migraine MedDRA version: 12.0 Level: LLT Classification code 10027599 Term: Migraine
Conditions
Interventions
Product Name: Dihydroergotamine Mesylate (DHE) Tempo® Inhaler
Product Code: MAP0004
Pharmaceutical Form: Pressurised inhalation*
INN or Proposed INN: Dihydroergotamine Mesilate
CAS Number: 6190-32-2
Sponsors
MAP Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
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 =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • Compare the pharmacokinetics of Dihydroergotamine Mesylate delivered by oral inhalation (MAP0004) or intravenously (IV) (DHE 45) in smokers versus non-smokers;Secondary Objective: • Identify whether there are clinically significant differences in the tolerability of MAP0004 between smokers and non-smokers;Primary 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 | — |
Countries
United Kingdom
Outcome results
None listed