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    The EU Clinical Trials Register currently displays   44334   clinical trials with a EudraCT protocol, of which   7366   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).

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    Summary
    EudraCT Number:2018-003852-19
    Sponsor's Protocol Code Number:DOAC
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2019-03-18
    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 number2018-003852-19
    A.3Full title of the trial
    An Open Label, Non-Randomised, Phase IV Clinical Trial to Determine the Transfer of Apixaban and Rivaroxaban in Breast Milk Following Oral Administration
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    An Open Label, Non-Randomised, Phase IV Clinical Trial to Determine the Transfer of Apixaban and Rivaroxaban in Breast Milk Following Oral Administration
    A.3.2Name or abbreviated title of the trial where available
    Apixaban and rivaroxaban in breast milk
    A.4.1Sponsor's protocol code numberDOAC
    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 SponsorKing's College London
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportKing's College London
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationKing's College London
    B.5.2Functional name of contact pointRoopen Arya
    B.5.3 Address:
    B.5.3.1Street AddressDepartment of Haematological Medicine, King’s College Hospital, Denmark Hill,
    B.5.3.2Town/ cityLondon
    B.5.3.3Post codeSE5 9RS
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number+4402032993570
    B.5.6E-mailroopen.arya@nhs.net
    B.Sponsor: 2
    B.1.1Name of SponsorKing's College Hospital NHS Foundation Trust
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportKings College London
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationKing's college Hospital NHS Foundation Trust
    B.5.2Functional name of contact pointRoopen Arya
    B.5.3 Address:
    B.5.3.1Street AddressDepartment of Haematological Medicine, King’s College Hospital, Denmark Hill
    B.5.3.2Town/ cityLondon
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number+4402032993570
    B.5.6E-mailroopen.arya@nhs.net
    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 Yes
    D.2.1.1.1Trade name Xarelto
    D.2.1.1.2Name of the Marketing Authorisation holderBayer AG
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 nameRivaroxaban
    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.3.8INN - Proposed INNRIVAROXABAN
    D.3.9.1CAS number 366789-02-8
    D.3.9.4EV Substance CodeSUB29263
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    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.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 Yes
    D.2.1.1.1Trade name Eliquis
    D.2.1.1.2Name of the Marketing Authorisation holderBristol-Myers Squibb/Pfizer EEIG
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 nameApixaban
    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.3.8INN - Proposed INNAPIXABAN
    D.3.9.1CAS number 503612-47-3
    D.3.9.4EV Substance CodeSUB25425
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    healthy volunteers (Venous Thromboembolism)
    E.1.1.1Medical condition in easily understood language
    healthy volunteers (Blood clots during breast feeding)
    E.1.1.2Therapeutic area Diseases [C] - Blood and lymphatic diseases [C15]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10049909
    E.1.2Term Venous thromboembolism prophylaxis
    E.1.2System Organ Class 100000004865
    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 if apixaban and rivaroxaban are excreted in breastmilk following single dose oral administration to breastfeeding mothers.
    E.2.2Secondary objectives of the trial
    To evaluate the concentration-time profiles of apixaban and rivaroxaban in the plasma and breastmilk of breastfeeding mothers, and therefore to establish the potential exposure of breastfed infants to apixaban and rivaroxaban
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Subject is informed and given ample time and opportunity to think about his/her participation and has provided written informed consent for participation in the study before any study specific procedures take place.
    2. Subject is considered reliable and capable of adhering to applicable protocol requirements, including the study drug being administered orally and visit schedule according to the judgement of the Investigator.
    3. Women are aged ≥18 years.
    4. At least 6 weeks postpartum when enter the study.
    5. Decision has been confirmed by the woman to stop breastfeeding their baby soon.
    6. Negative pregnancy test.
    7. Good physical and mental health, in the opinion of the Investigator, determined on the basis of medical history and general clinical examination at Screening.
    8. Women have clinical laboratory test results within the reference ranges of the testing laboratory: normal renal function test – results of the serum creatinine <90 micro mol/L. Normal liver function tests – results of the serum ALT </= 40 IU/L.
    9. Women are not taking any medication interacting with apixaban or rivaroxaban, as listed in table 6.4 and 6.5.
    10. Women are available to attend scheduled visits at clinical unit and permit the clinic staffs visit home to collect blood and milk samples.
    11. Women agree to the study restrictions
    E.4Principal exclusion criteria
    1. Women who are unable to provide written informed consent.
    2. LMWH thromboprophylaxis is indicated.
    3. Increased risk of bleeding for any reason.
    4. Known contra-indications to apixaban or rivaroxaban.
    5. On-going treatment with aspirin, NSAIDs or other drugs that affect haemostasis.
    6. Treatment with oral ketoconazole or itraconazole, medicines to treat fungal infections.
    7. Patients who have received an artificial heart valve, have had a heart attack or suffer an irregular heartbeat (including taking dronedarone).
    8. Known impaired renal function (serum creatinine > 90 micro mol/L).
    9. Known abnormal liver function tests (ALT > 40 IU/L).
    10. Known hypersensitivity or allergy to apixaban or rivaroxaban.
    11. Use of other investigational study drugs within 30 days prior to study entry.
    12. Women who are pregnant or of childbearing potential who refuse to use an acceptable effective form of contraception throughout the study.
    13. Women who will not participate in study visits within a suitable distance from King’s College Hospital NHS Foundation Trust, as judged by the investigator.
    E.5 End points
    E.5.1Primary end point(s)
    Apixaban and its metabolites in plasma and breast milk will be measured at 0, 3-4, 7, 12, 14, 16, 24 hours after swallowing two 5mg capsules of apixaban (1 capsule 12 hours apart).
    Rivaroxaban in plasma and breast milk will be measured at 0, 2-3, 6, 10, 12, 24 hours after swallowing one 20mg tablet of rivaroxaban.
    Milk sampling from both breasts will be done at each time point.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Apixaban and its metabolites in plasma and breast milk will be measured at 0, 3-4, 7, 12, 14, 16, 24 hours after swallowing two 5mg capsules of apixaban (1 capsule 12 hours apart).
    Rivaroxaban in plasma and breast milk will be measured at 0, 2-3, 6, 10, 12, 24 hours after swallowing one 20mg tablet of rivaroxaban.
    Milk sampling from both breasts will be done at each time point.
    E.5.2Secondary end point(s)
    The following PK parameters for apixaban and rivaroxaban in milk and plasma will be the endpoints: Area under the concentration-time curve (AUC) from zero to the time of the last quantifiable concentration (AUC(0-t)); AUC from zero to the time of 24 hours (AUC(0-24)).
    E.5.2.1Timepoint(s) of evaluation of this end point
    0 to 24 hours
    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 No
    E.6.5Efficacy No
    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) No
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) Yes
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    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) Yes
    E.8.2.2Placebo No
    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
    Database lock
    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 months6
    E.8.9.1In the Member State concerned days31
    E.8.9.2In all countries concerned by the trial years0
    E.8.9.2In all countries concerned by the trial months6
    E.8.9.2In all countries concerned by the trial days31
    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: 4
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male No
    F.3 Group of trial subjects
    F.3.1Healthy volunteers Yes
    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 Yes
    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 state4
    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)
    None
    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 Decision2019-03-29
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-02-21
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2020-07-15
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