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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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    Summary
    EudraCT Number:2016-003818-26
    Sponsor's Protocol Code Number:K-877-302
    National Competent Authority:Denmark - DHMA
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2017-04-18
    Trial 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 ConcernedDenmark - DHMA
    A.2EudraCT number2016-003818-26
    A.3Full title of the trial
    Pemafibrate to Reduce cardiovascular OutcoMes by reducing triglycerides IN patiENts with diabeTes (PROMINENT)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Pemafibrate to reduce risk of cardiovascular events in patients with diabetes.
    A.4.1Sponsor's protocol code numberK-877-302
    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 Institute, 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 supportKowa Research Institute, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationIQVIA
    B.5.2Functional name of contact pointDavid Sojka
    B.5.3 Address:
    B.5.3.1Street AddressRadlická 714/113a
    B.5.3.2Town/ cityPraha 5
    B.5.3.3Post code158 00
    B.5.3.4CountryCzechia
    B.5.4Telephone number+420775861525
    B.5.6E-maildavid.sojka@quintilesims.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 namePemafibrate
    D.3.2Product code K-877
    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 INNPemafibrate
    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 mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number0.2
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Reduction of cardiovascular events in patients with Type II Diabetes
    E.1.1.1Medical condition in easily understood language
    Diabetic patients with cardiovascular events
    E.1.1.2Therapeutic area Diseases [C] - Cardiovascular Diseases [C14]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level HLT
    E.1.2Classification code 10012654
    E.1.2Term Diabetic complications cardiovascular
    E.1.2System Organ Class 100000004860
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary scientific aim of the PROMINENT study is to assess whether treatment with the selective peroxisome proliferator activated receptor modulator alpha (SPPARM-α), pemafibrate, will prevent myocardial infarction (MI), ischemic stroke, coronary revascularization, and cardiovascular (CV) death in adults with type 2 diabetes (T2D) who have elevated triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) levels and are at high risk for future CV events.
    Specifically, the primary objective of the study is to determine whether pemafibrate administered at a dose of 0.2 mg twice daily will delay the time to first occurrence of any component of the clinical composite endpoint of:
    • nonfatal MI;
    • nonfatal ischemic stroke;
    • coronary revascularization; or
    • CV death.
    E.2.2Secondary objectives of the trial
    The secondary scientific aim of this study is to investigate 1) the efficacy (time to first occurrence) of a number of secondary CV and diabetes-related vascular and nonvascular endpoints in the study population, and 2) the efficacy (as measured by the percent change from baseline) for a number of lipid measures.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Fasting TG ≥ 200 mg/dL (2.26 mmol/L) and < 500 mg/dL (5.65 mmol/L) at Visit 1 (Screening/Enrollment Visit) or Visit 1.1 (Retest)
    2. HDL-C ≤ 40 mg/dL (1.03 mmol/L) at Visit 1 (Screening/Enrollment Visit) or Visit 1.1 (Retest)
    3. Type 2 diabetes of longer than 12 weeks duration documented in medical records, for example: local laboratory evidence through medical record review of elevated HbA1c (≥ 6.5% [48 mmol/mol]), elevated plasma glucose (fasting ≥ 126 mg/dL [7.0 mmol/L], 2-hour ≥ 200 mg/dL [11.1 mmol/L] during oral glucose tolerance testing, or random value ≥ 200 mg/dL with classic symptoms, or currently taking medication for treatment of diabetes; AND either
    a) Age ≥ 50 years if male or ≥ 55 years if female (primary prevention cohort); OR
    b) Age ≥ 18 years and established systemic atherosclerosis (secondary prevention cohort), defined as any 1 of the following:
    i. Prior MI or ischemic (non-hemorrhagic) stroke
    ii. Coronary angiographic lesion of ≥ 60% stenosis in a major epicardial vessel or ≥ 50% left main stenosis
    iii. Asymptomatic carotid disease with ≥ 70% carotid artery stenosis
    iv. Symptomatic carotid disease with ≥ 50% carotid artery stenosis
    v. Symptomatic lower extremity peripheral artery disease (PAD) (ie, intermittent claudication, rest pain, lower extremity ischemic ulceration, or major amputation with either ankle brachial index ≤ 0.9 or other diagnostic testing [eg, toe-brachial index, angiogram, or other imaging study])
    vi. Prior arterial revascularization procedure (including coronary, carotid, or peripheral angioplasty/stenting, bypass, or atherectomy/endarterectomy)
    4. In addition, by Visit 1 (Screening/Enrollment Visit), participants must be either:
    a) Receiving treatment with a stable dose (ie, for at least 12 weeks) of a qualifying moderate- to high intensity statin (atorvastatin ≥ 40 mg/day, rosuvastatin ≥ 20 mg/day, simvastatin ≥ 40 mg/day*, or pitavastatin 4 mg/day); or
    b) Have evidence of LDL-C ≤ 70 mg/dL (1.81 mmol/L) by local laboratory determination within the previous 12 months#, or
    c) Statin intolerant+ and have evidence of LDL-C ≤ 100 mg/dL (2.59 mmol/L) by local laboratory determination within the previous 12 months.
    * Participants enrolled on simvastatin > 40 mg/day must have been taking and tolerating that dose for at least 12 months.
    # If untreated or on stable dosing (ie, for at least 12 weeks) of another lipid-lowering regimen that may include a statin with or without ezetimibe and/or a PCSK9 inhibitor
    + Statin intolerance is defined as: the inability to tolerate at least 2 statins: 1 statin at the lowest daily starting dose (defined as rosuvastatin 5 mg, atorvastatin 10 mg, simvastatin 10 mg, lovastatin 20 mg, pravastatin 40 mg, fluvastatin 40 mg or pitavastatin 2 mg), AND another statin at any dose, due to skeletal muscle-related symptoms, other than those due to strain or trauma, such as pain, aches, weakness, or cramping, that begins or increases during statin therapy and stops when statin therapy is discontinued. Participants not receiving a daily regimen of a statin (e.g., 1-3 times weekly) could also be considered “statin intolerant” if they cannot tolerate a cumulative weekly statin dose of 7 times the lowest approved tablet size, and the criteria outlined above are also met.
    5. Ability to understand and comply with study procedures and give written informed consent.
    E.4Principal exclusion criteria
    1. Current or planned use of fibrates or agents with potent peroxisome proliferator activated receptor (PPAR)-α agonist activity (eg, saroglitazar) within 6 weeks (42 days) of Visit 1 (Screening/Enrollment Visit). Note: PPAR-γ agonists (eg, glizatones such as pioglitazone and rosiglitazone) are allowed
    2. Known sensitivity to PPAR-α agonists or tablet excipients
    3. Initiation of, or change in, current TG-lowering therapy within 12 weeks of Visit 1 (if applicable). Note: TG-lowering therapy is defined as niacin > 100 mg/day or dietary supplements or prescription omega-3 fatty acids > 1 g/day
    4. Type 1 diabetes mellitus
    5.Uncontrolled diabetes mellitus as defined by a HbA1c > 9.5% [80 mmol/mol] at Visit 1 (Screening/Enrollment Visit)
    6.Untreated or inadequately treated hypothyroidism [thyroid stimulating hormone (TSH) > 2.0 X the upper limit of normal (ULN) or free thyroxine (T4) ≤ ULN] or hyperthyroidism; controlled thyroid disease (permitted) requires normal TSH and stable therapy for at least 4 weeks
    7. Recent CVD event (eg, MI or stroke) within 8 weeks of Visit 2 (Randomization Visit)
    8. Recent or planned vascular intervention within 8 weeks of Visit 2
    9. New York Heart Association Class IV heart failure (HF)
    10. Known homozygous familial hypercholesterolemia (heterozygous is permitted) or familial hypoalphalipoproteinemia
    11.Documented previous occurrence of myositis/myopathy
    12.Unexplained creatine kinase (CK) > 5 X ULN
    13.Liver disease defined as cirrhosis or Child-Pugh class B and C, or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 X ULN
    14.Biliary obstruction or hyperbilirubinemia (ie, total bilirubin > 2 X ULN, except with a documented diagnosis of Gilbert’s disease)
    15.Chronic renal insufficiency, defined by an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula or kidney transplant, regardless of renal function
    16.Unexplained anemia (hematocrit ≤ 30%)
    17.Uncontrolled hypertension (seated systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 100 mmHg) at Visit 2 (Randomization Visit).
    18.History of chronic active hepatitis B or hepatitis C, or known infection with HIV; participants with documented hepatitis C resolution after treatment are permitted
    19.Active malignancy, except non-melanoma skin cancer or carcinoma in situ of the cervix, within the last 2 years.
    20.Prior organ transplant or any condition likely to lead to organ transplantation in the next 5 years
    21.Current or anticipated chronic use of cyclosporine, rifampicin, or other inhibitors of organic anion transporting polypeptides (OATP)1B1, or OATP1B3
    22.History of alcoholism or unwillingness to limit alcohol intake to < 15 alcoholic beverages (or units) per week or < 5 alcoholic beverages (or units) during a single occasion for men and < 8 alcoholic beverages (or units) per week or < 4 alcoholic beverages (or units) during a single occasion for women during the study period. Note: One alcoholic beverage (unit) is defined as 12 oz. (350 mL) of beer, 5 oz. (150 mL) of wine, or 1.5 oz. (45 mL) of liquor
    23.History of hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption
    24.Women who are pregnant, lactating, planning to be pregnant or lactating during the study period, or WOCP who are not using an acceptable method of contraception
    25.A medical condition, other than vascular disease, with life expectancy < 3 years, which might prevent the participant from completing the study
    26.Any factors likely to limit adherence to the study medications and procedures, such as substance abuse, dementia, plans to move within the next 2 years, and/or history of noncompliance with medication or scheduled appointments, and
    27.Participation in another clinical study at the time of informed consent, or has received an investigational drug within 90 days before signing the informed consent for this study.
    E.5 End points
    E.5.1Primary end point(s)
    The primary efficacy endpoint is the time from randomization to the first occurrence of any component of the clinical composite endpoint of:
    •Nonfatal MI
    •Nonfatal ischemic stroke
    •Coronary revascularization
    •Cardiovascular death
    E.5.1.1Timepoint(s) of evaluation of this end point
    Variable as event driven
    E.5.2Secondary end point(s)
    The group A (clinical) endpoints are time to first occurrence of:
    - The 4-component composite endpoint of non-fatal MI, non-fatal ischemic stroke, hospitalization for unstable angina requiring unplanned coronary revascularization or cardiovascular death.
    - The 3-component composite endpoint of non-fatal MI, non-fatal ischemic stroke, or cardiovascular death
    - Any component of the primary endpoint or hospitalization for HF.
    - Any component of the primary endpoint or all-cause mortality.
    - Any new or worsening PAD, defined as incidence of lower extremity revascularization, intermittent claudication, rest pain, lower extremity ischemic ulceration, or major amputation with either ankle-brachial index ≤ 0.9 or other diagnostic testing (eg, toe-brachial index, angiogram, or other imaging study).
    - Time of first occurrence of individual endpoints and an analysis of total events (evaluating time to occurrence of the first and all recurrent non-fatal MI, non-fatal ischemic stroke, coronary revascularization, or cardiovascular death).
    - Additionally, as a prespecified secondary analysis, evidence of any genetic effect modification that may relate to pemafibrate and incident cardiovascular events will be evaluated. In particular, whether the effect of pemafibrate as compared with placebo on cardiovascular events differs according to known genetic polymorphisms in the PPARA gene
    (such as, but not limited to rs6008845), will be assessed.
    The group B (lipid) endpoints are:
    • The change from Screening/Enrollment Visit (Visit 1) to Month 4 Visit (Visit 5) for the following lipid biomarkers: TC, TG, HDL-C, non-HDL-C (calculated), VLDL-C (calculated), ApoA1, ApoC3, and ApoE; and
    • The change from Randomization Visit (Visit 2) to Month 6 Visit (Visit 6) for non-fasting remnant cholesterol
    * VLDL-C will be calculated as TC minus HDL-C minus LDL-C, where LDL-C is measured by a direct homogenous method.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Variable with exception of the following carried out at specific visits:
    The change from Screening/Enrollment Visit (Visit 1) to Month 4 Visit (Visit 5) for the following lipid biomarkers: TC, TG, HDL-C, non-HDL-C (calculated), VLDL-C (calculated), ApoA1, ApoC3, and ApoE; and
    • The change from Randomization Visit (Visit 2) to Month 6 Visit (Visit 6) for non-fasting remnant cholesterol
    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 Yes
    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 No
    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 concerned16
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA65
    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
    Brazil
    Bulgaria
    Canada
    Colombia
    Czechia
    Denmark
    France
    Germany
    Hungary
    India
    Israel
    Japan
    Mexico
    Netherlands
    Poland
    Romania
    Russian Federation
    Slovakia
    South Africa
    Spain
    Ukraine
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    Post-study Safety Call up to 30 days after the Common Study End Date (CSED) Visit. The CSED Visit will occur after 1,304 adjudicated and confirmed primary endpoint events have accrued.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years5
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years5
    E.8.9.2In all countries concerned by the trial months0
    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: 4000
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 6000
    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 state150
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 3903
    F.4.2.2In the whole clinical trial 10000
    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)
    Standard of care, not provided by Sponsor.
    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 Decision2017-04-27
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-04-06
    P. End of Trial
    P.End of Trial StatusOngoing
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