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   43871   clinical trials with a EudraCT protocol, of which   7290   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:2018-000970-31
    Sponsor's Protocol Code Number:CV013-034
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2018-06-12
    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 ConcernedUK - MHRA
    A.2EudraCT number2018-000970-31
    A.3Full title of the trial
    A Randomized, Double-Blind, Placebo-Controlled, Cross-over Phase 2 Study of Continuous 8 Hour Intravenous Infusions of BMS-986231 in Patients with Heart Failure and Impaired Systolic Function Given a Standard Dose of Loop Diuretic
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study designed to evaluate the effects of BMS-986231 versus placebo on urine output when taken with a single dose of a diuretic (furosemide). BMS-986231 or Placebo are provided in the form of Intravenous Infusions for a duration of 8 hours, with furosemide given after 4 hours, in patients whose heart is unable to pump sufficiently (chronic heart failure); exposed to each of the 2 interventions over the course of the study.
    A.4.1Sponsor's protocol code numberCV013-034
    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 SponsorBristol-Myers Squibb International Corporation
    B.1.3.4CountryBelgium
    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 supportBristol-Myers Squibb International Corporation
    B.4.2CountryBelgium
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationBristol-Myers Squibb International Corporation
    B.5.2Functional name of contact pointGCT-SU
    B.5.3 Address:
    B.5.3.1Street AddressParc de l'Alliance - Avenue de Finlande, 4
    B.5.3.2Town/ cityBraine-l'Alleud
    B.5.3.3Post code1420
    B.5.3.4CountryBelgium
    B.5.6E-mailclinical.trials@bms.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 nameBMS-986231-01 for Injection, 240 mg/vial
    D.3.2Product code BMS-986231
    D.3.4Pharmaceutical form Powder for concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNHNO
    D.3.9.1CAS number 1620330-72-4
    D.3.9.2Current sponsor codeCV013-034
    D.3.9.3Other descriptive nameBMS986231
    D.3.9.4EV Substance CodeSUB182812
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number240
    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 placeboConcentrate for solution for infusion
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Heart failure with reduced ejection fraction (HFrEF)
    E.1.1.1Medical condition in easily understood language
    Inability of the heart to pump sufficiently to maintain blood flow to meet the body's needs.
    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 LLT
    E.1.2Classification code 10074631
    E.1.2Term Systolic heart failure
    E.1.2System Organ Class 100000004849
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10019279
    E.1.2Term Heart failure
    E.1.2System Organ Class 100000004849
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Evaluate the effects of HNO donor BMS-986231 on 4-hour urine output in patients with HFrEF after administration of 40 mg of IV furosemide
    E.2.2Secondary objectives of the trial
    - Assess the effect of BMS-986231 on fractional excretion of Na (FeNa)
    - Assess the effect of BMS-986231 on fractional excretion of K (FeK)
    - Assess the effects of BMS-986231 on furosemide urinary and plasma concentration and the ratio urinary sodium to urinary furosemide
    - Assess safety of BMS-986231
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1) Signed Written Informed Consent
    a) Subjects will be required to provide a written informed consent.

    2)Type of Participant and Target Disease Characteristics
    a) Males and Females, ages 18 or age of majority or older.
    b) Left ventricular EF <45%, as assessed by echocardiography, a multigated acquisition (MUGA) scan or magnetic resonance imaging (MRI) scan within 18 months.
    c) On stable chronic guideline-directed therapy for HF including chronic loop diuretics, ACEi, ARBs, MRAs, ARNI or / and β-blockers as tolerated, with no changes of these medications in the past 2 weeks.
    d) Not applicable per Protocol Amendment 3.0
    e) Not applicable per Protocol Amendment 3.0
    f) Not applicable per Protocol Amendment 3.0
    g) Elevated natriuretic peptides (N terminal-pro BNP [NT-proBNP] ≥ 200 pg/mL or brain natriuretic peptide [BNP] ≥ 60 pg/mL). For subjects with atrial fibrillation, NT-proBNP ≥ 400 pg/mL or BNP ≥ 120 pg/mL.
    h) Estimated glomerular filtration rate (eGFR) between 30 and 80 mL/min/1.73m2.

    3) Age and Reproductive Status
    a) Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 24 hours prior to the start of each study treatment.
    b) Women must not be breastfeeding.
    c) WOCBP must agree to follow instructions for methods of highly effective contraception for 31 days after discontinuation (duration of study drug exposure plus 30 days duration of one ovulatory cycle).
    d) Males who are sexually active with WOCBP must require these partners to follow instructions for highly effective methods of contraception for 91 days after discontinuation (duration of study drug plus 90 days (duration of sperm turnover).
    e) Azoospermic males are exempt from contraceptive requirements. WOCBP who are continuously not heterosexually active are also exempt from contraceptive requirements, but still must undergo pregnancy testing as described in this section.

    Investigators shall advise on the use of highly effective methods of contraception, which have a failure rate of < 1% when used consistently and correctly.
    Local laws and regulations may require use of alternative and/or additional contraception methods.
    E.4Principal exclusion criteria
    1)Target Disease Exceptions
    a) SBP < 115 mm Hg or > 180 mm Hg at screening or pre-randomization.
    b) Heart rate < 50 beats per minute (bpm) or > 120 bpm at screening or pre-randomization.
    c) Primary HF etiology attributable to either restrictive/obstructive cardiomyopathy, idiopathic hypertrophic or uncorrected severe valvular disease as defined by American Heart Association (AHA)/American College of Cardiology (ACC)/European Society of Cardiology (ESC) criteria.
    d) Patients with urinary/prostate disorders with urinary retention/significant bladder dysfunction or urinary incontinence.
    e) Inability to comply with the serial urine collection procedures.
    f) Pericardial tamponade or constrictive pericarditis.
    g) Left ventricular (LV) assist device or prior heart transplant.
    h) Hospitalized for acute decompensated HF in the previous month.
    i) New York Heart Association (NYHA) Class IV symptoms of HF.
    j) Hospitalized with acute coronary syndrome, coronary revascularization or acute myocardial infarction during the previous 90 days prior to screening.
    k) Have a history of a cerebral vascular accident (cerebrovascular accident [CVA] or stroke) or of a transient ischemic attack (TIA) during the previous 90 days prior to screening.
    l) Considered clinically unstable for any condition.
    m) Serious comorbid non-cardiovascular disease in which the life expectancy of the subject is < 3 months.
    n) Liver disease defined as history of cirrhosis with evidence of portal hypertension such as varices, or encephalopathy, or total bilirubin > 3 mg/dL (> 34.2 μmol/L) or significant elevation of liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT] > 3 times the upper limit of normal).
    o) Prior solid organ transplant.

    2)Prior/Concomitant Therapy
    a) Patients taking thiazides / metolazone or potassium-sparing diuretics (with the exception of spironolactone or eplerenone at doses ≤ 50 mg/day which are allowed).

    3)Physical and Laboratory Test Findings
    a) Have persistent abnormal serum electrolytes not resolved between screening and start of the study drug infusion, as defined by any of the following:
    i)A sodium (Na+) concentration < 130 or > 145 mEq/L (mmol/L).
    ii)A potassium (K+) concentration < 3.2 or > 5.5 mEq/L (mmol/L).
    b) Have severe anemia, as documented by a hemoglobin < 9 g/dL (< 5.59 mmol/L).

    4)Allergies and Adverse Drug Reaction
    a) Any history of allergic reaction to components of BMS-986231, Captisol® or potassium acetate.
    b) Any history of allergic reactions to furosemide.

    5)Other Exclusion Criteria
    a) Prisoners or participants who are involuntarily incarcerated. (Note: under certain specific circumstances a person who has been imprisoned may be included or permitted to continue as a participant. Strict conditions apply and Bristol-Myers Squibb’s approval is required).
    b) Participants who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness.
    c) Participation in an investigational clinical drug study within 30 days or 5 elimination half-lives, (whichever is longer) prior to randomization.
    d) Prior participation and treatment in a study using BMS-986231.
    e) Alcohol beverage consumption within 6 hours prior to randomization.
    f) Body weight < 45 kg or ≥ 140 kg.
    g) Site personel and their families.
    E.5 End points
    E.5.1Primary end point(s)
    4-hour urinary output following intravenous administration of 40 mg furosemide to HFrEF patients receiving BMS-986231 infusion compared to placebo
    E.5.1.1Timepoint(s) of evaluation of this end point
    At the end of the 8-hour infusion
    E.5.2Secondary end point(s)
    - FeNa in patients with HFrEF while on BMS 986231 compared to placebo
    - FeK in patients with HFrEF while on BMS 986231 compared to placebo
    - Furosemide urinary and plasma concentration in patients with HFrEF while on BMS-986231 compared to placebo
    - Ratio Urinary Na to Urinary furosemide after BMS 986231 compared to placebo
    - Clinically relevant hypotension during infusion, AEs, clinical laboratory values, vital signs, ECGs, telemetry, physical examinations.
    E.5.2.1Timepoint(s) of evaluation of this end point
    During and at the end of the 8-hour infusion
    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 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.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 No
    E.8.1.6Cross over Yes
    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 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 No
    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
    End of trial is defined as the last visit or scheduled procedure for the last participant.
    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 months2
    E.8.9.1In the Member State concerned days27
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months2
    E.8.9.2In all countries concerned by the trial days27
    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: 15
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 5
    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 state20
    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)
    At the end of the study, BMS will not continue to provide BMS supplied study treatment to participants/investigators unless BMS chooses to extend the study. The investigator should ensure that the participant receives appropriate standard of care to treat the condition under study.
    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 Decision2018-07-25
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-09-10
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2020-01-09
    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-Fri May 03 06:24:34 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA