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   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).

    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:2021-005366-17
    Sponsor's Protocol Code Number:2020/ABM/01/00100
    National Competent Authority:Poland - Office for Medicinal Products
    Clinical Trial Type:EEA CTA
    Trial Status:Trial now transitioned
    Date on which this record was first entered in the EudraCT database:2022-02-09
    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 ConcernedPoland - Office for Medicinal Products
    A.2EudraCT number2021-005366-17
    A.3Full title of the trial
    Evaluation of METtformin effect on the fertility of patients treated with 131I for THYRoid cancer – METHYR Study.
    Ocena wpływu metforminy na płodność pacjentek leczonych 131l z powodu raka brodawkowego tarczycy
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Evaluation of METtformin effect on the fertility of patients treated with 131I for THYRoid cancer.
    Ocena wpływu metforminy na płodność pacjentek leczonych 131l z powodu raka brodawkowego tarczycy
    A.3.2Name or abbreviated title of the trial where available
    METHYR
    A.4.1Sponsor's protocol code number2020/ABM/01/00100
    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 SponsorMedical University of Bialystok
    B.1.3.4CountryPoland
    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 supportAgencja Badań Medycznych
    B.4.2CountryPoland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMedical University of Bialystok/Professor Agnieszka Adamska MD.PhD
    B.5.2Functional name of contact pointNational coordinator
    B.5.3 Address:
    B.5.3.1Street AddressM.C. Skłodowskiej 24 A
    B.5.3.2Town/ cityBiałystok
    B.5.3.3Post code15-276
    B.5.3.4CountryPoland
    B.5.4Telephone number+4885 74 68 239
    B.5.6E-mailagnieszka.adamska@umb.edu.pl
    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 GLUCOPHAGE 500mg
    D.2.1.1.2Name of the Marketing Authorisation holderMerck Sante s.a.s. 37, rue Saint-Romain 69008 Lyon Francja
    D.2.1.2Country which granted the Marketing AuthorisationFrance
    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.3.4Pharmaceutical form 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 INNMETFORMIN HYDROCHLORIDE
    D.3.9.1CAS number 1115-70-4
    D.3.9.4EV Substance CodeSUB03200MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number500
    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 placeboCoated 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
    Thyroid papilare cancer
    Rak brodawkowy tarczycy
    E.1.1.1Medical condition in easily understood language
    Thyroid cancer is a disease in which malignant (cancer) cells form in the tissues of the thyroid gland.
    Rak tarczycy to choroba, w której w tkankach tarczycy tworzą się komórki nowotworowe (rakowe).
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10066474
    E.1.2Term Thyroid cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Primary objectives
    • To evaluate the efficacy of metformin on female fertility who were subjected to 131l treatment – ovarian reserve markers which are shown as AMH, inhibin B and FSH level in serum and antral follicle count checked by ultrasound.
    • Ocena skuteczności wpływu metforminy na pośrednie markery rezerwy jajnikowej (tj. stężenie AMH w surowicy, liczba pęcherzyków antralnych w badaniu usg) u kobiet, które zostały poddane leczeniu 131l.
    E.2.2Secondary objectives of the trial
    Safety Objectives
    • Incidence of adverse events (AEs) and serious adverse events (SAEs) and changes in laboratory measurements
    Exploratory objectives
    • Patient reported outcome (PRO) for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires (QLQ-THY34)
    • Medical Resource Utilization (MRU)
    Bezpieczeństwa
    • Częstotliwość występowania skutków ubocznych (AE) i poważnych skutków ubocznych w badaniach laboratoryjnych
    Poznawcze
    • Ocena jakości życia za pomocą kwestionariusza (Patient Reported Outcome PRO for Research and Treatment of Cancer - QLQ-THY34) formularz dedykowany dla pacjetów z nowotworem tarczycy.
    • Analiza utylizacji zasobów medycznych
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Female subjects in reproductive age >18 <45
    2. Subjects with diagnosed papillary thyroid carcinoma with various pathological stage TNM (I-II)
    3. Subjects not treated with 131l
    4. Willingness to comply with protocol procedures
    1. Pacjentki w okresie reprodukcyjnym >18 <45
    2. Pacjentki ze zdiagnozowanym rakiem brodawkowatym tarczycy w różnym stadium zaawansowania TNM (I-II)
    3. Pacjentki, które nie zostały jeszcze poddane leczeniu jodem radioaktywnym
    4. Stężenie TSH w surowicy 0.1-4.9mU/l
    5. Chęć stosowania się procedur protokołu
    E.4Principal exclusion criteria
    1. Hypersensitivity to metformin
    2. Subjects with polycystic ovarian syndrome or other diseases of the ovaries (primary / secondary ovarian failure)
    3. Subjects who take metformin during last week
    4. Subjects with liver malfunction and abnormal liver tests results (ALT and AST activity >3ULN
    5. Subjects with eGFR below 45 ml/min/1.73m2
    6. Subjects with lactic acidosis or who have history of metabolic acidosis
    7. Subjects with serum AMH concentration below lower range norm
    8. Subjects with history of congestive heart disease NYHA stage III/IV
    9. Subjects with acute myocardial ischemia (CCS 3-4)
    10. Subjects with history of sepsis or severe infection
    11. Subjects with lung disease (uncontrolled Asthma based on GINA 2000 Guidelines and COPD GOLD≥3 stage)
    12. Positive result of pregnancy test or planned pregnancy during the study
    13. Alcohol dependent syndrome
    14. BMI <18.5 kg/m2
    15. Accompanying diseases with poor prognosis in the opinion of the researcher
    16. As per the Investigator (or his designee) judgment, subject cannot participate in the study due to reasons (i.e. medical, psychiatric and/or social reason)
    17. Unreliability or lack of cooperation
    1. Nadwrażliwość na metforminę
    2. Pacjentki z zespołem policystycznych jajników lub innymi schorzeniami jajników (pierwotną/wtórną niewydolnością jajników)
    3. Pacjentki przyjmujące metforminę w ostatnim tygodniu
    4. Pacjentki z zaburzeniami czynności wątroby i nieprawidłowymi wynikami testów czynnościowych wątroby (aktywność ALT/AST powyżej 3x ggn)
    5. Pacjentki z eGFR poniżej 45 ml/min/1.73m2
    6. Pacjentki z kwasicą mleczanową lub inną kwasicą metaboliczną w wywiadzie
    7. Pacjentki u których stężenie AMH w surowicy jest poniżej granicy normy
    8. Pacjentki z zastoinową niewydolnością serca w wywiadzie III/IV stopień wg NYHA
    9. Pacjentki z ostrym niedokrwieniem mięśnia sercowego (CCS-3.4)
    10. Pacjentki z posocznicą lub ciężką infekcją w wywiadzie
    11. Pacjentki z chorobami płuc w wywiadzie (niekontrolowana astma – wytyczne GINA 2000 i COPD GOLD ≥ stadium 3)
    12. Dodatni wynik testu ciążowego lub planowa ciąża w trakcie trwania badania
    13. Zespół zależności alkoholowej
    14. BMI poniżej 18.5 kg/m2
    15. Towarzyszące choroby przewlekłe o złym rokowaniu w opinii badacza
    16. Zgodnie z osądem badacza (lub osoby przez niego wyznaczonej), pacjentka nie może uczestniczyć w badaniu z innych powodów (tj. medycznych, psychiatrycznych i/lub społecznych)
    17. Nierzetelność lub brak współpracy
    E.5 End points
    E.5.1Primary end point(s)
    • The primary endpoint will be to evaluate the effect of metformin on the difference in serum AMH, inhibin B and FSH concentration and the number of antral follicles in ultrasonography, between the study groups in women with papillary thyroid cancer treated with 131I, between the randomized visit and V3, V4, V5 and V6 visit
    • Pierwszorzędowym punktem końcowym będzie ocena wpływu metforminy na różnicę w stężeniu AMH, inhibiny B i FSH w surowicy i liczbie pęcherzyków antralnych ocenianych w badaniu usg, między badanymi grupami u kobiet z rakiem brodawkowatym tarczycy, leczonych 131I między wizytą randomizowaną a wizytą V3, V4, V5 i V6
    E.5.1.1Timepoint(s) of evaluation of this end point
    On a visit of 2 – m3, a visit of 3 – m6 and a visit of 4 -m9 and one year after administration of I131.
    The first interim analysis will be performed when 15% of the participants have completed the annual observation period according to the protocol. The second interim analysis will be performed when 45% of the participants have completed the one-year observation period according to the protocol.
    Na wizycie 2 – m3, wizycie 3 – m6 i wizycie 4-m9 i rok po podaniu I131.Pierwsza analiza okresowa zostanie wykonana, gdy 15% uczestniczek zakończy roczny okres obserwacji zgodnie z protokołem. Druga analiza okresowa zostanie przeprowadzona, gdy 45% uczestniczek zakończy roczny okres obserwacji zgodnie z protokołem.
    E.5.2Secondary end point(s)
    • To evaluate the effect of metformin on the difference in serum concentration of selected parameters of oxidative stress between the study groups in women with papillary thyroid cancer treated with 131I between the randomized visit and V3, V4, V5 and V6 visit
    • To evaluate the effect of metformin on the difference in serum concentration of selected parameters of apoptosis between the study groups in women with papillary thyroid cancer treated with 131I between the randomized visit and V3, V4, V5 and V6 visit
    • To evaluate the effect of metformin on the difference of expression in selected microRNA between the study groups in women with papillary thyroid cancer treated with 131I between the randomized visit and V3, V4, V5 and V6 visit
    • Assessment of the quality of life using the QLQ-THY34 questionnaire dedicated to patients with thyroid cancer
    • Characteristics and tolerability of standard metformin dosage in patient with papillary thyroid cancer
    • Frequency of AEs requiring discontinuation of study drug or dose reduction
    • Change in basic laboratory assessment between visits
    • Ocena wpływu metforminy na różnicę stężeniach w surowicy wybranych parametrów stresu oksydacyjnego między badanymi grupami u kobiet z rakiem brodawkowatym tarczycy leczonych 131I między wizytą randomizacyjną a wizytą V3, V4, V5 i V6
    • Ocena wpływu metforminy na różnicę w stężeniach w surowicy wybranych parametrów apoptozy między badanymi grupami, u kobiet z rakiem brodawkowatym tarczycy leczonych 131I, między wizytą randomizowaną a wizytą V3, V4, V5 i V6
    • Ocena wpływu metforminy na różnicę w ekspresji wybranych mikroRNA między badanymi grupami, u kobiet z rakiem brodawkowatym tarczycy leczonych 131I, między wizytą randomizowaną a wizytą V3, V4, V5 i V6
    • Ocena jakości życia za pomocą kwestionariusza QLQ-THY34 dedykowanego dla pacjentek z rakiem tarczycy
    • Charakterystyka i tolerancja standardowego dawkowania metforminy u pacjenta z rakiem brodawkowatym tarczycy
    • Częstość zdarzeń niepożądanych wymagających przerwania stosowania badanego leku lub zmniejszenia dawki
    • Zmiana w podstawowych wynikach badań laboratoryjnych pomiędzy wizytami
    E.5.2.1Timepoint(s) of evaluation of this end point
    On a visit of 2 – m3, a visit of 3 – m6 and a visit of 4 -m9 and one year after administration of I131. The first interim analysis will be performed when 15% of the participants have completed the one-year observation period according to the protocol. The second interim analysis will be conducted when 45% of the participants have completed the annual observation period according to the protocol.
    Na wizycie 2 – m3, wizycie 3 – m6 i wizycie 4-m9 i rok po podaniu I131. Pierwsza analiza okresowa zostanie wykonana, gdy 15% uczestniczek zakończy roczny okres obserwacji zgodnie z protokołem. Druga analiza okresowa zostanie
    Strona 15 z 23
    przeprowadzona, gdy 45% uczestniczek zakończy roczny okres obserwacji zgodnie z protokołem.
    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 No
    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.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 trial3
    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 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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months2
    E.8.9.1In the Member State concerned days
    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: 160
    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 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 state160
    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)
    After the end of study patients will be treated according to standard of care.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2022-09-14
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2022-01-20
    P. End of Trial
    P.End of Trial StatusTrial now transitioned
    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 02 19:39:04 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA