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    Summary
    EudraCT Number:2013-002642-37
    Sponsor's Protocol Code Number:B1481019
    National Competent Authority:Poland - Office for Medicinal Products
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2013-12-10
    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 ConcernedPoland - Office for Medicinal Products
    A.2EudraCT number2013-002642-37
    A.3Full title of the trial
    A PHASE 3 DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED, PARALLEL-GROUP STUDY TO ASSESS THE EFFICACY, SAFETY AND TOLERABILITY OF PF-04950615 IN SUBJECTS WITH PRIMARY HYPERLIPIDEMIA OR MIXED DYSLIPIDEMIA AT RISK OF CARDIOVASCULAR EVENTS
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase 3 study investigating the efficacy, safety and tolerability of PF-04950615 in subjects with elevated levels of any or all of the lipids or lipoproteins in the blood who are at risk of developing cardiovascular disease
    A.4.1Sponsor's protocol code numberB1481019
    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 SponsorPfizer Inc., 235 East 42nd Street, New York, NY 10017
    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 supportPfizer Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationPfizer Inc
    B.5.2Functional name of contact pointClinical Trials.gov Call Centre
    B.5.3 Address:
    B.5.3.1Street Address235 East 42nd Street
    B.5.3.2Town/ cityNew York
    B.5.3.3Post codeNY 10017
    B.5.3.4CountryUnited States
    B.5.4Telephone number+18007181021
    B.5.5Fax number+13037391119
    B.5.6E-mailClinicalTrials.gov.CallCentre@pfizer.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.3.2Product code PF-04950615
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNNot applicable
    D.3.9.1CAS number 1407435-02-6
    D.3.9.2Current sponsor codePF-04950615
    D.3.9.3Other descriptive nameRN316
    D.3.9.4EV Substance CodeSUB31542
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    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) Yes
    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 placeboSolution for injection
    D.8.4Route of administration of the placeboSubcutaneous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    primary hyperlipidemia or mixed dyslipidemia
    E.1.1.1Medical condition in easily understood language
    High Cholesterol
    E.1.1.2Therapeutic area Diseases [C] - Cardiovascular Diseases [C14]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.1
    E.1.2Level LLT
    E.1.2Classification code 10020667
    E.1.2Term Hyperlipidemia
    E.1.2System Organ Class 100000004861
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.1
    E.1.2Level LLT
    E.1.2Classification code 10058110
    E.1.2Term Dyslipidemia
    E.1.2System Organ Class 100000004861
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To demonstrate a superior LDL-C lowering effect of PF-04950615 150 mg administered by the SC route Q2wks compared to placebo, in subjects with primary hyperlipidemia or mixed dyslipidemia at high and very high risk for CV events receiving a maximally tolerated dose of statin therapy and whose LDL-C is ≥70 mg/dL (1.81 mmol/L).
    E.2.2Secondary objectives of the trial
    To demonstrate a superior effect of PF-04950615 150 mg administered by the SC route Q2wks compared to placebo, in subjects with dyslipidemia and at high and very high risk for CV events receiving maximally tolerated dose of statin therapy and whose LDL-C is ≥70 mg/dL on total cholesterol , HDL-C, Triglycerides, and non HDL-C;other lipid parameters, including Apolipoprotein B, Apolipoprotein A-I, Apolipoprotein A-II, lipoprotein, very low density lipoprotein cholesteral (VLDL-C)
    To demonstrate a superior LDL-C lowering effect of PF-04950615 150 mg administered by the SC route Q2wks compared to placebo in subjects with primary hypercholesterolemia and mixed dyslipidemia.To compare the safety and tolerability of PF-04950615 150 mg administered by the SC route Q2wks to placebo, in subjects with dyslipidemia at high and very high risk for CV events receiving maximally tolerated dose of statin therapy and whose LDL-C is ≥70 mg/dL
    To assess the immunogenicity and exposure of PF-04950615.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Subject eligibility should be reviewed and documented by an appropriately qualified member of the investigator’s study team before subjects are included in the study.
    Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
    1. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legal representative) has been informed of all pertinent aspects of the study.
    2.Subjects who are willing and able to comply with scheduled visits, treatment plan,laboratory tests, and other study procedures.
    3. Males and females ≥18 years of age; subjects in Korea must be ≥20 years of age.
    4. With primary hyperlipidemia or mixed dyslipidemia.
    5. Subjects are required to be treated with atorvastatin, simvastatin, or rosuvastatin at the highest locally approved dose. If at a lower dose, there must be documentation that the subject is receiving a maximally tolerated dose of the aforementioned statins; and no dose should be lower than atorvastatin 20 mg, rosuvastatin 20 mg, or simvastatin 40 mg.
    -Subjects on simvastatin 80 mg must have been on this dose for >1 year before
    screening.
    - All subjects must be on a stable dose at least 6 weeks prior to screening.There should be no plans at the time of screening and randomization to modify the dose of statin for the duration of the trial.
    -Source records and case report form (CRF) must show documentation of the requirements shown above.
    6. Subjects should be at high or very high risk of incurring a CV event, defined as:
    -Known history of CVD based on any of the below:
    -Coronary heart disease (any one of the following conditions): history of acute myocardial infarction or evidence of silent myocardial infarction or myocardial ischemia, or history of unstable angina or stable angina pectoris,or history of coronary procedures (coronary angioplasty and coronary artery surgery); or
    -Other clinical atherosclerotic diseases (any one of the following conditions): peripheral arterial disease, or abdominal aortic aneurysm, or carotid artery disease (symptomatic [eg, transient ischemic
    attack or stroke of carotid origin] or >50 percent stenosis on angiography or ultrasound), and likely other forms of clinical atherosclerotic disease (eg, renal artery disease). or
    -Type 2 or Type 1 diabetes, or
    -Chronic kidney disease (CKD), defined as glomerular filtration rate (GFR) calculated by Modification of Diet in Renal Disease (MDRD) formula between 30 and 60 mL/min/1.73m2 (inclusive).
    7. Lipids should meet the following criteria on a background treatment with a statin at the 2 screening visits:
    -Subjects at the highest approved dose of statins described in 5, above:
    -Fasting LDL C ≥70 mg/dL (1.81 mmol/L) at both screening visits and the value at the second screening visit within 7 days of randomization must not be lower or higher than 20% of this initial value, as described in Section 7.1 of the protocol
    -Fasting LDL C ≥77 mg/dL (1.99 mmol/L) at both screening visits and the value at the second screening visit within 7 days of randomization must not be lower or higher than 20% of this initial value, as described in Section 7.1 of the protocol
    NOTE: If fasting LDL-C at the second screening visit is lower or higher than 20% of the initial value, LDL-C can be repeted once (within 7 days of randomization), and the subject is eligible if the value of this repeat test is within 20% (inclusive) of the value for the second screening visit.
    -All subjects must have fasting TG ≤400 mg/dL (4.51 mmol/L) at the second screening visit.
    8. Male and female subjects of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 63 days after the last dose of assigned treatment. A subject is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active (Section 4.4.2 of the protocol).
    Female subjects who are not of childbearing potential (ie, meet at least one of the following criteria):
    - Have undergone a documented hysterectomy and/or bilateral oophorectomy;
    - Have medically confirmed ovarian failure or;
    - Achieved post-menopausal status, defined as: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological
    cause; and have a serum follicule-stimulating hormone(FSH) level within the laboratory’s reference range for postmenopausal females.
    E.4Principal exclusion criteria
    Subjects presenting with any of the following will not be included in the study:
    1. Subjects who are investigational site staff members directly involved in the conduct of the trial and their family members, site staff members otherwise supervised by the Investigator, or subjects who are Pfizer employees directly involved in the conduct of the trial.
    2. Participation in other studies involving small molecule investigational drug(s) (Phases 1-4) within 1 month or 5 half lives except for cholesteryl ester transfer protein inhibitors (indefinitely), or biological agents within 6 months or 5 half lives, whichever is longer before the current study begins and/or during study participation (the investigator should refer to documents provided by the subject on the other study to determine the investigational product half life). If the blind has been broken and the Investigator knows (with documentation) that the subject received placebo, he/she can be included.
    3. Subjects with prior exposure to PF-04950615 or other investigational PCSK9 inhibitor.
    4. Subjects who are unable to receive injections, as either a self-injection, or administered by a family member, health care assistant, or health care provider.
    5. History of a cardiovascular or cerebrovascular event or procedure (eg, Myocardial infarction, stroke, transient ischemic attack, angioplasty) during the past 30 days.
    6. Congestive heart failure, New York Heart Association functional class IV, or Left Ventricular Ejection Fraction measured by imaging <25%.
    7. Poorly controlled hypertension at any screening visit or at randomization (defined as the average of two systolic blood pressure measurements greater than 160 mm Hg or the average of two diastolic blood pressure measurements greater than 100 mm Hg, even with treatment). Subjects who have hypertension and are controlled on stable dosages of anti hypertensive medications can be included. An additional blood pressure (BP) measurement may performed within the hour or at the completion of the office visit, to confirm a reading.
    8. Any history of hemorrhagic stroke or lacunar infraction.
    9.Current untreated hypothyroidism or thyroid stimulating hormone (TSH) >1 X upper limit of normal (ULN) at screening. Subjects who are treated and well controlled should be on a stable dose of thyroid hormone for at least 6 months.
    10. Current history of alcoholism or drug addiction according to the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria within 12 months prior to screening. Use of any recreational drugs within 12 months prior to screening.
    11. History of cancer within the last 5 years (except for cutaneous basal cell or squamous cell cancer resolved by excision).
    12. Medical history of positive testing for Human immunodeficiency virus (HIV).
    13. Any disease or condition that might compromise the hematological, renal, hepatic, pulmonary, endocrine, central nervous, immune, or gastrointestinal systems (unless deemed not clinically significant by the Investigator and/or the Sponsor) or confound the interpretation of the study results. Examples of such conditions include but are not limited to nephrotic syndrome, uncontrolled diabetes, excessive alcohol consumption, cholestatic liver disease.
    14. Use of statins other than atorvastatin, rosuvastatin or simvastatin, or use of red yeast rice.
    15. Undergoing apheresis or have planned start of apheresis.
    16. Initiation of, or change in, non lipid lowering prescription drugs, herbal medicine or supplements (including food with added plant sterols and stanols) within 6 weeks of screening (exception: initiation or change in multivitamins used for general health purposes are acceptable). Short term use of medications to treat acute conditions, and vaccines are allowed (e.g., antibiotics or allergy medication.)
    17. Subjects on systemic corticosteroids (ie, oral, intravenous [IV], intramuscular [IM], or
    intra-articular) at screening. The use of topical, inhaled or ophthalmic corticosteroids is permitted.
    18. Subjects taking prescription medications that are contraindicated with the use of statins at screening. Refer to statin product labels for these medications.
    19. History of allergic or anaphylactic reaction to any therapeutic or diagnostic monoclonal antibody (IgG protein) or molecules made of components of monoclonal antibodies (eg, Enbrel® which contains the Fc portion of an antibody or Lucentis® which is a Fab).
    20. Subjects who are latex-sensitive (due to potential for exposure to latex or dry rubber in the pre-filled syringe cap during self administration).
    21. Any abnormal hematology values, clinical chemistries, urinalysis, or ECGs judged by the Investigator as clinically significant, which could impact on subject safety, were the potential subject to be included in the study or interfere with interpretation of the study results.

    For exclusion conditions 22-30 please refer to the protocol.
    E.5 End points
    E.5.1Primary end point(s)
    Percent change from baseline in fasting LDL-C at week 12.
    E.5.1.1Timepoint(s) of evaluation of this end point
    at week 12
    E.5.2Secondary end point(s)
    Key Secondary Endpoints
    -Percent change from baseline in fasting TC, ApoB, and non HDL-C at week 12;
    -Percent change from baseline in fasting LDL-C at week 12 in subjects with primary hyperlipidemia (pre-randomization TG <200 mg/dL (2.26 mmol/L);
    - Percent change from baseline in fasting LDL-C at week 12 in subjects with mixed dyslipidemia (pre-randomization TG <200 mg/dL (2.26 mmol/L);
    - Percent change from baseline in fasting Lp(a) at week 12;
    -Percent change from baseline in fasting HDL-C at week 12.

    Secondary Endpoints
    -Percent change from baseline in fasting LDL-C at week 24 and week 52;
    -Percent change from baseline in fasting LDL-C at week 24 and week 52 by TG cut-off of < or ≥200 mg/dL (2.26 mmol/L);
    -Percent change from baseline in fasting TC, non HDL-C, ApoB, Lp(a) and HDL-C at week 24 and week 52;
    -Percent change from baseline in fasting TG, ApoA-I, ApoA-II at week 12, week 24 and week 52;
    - Absolute change from baseline in fasting LDL-C at week 12 by TG cut-off of < or ≥200 mg/dL (2.26 mmol/L)’;
    - Absolute change from baseline in fasting LDL-C, TC, non HDL-C, TG, Apo B, Lp(a), and HDL-C at week 12
    - Absolute change from baseline in fasting TC/HDL-C ratio and ApoB/ApoA-I ratio at week 12, week 24 and week 52;
    - Percent change from baseline in fasting VLDL-C at Week 12, Week 24 and Week 52;
    - Proportion of subjects achieving fasting LDL-C ≤100 mg/dL (2.59 mmol/L) at week 12,week 24 and week 52;
    - Proportion of subjects achieving fasting LDL-C ≤70 mg/dL (1.81 mmol/L) at week 12, week 24 and week 52;
    - Plasma PF-04950615 concentrations at week 12, week 24 and week 52;
    Safety endpoints are:
    - Adverse events (including Type 1 and 3 hypersensitivity reactions and injection site reactions);
    - Incidence of anti-drug-antibodies.
    E.5.2.1Timepoint(s) of evaluation of this end point
    at weeks 12, 24 and 52
    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 Yes
    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 Yes
    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 concerned14
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA28
    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
    Australia
    Canada
    Czech Republic
    Germany
    Hong Kong
    Italy
    Korea, Republic of
    Poland
    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
    End of Trial in a Member State (MS) of the EU is defined as the time at which it is deemed that sufficient subjects have been recruited and completed the study as stated in the regulatory application and ethics application in the Member State. Poor recruitment by a MS is not a reason for premature termination but is considered a normal conclusion to the study in that Member State. For all other participating countries it is defined as LSLV.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months2
    E.8.9.1In the Member State concerned days26
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months4
    E.8.9.2In all countries concerned by the trial days13
    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: 330
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 270
    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 state98
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 130
    F.4.2.2In the whole clinical trial 600
    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 Decision2014-01-29
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2013-12-10
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2016-04-05
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