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    Summary
    EudraCT Number:2012-005499-33
    Sponsor's Protocol Code Number:HP5503-88
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2014-10-07
    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 ConcernedGermany - BfArM
    A.2EudraCT number2012-005499-33
    A.3Full title of the trial
    Relative bioavailability trial to investigate the pharmacokinetics of tapentadol following the administration of 3 prototype tapentadol 25 mg prolonged release (PR) granule formulations compared to a Palexia® PR 25 mg tablet in healthy adult subjects.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Comparison of blood concentrations of tapentadol from 4 prolonged release formulations (3 granule formulations and 1 tablet formulation) in healthy adult subjects.
    A.4.1Sponsor's protocol code numberHP5503-88
    A.5.3WHO Universal Trial Reference Number (UTRN)U1111-1159-4436
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/095/2014
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorGrünenthal GmbH
    B.1.3.4CountryGermany
    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 supportGrünenthal GmbH
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationGrünenthal GmbH
    B.5.2Functional name of contact pointGrünenthal Clinical Trial Helpdesk
    B.5.3 Address:
    B.5.3.1Street AddressZieglerstr. 6
    B.5.3.2Town/ cityAachen
    B.5.3.3Post code52078
    B.5.3.4CountryGermany
    B.5.4Telephone number+49241569 3223
    B.5.6E-mailClinical-Trials@grunenthal.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 nameTapentadol 25 mg prolonged-release granules 15% coating level
    D.3.2Product code CG5503
    D.3.4Pharmaceutical form Prolonged-release granules
    D.3.4.1Specific paediatric formulation Yes
    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 INNTAPENTADOL HYDROCHLORIDE
    D.3.9.1CAS number 175591-09-0
    D.3.9.2Current sponsor codeCG5503
    D.3.9.3Other descriptive nameTAPENTADOL HYDROCHLORIDE
    D.3.9.4EV Substance CodeSUB32145
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    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 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 nameTapentadol 25 mg prolonged-release granules 20% coating level
    D.3.2Product code CG5503
    D.3.4Pharmaceutical form Prolonged-release granules
    D.3.4.1Specific paediatric formulation Yes
    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 INNTAPENTADOL HYDROCHLORIDE
    D.3.9.1CAS number 175591-09-0
    D.3.9.2Current sponsor codeCG5503
    D.3.9.3Other descriptive nameTAPENTADOL HYDROCHLORIDE
    D.3.9.4EV Substance CodeSUB32145
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    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: 3
    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 nameTapentadol 25 mg prolonged-release granules 25% coating level
    D.3.2Product code CG5503
    D.3.4Pharmaceutical form Prolonged-release granules
    D.3.4.1Specific paediatric formulation Yes
    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 INNTAPENTADOL HYDROCHLORIDE
    D.3.9.1CAS number 175591-09-0
    D.3.9.2Current sponsor codeCG5503
    D.3.9.3Other descriptive nameTAPENTADOL HYDROCHLORIDE
    D.3.9.4EV Substance CodeSUB32145
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    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: 4
    D.1.2 and D.1.3IMP RoleComparator
    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 Palexia retard 25mg Retardtabletten
    D.2.1.1.2Name of the Marketing Authorisation holderGrünenthal GmbH
    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.3.4Pharmaceutical form Prolonged-release 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 INNTAPENTADOL HYDROCHLORIDE
    D.3.9.1CAS number 175591-09-0
    D.3.9.2Current sponsor codeCG5503
    D.3.9.3Other descriptive nameTAPENTADOL HYDROCHLORIDE
    D.3.9.4EV Substance CodeSUB32145
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    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
    No medical condition to be investigated.
    E.1.1.1Medical condition in easily understood language
    Not applicable (Chronic Pain)
    E.1.1.2Therapeutic area Diseases [C] - Nervous System Diseases [C10]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 17.0
    E.1.2Level LLT
    E.1.2Classification code 10049475
    E.1.2Term Chronic pain
    E.1.2System Organ Class 100000004867
    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 objective of the trial is to assess the pharmacokinetics and relative bioavailability of tapentadol following administration of 3 prototype tapentadol PR granule formulations (test formulations) each containing 25 mg tapentadol, compared to 1 tablet of Palexia® PR 25 mg (reference formulation) under fasted and fed conditions.

    The main pharmacokinetic target parameters are Cmax and AUC0-t for tapentadol.
    E.2.2Secondary objectives of the trial
    Secondary objectives are to assess the safety, tolerability, and palatability of the tapentadol PR granule formulations.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Subjects have given written informed consent to participate.
    2. White, male, and aged 18 years to 55 years, inclusive.
    3. Body mass index between 18.5 kg/m2 and 30.0 kg/m2, inclusive, with a lower body weight limit of 50.0 kg.
    4. In good health as determined by medical history (including surgical history), physical examination, 12-lead ECG, vital signs, and safety laboratory parameters.
    E.4Principal exclusion criteria
    Exclusion criteria (Enrollment Visit for Part 1 and Part 2)
    1. Resting pulse rate is less than 50 beats or equal and greater than 90 beats per minute after 5 minutes rest in a supine position.
    2. Resting blood pressure after 5 minutes rest in a supine position. Systolic blood pressure is less than 110 mmHg or equal and greater than 140 mmHg. Diastolic blood pressure is less than 60 mmHg or equal and greater than 90 mmHg.
    3. QT or QTcB interval prolongation of greater than 500 ms.
    4 a) Any out-of-reference range value for: gamma-glutamyl transferase, serum creatinine, prothrombin time, and international normalized ratio.
    b) Any exclusion range met for urinalysis and laboratory parameters: alanine transaminase, aspartate transaminase, alkaline phosphatase, total bilirubin, glucose (fasted), lactate dehydrogenase, total protein, creatine kinase, hemoglobin, hematocrit, white blood cell count, and platelets.
    c) Any out-of-reference range value for any other clinical laboratory parameter that is judged as clinically relevant by the investigator.
    5. Evidence for thyroid disease.
    6. History of orthostatic hypotension.
    7. Positive or missing test for human immunodeficiency virus type 1/2 antibodies and antigen, hepatitis B surface antigen and core antibodies, or hepatitis C antibodies.
    8. Participation in another clinical trial within the 30 days before the Enrollment Visit, or a previous IMP within a period less than 10 times its half-life, whichever is longer.
    9. History of drug abuse, or alcohol abuse or has an acute intoxication with centrally acting drugs.
    10. Positive or missing alcohol breath test.
    11. Positive or missing drugs of abuse test.
    12. History of gastric surgery, existing or suspicion of having a paralytic ileus, or current significant medical illness.
    13. History of clinically significant allergies, especially known hypersensitivity/intolerance or contraindications to opioids, opioid antagonists, or any excipients of the drug formulation.
    14. Any contraindication for tapentadol or drugs with mu-opioid receptor agonist activity, i.e., subjects with significant respiratory depression, and subjects with acute or severe bronchial asthma or hypercapnia.
    15. History of seizure disorder, epilepsy, or mild or moderate brain injury, stroke, transient ischemic attack, brain neoplasm within 1 year of enrollment.
    16. Regular use of any prescribed or non-prescribed medications within 14 days before the Enrollment Visit. Use of monoamine oxidase inhibitors within 21 days before the Enrollment Visit.
    17. Not able to abstain from consuming products containing methylxanthine, alcohol, or quinine within 24 hours of the first administration of tapentadol; or Seville oranges or products containing grapefruit juice or poppy seeds within 72 hours of the first administration of tapentadol until discharge from the trial site.
    18. Blood donation or acute loss of blood within 3 months before the Enrollment Visit, or intention to donate blood or blood products during the trial or within 1 month following the completion of the trial.
    19. Known or suspected of not being able to comply with the requirements of the trial protocol.
    20. Not able to communicate meaningfully with the investigator and staff.
    21. Habitually smoking more than 10 cigarettes, 2 cigars, or 2 pipes of tobacco per day within the last 6 months before the Enrollment Visit.
    22. Unable to swallow solid, oral dosage forms whole with the aid of water.
    23. Employee of the investigator or trial center, as well as family members of the employees or the investigator.

    Exclusion criteria (Day -1 Period 1 for Part 1 and Part 2)
    24. Received IMP or an investigational device since the Enrollment Visit.
    25. Any out-of-reference range value for clinical laboratory parameters or any exclusion range met for urinalysis and clinical laboratory parameters as per exclusion criterion 4.
    26. Blood donation or acute loss of blood since the Enrollment Visit.
    27. Regular use of any prescribed or non-prescribed medications since the Enrollment Visit.
    28. Any relevant deterioration in the health of the subject that could alter the benefit/risk assessment for the subject.
    29. Positive or missing alcohol breath test.
    30. Positive or missing drugs of abuse test.
    31. Failure to comply with trial requirements.
    32. Withdrawal of informed consent.
    33. Not able to communicate meaningfully with the investigator and staff.
    34. Consumption of products containing methylxanthine, alcohol, or quinine 24 hours before dosing, or Seville oranges or products containing grapefruit juice or poppy seeds 72 hours before dosing.
    E.5 End points
    E.5.1Primary end point(s)
    No endpoints have been defined for this trial.
    E.5.1.1Timepoint(s) of evaluation of this end point
    No endpoints have been defined for this trial.
    E.5.2Secondary end point(s)
    No endpoints have been defined for this trial.
    E.5.2.1Timepoint(s) of evaluation of this end point
    No endpoints have been defined for this trial.
    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 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 Yes
    E.6.13.1Other scope of the trial description
    Relative Bioavailability Study.
    Pediatric development program that fulfills the requirements of the Paediatric Committee (PDCO) of the European Medicines Agency.
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    Relative bioavailability study
    E.7.2Therapeutic exploratory (Phase II) No
    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 Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over Yes
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    Part 1: fasted condition, Part 2: fed condition
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    marketed tapentadol prolonged release 25 mg tablet formulation
    E.8.2.4Number of treatment arms in the trial4
    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
    LVLS.
    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 months9
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial months9
    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: 48
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female No
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers Yes
    F.3.2Patients No
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    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 state48
    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)
    The trial will be conducted in healthy subjects. Any adverse event or clinically relevant abnormal laboratory or vital sign result must be followed until it reaches a satisfactory resolution, or becomes stable, or clinical judgment indicates that further evaluation is not warranted.
    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 Decision2014-11-03
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2014-11-11
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2015-06-15
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
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