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    Summary
    EudraCT Number:2009-016732-12
    Sponsor's Protocol Code Number:MAP0004-CL-P203
    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:2010-03-17
    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 number2009-016732-12
    A.3Full title of the trial
    An Open-Label, 2-Period, Crossover Phase 2 Study Comparing the Pharmacokinetics and Tolerability of Dihydroergotamine Mesylate (DHE) Delivered Intravenously (DHE 45) and by Oral Inhalation (MAP0004) in Smoking and Non-Smoking Adult Volunteers
    A.4.1Sponsor's protocol code numberMAP0004-CL-P203
    A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorMAP Pharmaceuticals, Inc.
    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 support
    B.4.2Country
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    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 nameDihydroergotamine Mesylate (DHE) Tempo® Inhaler
    D.3.2Product code MAP0004
    D.3.4Pharmaceutical form Pressurised inhalation*
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPInhalation use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNDihydroergotamine Mesilate
    D.3.9.1CAS number 6190-32-2
    D.3.9.2Current sponsor codeMAP0004
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1.0
    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) Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    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 Information not present in EudraCT
    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 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 D.H.E. 45® (dihydroergotamine mesylate) Injection, USP
    D.2.1.1.2Name of the Marketing Authorisation holderValeant Pharmaceuticals North America
    D.2.1.2Country which granted the Marketing AuthorisationUnited States
    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 nameD.H.E. 45® (dihydroergotamine mesylate) Injection, USP
    D.3.4Pharmaceutical form Injection*
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    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 INNDIHYDROERGOTAMINE MESILATE
    D.3.9.1CAS number 6190-39-2
    D.3.9.3Other descriptive nameDIHYDROERGOTAMINE MESILATE
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1.0
    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) Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    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 Information not present in EudraCT
    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
    migraine
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 12.0
    E.1.2Level LLT
    E.1.2Classification code 10027599
    E.1.2Term Migraine
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    • Compare the pharmacokinetics of Dihydroergotamine Mesylate delivered by oral inhalation (MAP0004) or intravenously (IV) (DHE 45) in smokers versus non-smokers
    E.2.2Secondary objectives of the trial
    • Identify whether there are clinically significant differences in the tolerability of MAP0004 between smokers and non-smokers
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Able to provide written informed consent
    2. Male or Female subjects 18 to 45 years old
    3. Female subjects who are practicing adequate contraception or who are sterile
    4. Stable cardiac status
    5. Normal rhythm or arrhythmia deemed clinically insignificant on ECG
    6. Heart rate ≥ 40 and ≤ 100 at Visit 1 vital signs assessment (resting)
    7. QTcF (Fridericia’s Correction) ≤ 450 msec
    8. Non smokers: never smoked or total exposure <1 pack year and at least 12 months since last
    cigarette with a negative urinary cotinine result at screening
    9. Smokers: currently smoking at least 10 cigarettes/day for at least 1 year with a positive
    urinary cotinine result at screening
    10. Demonstrated ability to properly use the Tempo® Inhaler
    E.4Principal exclusion criteria
    1. Contraindication to dihydroergotamine mesylate (DHE)
    2. Use of any excluded concomitant medications within the 10 days prior to Visit 1
    3. History of hemiplegic or basilar migraine
    4. Participation in another investigational trial during the 30 days prior to Visit 1 or during this trial
    5. Diagnosis of cancer (other than a non-invasive skin cancer) within the 5 years prior to Visit 1
    6. Major surgery, vascular surgery or sepsis during the 6 months prior to Visit 1 (major surgery is defined as any surgery requiring general anesthesia and hospitalization for ≥ 2 days post operatively)
    7. History of unstable psychiatric illness requiring medication or hospitalization in the 12 months leading up to Visit 1
    8. Subjects who have known allergy or sensitivity to study drugs or their formulations
    9. Women who are pregnant, breast feeding or plan a pregnancy during this trial
    10. Clinically significant liver (any/all of SGPT > 150U/L; SGOT > 130 U/L or LDH > 750 U/L) or kidney disease (serum creatinine > 4.0 mg/dL)
    11. History of chronic pulmonary disease
    12. History of coronary artery disease (CAD), coronary vasospasm (including Prinzmetal’s angina), aortic aneurysm, peripheral vascular disease or other ischemic diseases (e.g., ischemic bowel syndrome or Raynaud’s syndrome)
    13. The following CAD risk factor:
    • Hypertension (systolic BP > 140 or diastolic BP > 90)
    Or any 2 of the following 4 CAD risk factors:
    • Receiving anti hypertensive medication for the treatment of hypertension.
    • Hyperlipidemia – (LDL) > 159 mg/dL and/or (HDL) < 40 mg/dL (or on prescribed anti
    cholesterol treatment)
    • Family history of premature coronary artery disease (CAD) (< 55 years of age in male first
    degree relatives or < 65 years of age in female first degree relatives)
    • Diabetes mellitus
    14. History of cerebral vascular accident (CVA), transient ischemic attacks (TIA), or seizures
    15. History of concurrent illness that requires hospitalization within the 30 days prior to Visit 1
    16. History of bronchospasm with any inhaled medication or other inhaled substance, such as CFC or HFA propellants
    17. Subjects who have received other diagnostic or research radiation exposure in the last 12 months, with the exception of routine dental x-rays
    18. Any condition that, in the opinion of the Investigator, would make the subject unsuitable for study participation and completion, including but not limited to:
    • Any reason to believe that compliance with the study requirements and completion of evaluations required for this study will not be possible
    • Any language barrier that, in the opinion of the Investigator, would preclude
    communication and compliance with the study requirements
    • History or current abuse or dependence on alcohol or drugs that would interfere with adherence to study requirements
    • Any clinically relevant abnormal findings in the physical exam, vital signs or laboratory tests that, in the opinion of the Investigator, may put the subject at risk
    E.5 End points
    E.5.1Primary end point(s)
    The Primary Endpoints to be measured in this study are DHE and metabolite of DHE, namely 8’ OH DHE levels as follows:
    • Cmax: maximal plasma concentration
    • Tmax: time at which maximal plasma concentration is observed
    • AUC 0-48: area under the plasma concentration versus time curve, as determined by a trapezoidal method, from time zero to 48 hours post-dose.
    • AUC 0-inf: area under the plasma concentration versus time curve, from time zero to time infinity.
    • T1/2: elimination half-life of DHE parent drug from the plasma

    The Secondary Endpoints to be measured in this study are as follows:
    • Clinical AEs
    • Laboratory evaluations
    • Vital signs
    • ECG
    • FEV1
    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 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 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 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.8.3 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 Information not present in EudraCT
    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
    The end of the trial is the last subject's last visit.
    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 months2
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years0
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    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.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    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 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)
    This is a healthy volunteer study. No treatment or care will be provided after the subject has ended his/her participation in the trial.
    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 Decision2010-01-21
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2009-11-13
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2010-04-16
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    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
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