6426   are clinical trials conducted with subjects less than 18 years old.
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    EudraCT Number:2013-001517-32
    Sponsor's Protocol Code Number:K-877-201
    National Competent Authority:Hungary - National Institute of Pharmacy
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2013-07-26
    Trial results View results
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    A. Protocol Information
    A.1Member State ConcernedHungary - National Institute of Pharmacy
    A.2EudraCT number2013-001517-32
    A.3Full title of the trial
    A dose finding study to assess the safety and efficacy of K-877 in patients with statin-controlled LDL-C but abnormal lipid levels
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    To find a safe and effective dose of K-877 for targeted patients
    A.4.1Sponsor's protocol code numberK-877-201
    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 SponsorKowa Research Europe
    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 supportKowa Research Europe
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationKowa Research Europe
    B.5.2Functional name of contact pointYusuke Senko
    B.5.3 Address:
    B.5.3.1Street Address105 Wharfedale Road
    B.5.3.2Town/ cityWinnersh Triangle, Wokingham
    B.5.3.3Post codeRG41 5RB
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number+440118922 9000110
    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.3.2Product code K-877
    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 848259–27–8
    D.3.9.2Current sponsor codeK-877
    D.3.9.3Other descriptive nameK-877
    D.3.9.4EV Substance CodeSUB119482
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeup to
    D.3.10.3Concentration number400
    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. cell therapy medicinal product No
    D. therapy medical product No
    D. Engineered Product No
    D. ATIMP (i.e. one involving a medical device) No
    D. 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 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
    dyslipidemia (eg hyperlipidaemia, hypertriglyceridaemia)
    E.1.1.1Medical condition in easily understood language
    abnormally high lipid levels
    E.1.1.2Therapeutic area Diseases [C] - Cardiovascular Diseases [C14]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.0
    E.1.2Level LLT
    E.1.2Classification code 10020667
    E.1.2Term Hyperlipidemia
    E.1.2System Organ Class 100000004861
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To assess the dose response of the following parameters:
    •% change in non high density lipoprotein cholesterol (non HDL C) from baseline to Week 12
    •% change in TG from baseline to Week 12

    To assess the safety and tolerability of K 877 in patients with residual cardiovascular risk despite statin controlled LDL C concentration as particularly evaluated by:
    •Change and % change in serum creatinine from baseline to Week 12
    •Change and % change in homocysteine from baseline to Week 12
    E.2.2Secondary objectives of the trial
    To assess the response of the following parameters:
    •% change in HDL C, total cholesterol (TC), and apolipoprotein (Apo) B from baseline to Week 12
    •% change in Apo A1 and Apo A2 from baseline to Week 12
    •% change in LDL C, small LDL particles (small and dense LDL), very low density lipoprotein (VLDL C), Apo B48, Apo B100, Apo C2, Apo C3, adiponectin, fibroblast growth factor 21 (FGF21), high sensitivity C reactive protein (hsCRP), lecithin cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP) mass and activity, proprotein convertase subtilisin/kexin type 9 (PCSK9) mass, HDL function (reverse cholesterol transport, HDL driven endothelial production of nitric oxide, Ion mobility analysis, HDL sub fractions (including pre beta HDL), and lipid and lipoprotein ratios TC/HDL C, non HDL C/HDL C, Apo B/Apo A1, LDL C/Apo B, and Apo C3/Apo C2, from baseline to Week 12
    •To measure PK parameters in a subset of patients per dose group
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Able to understand and comply with study procedures and give written informed consent
    2. Aged ≥18 years
    3. Have no clinically significant abnormal findings on medical history, physical examination, vital signs, 12 lead electrocardiogram (ECG), and clinical laboratory profiles of both blood and urine that would impair participation or safety in the trial or clinically relevant abnormal findings that in the opinion of the investigator could interfere with the objectives of the study or the safety of the patient
    4. After treatment with stable statin therapy for at least 12 weeks prior to screening, have a screening LDL C of no more than 10 mg/dL above the NCEP ATP III target (see Note 2 below):
    • LDL C <70 or <100 mg/dL for patients with CHD or CHD equivalent
    • LDL C <130 mg/dL for patients with multiple risk factors
    • LDL C <160 mg/dL for patients with 0-1 risk factor
    Note 1: Any statin approved by the regulatory authority in the respective country is allowed, with the exception of pravastatin, lovastatin, and fluvastatin
    Note 2: If LDL C is greater than 10 mg/dL above target, patients are only eligible for the study if they are on the maximum allowable statin dose as per approved SPC in the respective country or on the maximum dose tolerated by the respective patient
    5. Fasting TG value at screening is ≥175 mg/dL and ≤500 mg/dL
    Note: If the patient fails to meet this criterion at SV 1, a fasting re test of TG will be allowed at a second SV
    6. HDL C value at screening is ≤50 mg/dL for men and ≤55 mg/dL for women
    7. Women may be enrolled if all 3 of the following criteria are met:
    • They are not pregnant
    • They are not breastfeeding, and
    • They do not plan on becoming pregnant during the study
    8. Women of childbearing potential must have a negative urine pregnancy test at screening. Women are not considered to be of childbearing potential if they meet 1 of the following criteria as documented by the investigator:
    • They have had a hysterectomy or tubal ligation at minimum 1 cycle prior to signing the Informed Consent Form
    • They are post menopausal, defined as ≥1 year since their last menstrual period for women ≥55 years of age or ≥1 year since their last menstrual period and have a follicle stimulating hormone level in menopausal range for women <55 years of age
    9. Women of childbearing potential must agree to use an effective method of contraception from screening to the end of the study. Effective methods of contraception are those contraceptive methods with a Pearl index of <1 used consistently and correctly (including implantable contraceptives, injectable contraceptives, oral contraceptives, transdermal contraceptives, or intrauterine devices
    10. Male study participants will be required to use condoms with a spermicide during sexual intercourse from screening to the end of the study, even if their sexual partner is or may be pregnant
    E.4Principal exclusion criteria
    1. Patients who require other lipid lowering treatments in addition to study drug (K 877) and statin
    2. Patients with body mass index ≥40 kg/m2
    3. Patients with homozygous familial hypercholesterolaemia (heterozygous is permitted) or familial hypoalphalipoproteinaemia
    4. Patients with type 1 diabetes mellitus
    5. Patients with poorly controlled type 2 diabetes mellitus (haemoglobin A1c [HbA1c] >10%)
    6. Patients who are receiving insulin or insulin analog treatment except for stable basal insulin therapy with a single insulin
    7. Patients with moderate or severe renal impairment (ie, estimated glomerular filtration rate <50 mL/min/1.73m2) at screening
    8. Patients with serious liver dysfunction; liver function test values >3 × upper limit of the normal (ULN) of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) at any screening visit
    9. Patients with a creatine kinase (CK) level >3 × ULN at screening
    10. Patients with hepatic insufficiency (including biliary cirrhosis and unexplained persistent liver function abnormalities, eg, persistent increase in serum transaminase), gall bladder disease, or pancreatitis
    11. Patients with a history of drug or alcohol abuse; allowed amounts are 20 g for women and 30 g for men per day (see Appendix D for details on calculating alcohol use)
    12. Patients who have a hypersensitivity/intolerance to PPARĪ± agonists or statins, contraindications as per approved statin Summary of Product Characteristics (SPC)
    13. Patients who had MI, artery angioplasty, bypass graft surgery, or severe/unstable angina pectoris within 3 months prior to screening
    14. Patients who had symptomatic cerebrovascular disease including cerebrovascular haemorrhage, ischaemia, or carotid endarterectomy within 3 months of screening
    15. Patients with symptomatic heart failure (New York Heart Association class III or IV)
    16. Patients who have uncontrolled hypertension (seated systolic blood pressure >160 mmHg and/or diastolic blood pressure >100 mmHg);
    Note: An average of 3 readings within an adequate time interval during the study visit may be used to determine blood pressure level
    17. Patients who have used lipid modifying treatment other than statins 28 days prior to screening
    18. Patients with a history of chronic active hepatitis B or hepatitis C, or known to be infected with human immunodeficiency virus (HIV) 1 or HIV 2
    19. Patients with known muscular or neuromuscular disease
    20. Patients with known active or history (<10 years from previous event) of neoplastic disease (excluding basal cell cancer) or patients who may need to take antineoplastic treatment during the study period
    21. Patients with uncontrolled hypothyroidism or hyperthyroidism
    Note: controlled thyroid disease (normal serum thyroid stimulating hormone [TSH] and stable therapy for at least 3 months) is permitted
    22. Patients who have participated in any other clinical studies within 3 months of screening
    23. Patients who have experienced a loss of more than 400 mL of blood during the 3 months prior to screening, eg, as a blood donor
    24. Patients with a clinically relevant abnormal history, physical examination findings, 12 lead ECG, or laboratory values at screening that in the opinion of the investigator could interfere with the objectives of the study or the safety of the patient
    25. Patient has a high possibility they will not be compliant with the requirements of the protocol
    26. Patients who have a mental condition rendering them unable to understand the nature, scope, and possible consequences of the study
    E.5 End points
    E.5.1Primary end point(s)
    The primary efficacy endpoints of the study include the following:
    • % change in non HDL C from baseline to Week 12
    • % change in TG from baseline to Week 12

    For the primary endpoints, non HDL C and TG, the primary analysis will be carried out using an analysis of covariance (ANCOVA) model with percent change from baseline to Week 12, baseline non HDL C, and baseline TG values as covariates, respectively. The superiority of K 877 groups compared to placebo will be assessed by Dunnett’s test, which will be performed separately for once daily (QD) and twice daily (BID) groups. As a secondary analysis, the dose response relationship in K 877 QD group and BID group will be separately assessed with a contrast method with the ANCOVA model. In addition, the difference between all groups will be assessed with the ANCOVA model. The primary efficacy analysis will be performed on the ITT and Per Protocol Populations.
    The primary efficacy analysis will use the MMRM model for missing data imputation. Sensitivity analysis with LOCF method will be performed. Other possible solutions for the missing data imputation will also be explored, such as repeated measurements at Week 4, Week 8, and Week 12 with compound symmetry covariance structure and repeated measurements at Week 8 and Week 12 with compound symmetry covariance structure.
    E.5.1.1Timepoint(s) of evaluation of this end point
    12 weeks
    E.5.2Secondary end point(s)
    The secondary efficacy endpoints include the following:
    • % change in HDL C, TC, and Apo B from baseline to Week 12
    • % change in Apo A1 and Apo A2 from baseline to Week 12
    • % change in LDL C, small LDL particles (small and dense LDL), VLDL C, Apo B48, Apo C2, Apo C3, adiponectin, FGF21, hsCRP, LCAT, CETP mass and activity, PCSK9 mass, HDL function (reverse cholesterol transport, HDL driven endothelial production of nitric oxide, Ion mobility analysis, HDL sub-fractions (including pre beta HDL), and lipid and lipoprotein ratios TC/HDL C, non HDL C/HDL C, Apo B/Apo A1, LDL C/Apo B and Apo C3/C2 from baseline to Week 12

    The secondary efficacy endpoints will be analysed using the same statistical method used for the primary analysis; however, Dunnett’s test will not be used to evaluate the superiority of the K 877 groups to the placebo group.
    E.5.2.1Timepoint(s) of evaluation of this end point
    12 weeks
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic 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 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. 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 trial7
    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 concerned12
    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 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
    Czech Republic
    Russian Federation
    United Kingdom
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months4
    E.8.9.1In the Member State concerned days14
    E.8.9.2In all countries concerned by the trial months4
    E.8.9.2In all countries concerned by the trial days14
    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: 350
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 350
    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 state80
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 200
    F.4.2.2In the whole clinical trial 350
    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)
    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 Decision2013-09-19
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2013-09-09
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2014-09-23
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