Pharmacokinetics & Tolerability Study of MAP0004 in Smoking and Non-Smoking Adult Volunteers

Study Overview
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Brief Summary
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Compare the pharmacokinetics of Dihydroergotamine Mesylate (DHE) delivered by oral inhalation (MAP0004) or Intravenous (IV) DHE in smokers versus non-smokers. Identify whether there are clinically significant differences in the tolerability of MAP0004 between smokers and non-smokers.

Official Title
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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

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: MAP0004
* Drug: IV DHE


Participation Criteria
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Eligibility Criteria
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Major Inclusion Criteria: Able to provide written informed consent Male or Female subjects 18 to 45 years old Female subjects who are practicing adequate contraception or who are sterile Stable cardiac status Normal rhythm or arrhythmia deemed clinically insignificant on ECG Major Exclusion Criteria: Contraindication to dihydroergotamine mesylate (DHE) Use of any excluded concomitant medications within the 10 days prior to Visit 1 (See Section 5.5) History of hemiplegic or basilar migraine Participation in another investigational trial during the 30 days prior to Visit 1 or during this trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: IV DHE then MAP0004<br>Smokers and non-smokers received Intravenous Dihydroergotamine Mesylate (IV DHE) at Visit 2 followed by MAP0004 7-11 days later at Visit 3. | Drug: MAP0004<br>* 1.0mg MAP0004 via inhalation at Visit 2 or 3 as per protocol<br>Drug: IV DHE<br>* IV DHE administered at Visit 2 or 3 as per protocol<br>* Other names: D.H.E.45®;|
| Other: MAP0004 then IV DHE<br>Smokers and non-smokers received MAP0004 at Visit 2 followed by Intravenous Dihydroergotamine Mesylate (IV DHE) 7-11 days later at Visit 3. | Drug: MAP0004<br>* 1.0mg MAP0004 via inhalation at Visit 2 or 3 as per protocol<br>Drug: IV DHE<br>* IV DHE administered at Visit 2 or 3 as per protocol<br>* Other names: D.H.E.45®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of Dihydroergotamine After MAP0004 and IV DHE Administration in Smokers Versus Non-smokers | The maximum concentration (Cmax) is the highest concentration of a drug measured in the plasma. Plasma is the clear portion of the blood. The Cmax of Dihydroergotamine is reported in picograms per milliliter (pg/ml). | 48 hours | 
| AUC(0-48) of Dihydroergotamine After MAP0004 and IV DHE Administration in Smokers and Non-smokers | The AUC(0-48) is the area under the plot of plasma concentration of drug against time after drug administration. Dihydroergotamine AUC(0-48) is reported in picograms times hour per milliliter (pg*h/ml). | 48 hours |